美國專科藥師認證經驗與臨床藥事照護案例分享(BCCCP急重症加護專科)
臺北榮總藥學部 臨床藥學科 陳佳慧藥師
20190905
Taipei Veterans General Hospital
Outline
bull Preparation for Critical care pharmacy specialist certification
bull Experiences of clinical pharmacy services in ICU
Taipei Veterans General Hospital
Critical Care Pharmacy Specialist Certification Content Outline
bull Domains
bull Clinical Knowledge and Application (65 percent of examination)
bull Practice Management Policy and Quality Improvement (15 percent of examination)
bull Evidence-Based Medicine Scholarship Education and Professional Development (20 percent of examination)
Taipei Veterans General Hospital
10 Sections (51 chapters)
bull Supportive care
bull Infectious disease
bull Neurocritical care
bull Hematology
bull Acute kidney injury
bull LiverGastrointestinal
bull Acute pulmonary disease
bull Cardiovascular critical care
bull Other Emergencies
bull Miscellaneous
ISBN 978-1-939862-20-4 2016 1072 pages
Price PrinteBook ($12995 member $10995)
Taipei Veterans General Hospital
The workbook includes
bull Chapters offering a comprehensive review of the full scope of Critical Care Pharmacy
bull Over 200 patient cases with explained answers to enhance your case based learning
bull Over 200 self-assessment questions with explained answers
bull Current and relevant references at the end of each chapter
Release date May 15 2019
Workbook Price
bull Print $275 member $175
bull Online (printable pdf) $265 member $165
Audio-synchronized slide presentations available online
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Outline
bull Preparation for Critical care pharmacy specialist certification
bull Experiences of clinical pharmacy services in ICU
Taipei Veterans General Hospital
Critical Care Pharmacy Specialist Certification Content Outline
bull Domains
bull Clinical Knowledge and Application (65 percent of examination)
bull Practice Management Policy and Quality Improvement (15 percent of examination)
bull Evidence-Based Medicine Scholarship Education and Professional Development (20 percent of examination)
Taipei Veterans General Hospital
10 Sections (51 chapters)
bull Supportive care
bull Infectious disease
bull Neurocritical care
bull Hematology
bull Acute kidney injury
bull LiverGastrointestinal
bull Acute pulmonary disease
bull Cardiovascular critical care
bull Other Emergencies
bull Miscellaneous
ISBN 978-1-939862-20-4 2016 1072 pages
Price PrinteBook ($12995 member $10995)
Taipei Veterans General Hospital
The workbook includes
bull Chapters offering a comprehensive review of the full scope of Critical Care Pharmacy
bull Over 200 patient cases with explained answers to enhance your case based learning
bull Over 200 self-assessment questions with explained answers
bull Current and relevant references at the end of each chapter
Release date May 15 2019
Workbook Price
bull Print $275 member $175
bull Online (printable pdf) $265 member $165
Audio-synchronized slide presentations available online
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Critical Care Pharmacy Specialist Certification Content Outline
bull Domains
bull Clinical Knowledge and Application (65 percent of examination)
bull Practice Management Policy and Quality Improvement (15 percent of examination)
bull Evidence-Based Medicine Scholarship Education and Professional Development (20 percent of examination)
Taipei Veterans General Hospital
10 Sections (51 chapters)
bull Supportive care
bull Infectious disease
bull Neurocritical care
bull Hematology
bull Acute kidney injury
bull LiverGastrointestinal
bull Acute pulmonary disease
bull Cardiovascular critical care
bull Other Emergencies
bull Miscellaneous
ISBN 978-1-939862-20-4 2016 1072 pages
Price PrinteBook ($12995 member $10995)
Taipei Veterans General Hospital
The workbook includes
bull Chapters offering a comprehensive review of the full scope of Critical Care Pharmacy
bull Over 200 patient cases with explained answers to enhance your case based learning
bull Over 200 self-assessment questions with explained answers
bull Current and relevant references at the end of each chapter
Release date May 15 2019
Workbook Price
bull Print $275 member $175
bull Online (printable pdf) $265 member $165
Audio-synchronized slide presentations available online
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
10 Sections (51 chapters)
bull Supportive care
bull Infectious disease
bull Neurocritical care
bull Hematology
bull Acute kidney injury
bull LiverGastrointestinal
bull Acute pulmonary disease
bull Cardiovascular critical care
bull Other Emergencies
bull Miscellaneous
ISBN 978-1-939862-20-4 2016 1072 pages
Price PrinteBook ($12995 member $10995)
Taipei Veterans General Hospital
The workbook includes
bull Chapters offering a comprehensive review of the full scope of Critical Care Pharmacy
bull Over 200 patient cases with explained answers to enhance your case based learning
bull Over 200 self-assessment questions with explained answers
bull Current and relevant references at the end of each chapter
Release date May 15 2019
Workbook Price
bull Print $275 member $175
bull Online (printable pdf) $265 member $165
Audio-synchronized slide presentations available online
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
The workbook includes
bull Chapters offering a comprehensive review of the full scope of Critical Care Pharmacy
bull Over 200 patient cases with explained answers to enhance your case based learning
bull Over 200 self-assessment questions with explained answers
bull Current and relevant references at the end of each chapter
Release date May 15 2019
Workbook Price
bull Print $275 member $175
bull Online (printable pdf) $265 member $165
Audio-synchronized slide presentations available online
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
ICU藥師參與臨床服務項目
bull Morning meeting
bull Ward round with doctors
bull 一位臨床藥師搭配一位主治醫師每日直接照顧約15床病人
bull 用藥合理性評估
bull Medication reconciliation
bull 建議用藥SOAP
bull Medication Error
bull Therapeutic Drug Monitoring
bull 藥物諮詢
bull ADR通報
bull 教學研究及文章發表
bull 跟診(每週1次)
bull 參與會議
bull 跨領域主任總查房臨床教學暨超其住院病人討論會議 (每週1次)
bull 期刊學術討論會議 (每週1-2次)
bull 死亡臨床病例討論會 (每月2-3例)
bull 重症Grand round (每2月1次)
Everyday 其他
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Critical Thinking Skills
Adam M et al American Journal of Pharmaceutical Education 2019 83 Article 7033
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Cases Discussion
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
bull Pneumonia related septic shock with respiratory failure sp ETT+MV
bull BAL yeast (+) under voriconazole empirical Abx with imipenem+teicoplanin
bull Anti-Glomerulus membrane disease with RPGN in ESRD sp renal transplant on 951021 in China under tacrolimus prednisolone and mycophenolic acid Complicated hematuria acute allograft kidney cellular rejection -sp MTP pulse therapy (500mg qd x3) x2 sp HD
WBC 13800 CRP 214 PCT 07 PLT 125000 Scr 315 Na 138 K 46
DDI voriconazole+tacrolimus
bull Voriconazole may increase the serum concentration of tacrolimus
Case 1Ms H 63 yo 148 cm 419 kg
S
O
A
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Mycophenolic acid tab 180 mg 1 PO QD
Prednisolone tab 5 mg 1 PO QD
Methylprednisolone inj 3125 mg IVA Q12H
Tazocinreg inj 225 g IVA Q8HV
Sevatrimreg inj 5 ml 4 amp IVA QD
Bacidereg tab 400 mg 1 PO Q12H
Tienam 1000 mg IVA Q12H
Teicoplanin inj 600 mg IVA QO
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
Midazolam tab 75 mg 1 PO QN
Propofol inj 500 mg50 ml 3 BOT IVD Q8H
TDM of Tacrolimus 31 35 60 76 46 72 17 379206 71 67
Q8H Q12Htab 4 mg BIDCC
1Q12H
1QD 1
QN
1Q12H
2 BIW14
1QD
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Study design A retrospective pharmacokinetic study
Study population
bull Recipients of allogeneic HSCT who had already been on a steady dose of oral tacrolimus and were started on oral voriconazole for the treatment or prophylaxis of aspergillosis
bull 25 patients were evaluable and retrospectively evaluated
Methods Determination of the concentrationdose (CD) ratio of tacrolimus before and after receiving voriconazole
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital12
Case 1
Dosage of Tacrolimus
bull Before Voricoanzole 1 mg 1 QD + 05 mg 1 QN = 15 mgday
bull After adding Voriconazole 1 mg 1 Q12H = 2 mgday
bull Recommendation 13 of original dosage = 05 mgdayfollowed with frequent monitoring of the tacrolimus blood levels
bull DC tacrolimus till TDM level return to target
bull Shift voriconazole to anidulafungin inj 100 mg qd
DrugdoseroutefrequencyAugust September
11 14 17 20 23 26 29 1 3 5 7 9 11 13 15 17
Tacrolimus cap 1 mg 1 PO Q12H
Tacrolimus cap 05 mg 05 PO QD
Voriconazole tab 200 mg 1 PO Q12H
Anidulafungin inj 100 mg IVA QD
TDM of Tacrolimus 31 35 60 76 46 72 17 379 206 71 67
1 Q12H 1 QD
1 QN
1 Q12H
1 QD
P
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Case 2
Mr T 68 yo 175 cm 688 kg
bull Liver cirrhosis suspect HCV and alcohol related Child Pugh classification C (score 11)
bull He was admitted for liver transplantation (schedule OP date 1130)
bull Transfer to ICU on 1129 due to respiratory failure sp ETT+MV suspect aspiration pneumonia related
bull Acute on chronic renal failure suspect hepatorenal syndrome under midodrine 25 mg bid
bull WBC 11300 CRP 197 PCT 066 PLT 25000 BUN 100 Scr 175(1118)-gt238(1128) TB 752 (1118)-gt1217(1128) ALT 45
bull Na 139 K 41
S
O
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Drugs Dosage Route Frequency Duration
Tazocinreg inj 225 g 225 g IVA Q6H 1129-
Aminopoly-Hreg inj 500 ml (AA 7) 1 BOT IVD QD 1117-
Diltiazem (Herbesserreg ) tab 30 mg 1 TAB PO TID 1120-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 1130-
Furosemide (Lasixreg ) inj 20 mg1ml 1 AMP IVA Q12H 1129-
Insulin aspart (Novorapidreg ) inj 100uml 666 IU SC TIDAC 1117-
Insulin detemir (Levemirreg ) inj 100uml 10 IU SC QN 1117-
Midodrine (Midorinereg ) tab 25 mg 1 TAB PO BID 1124-
Spironolactone (Spirotonereg ) tab 25 mg 2 TAB PO TID 1117-
Ursodeoxycholic (Ursolicreg ) tab 100 mg 1 TAB PO TID 1117-
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General HospitalNassar Junior AP et al PLoS One 2014
Adverse eventsMortality rates at 30 days
AASLD guideline 2012 recommendationsAlbumin infusion plus administration of norepinephrine should also be considered in the treatment of type I hepatorenal syndrome when the patient is in the intensive care unit (Class IIa Level A)
Nassar Junior AP et al PLoS One 2014
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Case 2bull Reassess the treatment of
type 1 hepatorenal syndrome
bull Insufficient dosage of midodrine for hepatorenalsyndrome
bull Please consider to DC midodrine and add norepinephrine 05-3 mghr+ albumin 1 gkg (70 g) on the first day then 20-40 gday
bull Please monitor vital signs renalhepatic function
A
P
Date
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Case 3Mrs C 81 yo 150 cm 775 kg
bull Active problem
bull Left upper pole renal tumor in favor of renal cell carcinoma
bull Pyuria
bull Underlying disease
bull Type 2 DM HTN Af Heart failure COPD
bull Smoking(-) alcohol(-) drug allergy(-)
S O Urine routine 54 RBC 11-20 WBC 4+ squamous epi 3-5 pH 60 protein 10057 RBC 1+ WBC 4+ squamous epi21-35 pH 55 protein 100516 RBC 1+ WBC 4+ squamous epi6-10 pH 55 protein 100
Urine culture 503 GNB 20000ml GPC 30000ml507 Enterococcus faecium 2000ml yeast 5000ml516 Candida tropicalis
Sputum culture513 Acinetobacter baumanniicomplex
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
bull Lab dataBUN7-20
Scr05-12
Ccrgt60
ALT0-40
TB02-16
CRP0-05
ALB38-51
0506 35 141 346 lt5 096 355 38
0510 41 101 488 9 038 446 -
0516 45 090 538 18 031 419 35
0524 46 071 682 22 - 154 40
Na135-147
K34-47
WBC4500-11000
Hb14-18
PLT15k-35k
Glu65-115
0506 137 37 23900 152 128000 204
0510 139 33 15500 112 138000 257
0516 148 47 16600 112 367000 -
0524 147 35 21000 101 253000 -
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Drug ProfileDrugs Dosage Route Frequency Duration
Cefazolin (Veterinreg ) inj 1000 mg 1000 mg IVA Q12H 20180503-0505
Piperacillintazobactam (Tazocinreg ) inj 225 g 45 g IVD Q6H 20180505-0514
Cefoperazonesulbactam (Brosymreg ) inj 1 g 2000 mg IVA Q12H 20180514-
Teicoplanin (Targocidreg ) inj 400 mg 600 mg IVA QD 20180510-0521
Anidulafungin (Erasixreg ) inj 100 mg 100 mg IVA QD 20180516-
Fentanylreg inj 01 mg2ml 1 AMP IVD Q2HPRN 20180506-
Midazolam (Dormicumreg ) inj 5 mg5ml 1 AMP IVD Q2HPRN 20180506-
Pantoprazole (Pantolocreg ) inj 40 mg 40 mg IVA QD 20180506-
Esomeprazole (Nexiumreg ) tab 40 mg 1 TAB NGT QD 20180509-
Furosemide (Lasixreg ) inj 20 mg2ml 1 AMP IVA Q12H 20180507-0510
Insulin aspart 3070 (Novomix 30 FlexPenreg ) 1077 IU SC TIDAC 20180503-
Insulin glargine (Toujeoreg ) 15 IU SC HS 20180503-
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Clinical Evaluation
CandiduriaRepeat culture of mid-stream urine sample
Candida (+)
Candida (-)
Asymptomatic
Symptomatic
Previous healthy pt
Predisposed outpatient
Predisposed inpatient
ObservationManage predisposing
conditions
Evidence for disseminated candidiasisUnstableneutropenic pt
Treatment
Treatment
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Management for Candiduriabull Discontinuation of catheter
bull Medications
bull Fluconazole 200 mgday IV for 7-14 days (not Cglabrata or C krusei)
bull Amphotericin B deoxycholate 03-10 mgkgday IV for 1-7 days
bull Flucytocine 25 mgkg qid PO (alternative choice for Cglabrata)
bull Amphotericin B bladder irrigation highly effective in eradication of Candida cystitis but the effect is transient
bull Surgery Strongly recommended for urinary fungus balls
IDSA Infectious Diseases Association of America
Drug of Choice
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Pharmacokinetic Parameters of Echinocandins
VariableCaspofunginCancidasreg
MicafunginMycaminereg
AnidulafunginErasixreg
T12 (hrs) 9-11 11-17 24-26
Vd (Lkg) 014 (967L) 0215-0242 05 (30-50 L)
AUC (mghL) 879-1148 1113 444-53
Protein binding () 96-97 998 84
Metabolism Via slow peptide hydrolysis and N-acetylation Also spontaneously degrades to inactive product
Via catechol-O-methyltransferase pathway
Not metabolised undergoes slow chemical degradation to inactive metabolites
Elimination 35 feces 41 urine (sim14 as unchanged drug)
40 feces lt15 urine(lt 1 as unchanged drug)
Primarily in feces (lt10 as intact drug) 1 urine
Dosage adjustment in renal insufficiency
No dose adjustment needed
No dose adjustment needed
No dose adjustment needed
Dosage adjustment in hepatic insufficiency
Child-Pugh class BC70 mg on day 1 followed by 35 mg once daily
No dose adjustment needed
No dose adjustment needed
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
Evidences of Echinocandins for CandiduriaResearch Caspofungin (Cancidasreg ) Micafungin (Mycaminereg )
Sobel JD et al Clin Infect Dis 2007(Case series)
bull 6 pts with significant candiduriabull 3 cases secondary to hematogenous
renal candidiasis were promptly eradicated
bull 3 cases of complicated ascending candida glabrata infection successfully treated
Schelenz SBMC Infect Dis 2006(Case report)
A case of obstructive pyonephrosis due to candida glabrata strain that failed to respond to intravenous treatment with caspofungin
Kane LE Muzevich KMMed Mycol Case Rep 2016(Case series)
5 cases with candiduria had resolution of baseline fungal with micafungin treated for a minimum of 6 days
Gabardi S et alInt Urol Nephrol 2016(Retrospective analysis)
bull 16 cases with candiduria (C albican39 C kruseiampglarata 33)
bull Short- and long-term urine sterilization
Grau S et alInt J Antimicrob Agents 2016 (Case series)
4 of 6 cases with fluconazole-resistant Candida spp UTI successfully treated
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
bull Suboptimal selection of anidulafungin concentration of urine lt1
bull Please switch anidulafungin to fluconazole 200 mg qdIVA
bull Please monitor fluconazole related side effects such as hepatotoxicity and prolonged Q-T interval on ECG etc
bull Please monitor vital signs infection signs and renalhepatic function
A
P
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
Taipei Veterans General Hospital
After Certification 重症Grand round
海外經驗分享教學~
Taipei Veterans General Hospital
Thank You
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