Antibiotic therapy for Pneumonia in the ICU

OutlinePneumonia dan Pneumonia beratPeta Kuman RSAntibiotik untuk PneumoniaKombinasi antibiotik untuk pneumonia

PneumoniaPneumonia: Radang paru yang disebabkan oleh bakteri dengan gejala panas tinggi disertai batuk berdahak, napas cepat (frekuensi nafas >50 kali/menit), sesak, dan gejala lainnya (sakitkepala, gelisah dan nafsu makan berkurang) Riskesdas 2013

Epidemiologi Pneumonia di IndonesiaPrevalensi Pneumonia di 2013: 4,5%Grafik perbandingan period prevalence 2007 vs 2013Riskesdas 2013

Kasus Pneumonia yang dirawat di ICUCAP beratHCAP beratHAP onset dini, tetapi beratHAP late onsetVAP

Komplikasi terkait CAPPediatric Community Pneumonia Guidelines d CID 2011:53 (1 October) d e28

Kriteria CAP berat pada pasien anakPediatric Community Pneumonia Guidelines d CID 2011:53 (1 October) d e28

Kriteria CAP berat pada pasien dewasaIDSA/ATS Guidelines for CAP in Adults CID 2007:44 (Suppl 2) S27

Mortality, Hospital and ICU Stay Pneumonia Patients with VAP vs Non VAP Esperatti M, et al. Am J Respir Crit Care Med Vol 182. pp 15331539, 2010

ParametersPatients with VAPPatients Non-VAPHospital Stay (days)4141ICU Stay (days)2418Mortality42%36%

Mikroorganisme Penyebab Pneumonia Derajat BeratCurr Opin Pulm Med.2012;18(3):213-221.

Faktor risiko Patogen multiresisten menyebabkan HAP, HCAP, dan VAPAmerican Journal of Respiratory and Critical Care Medicine Vol 171 2005

Pola Kuman ICU RS Persahabatan 2014

P. aeruginosaP aeruginosa has emerged as the epitome of MDR gram-negative bacilli causing hospital-acquired pneumonia (HAP). Possesses at least five distinct mechanisms for inducing antibiotic resistance

Antibiotik untuk PneumoniaEarly, appropriate, broad-spectrum antibiotics in adequate doses, while avoiding excessive antibiotics by de-escalation of initial antibiotic therapy, based on microbiologic cultures and the clinical response of the patient, and shortening the duration of therapy to the minimum effective period.An empiric therapy regimen should include agents that are from a different antibiotic class than the patient has recently received.Combination therapy for a specific pathogen should be used judiciously in the therapy of HAP, and consideration should be given to short-duration (5 days) aminoglycoside therapy, when used in combination with a -lactam to treat P. aeruginosa pneumonia.American Journal of Respiratory and Critical Care Medicine Vol 171 2005

Faktor yang harus dipertimbangkan dalam pemberian antibiotikData mikrobiologiMonoterapi vs kombinasi terapiDosis obatPenetrasiWaktu ToksisitasRisiko ResisitensiPemakaian antibiotik sebelumnyaCost effectiveness

Kollef MH. Clin Infect Dis 2000;31(suppl 4): S131-S138 Ibrahim EH et al. Chest 2000; 118:146-155*

What factors should be considered when choosing an antibiotic?Mandell et al. Clin Infect Dis 2007; 44: S2772Woodheadet al. Clin Microbiol Infect 2011; 17(Suppl 6): E1E59Lim et al. Thorax 2009: 64 (Suppl 3): iii1iii55

Resistance Potential: All Antibiotics Are Not the SameCunha BA. Semin Respir Infect. 2002;17:231-239.

AntibioticAnti-P. aeruginosa ActivityP. aeruginosa Resistance PotentialPiperacillin-tazobactamCeftazidimeCefepimeImipenemMeropenemGentamicinAmikacinLevofloxacinCiprofloxacin+++++++++++++++++++++++++++++++++++++++++++++++++

2011 European Respiratory Society guidelinesWoodhead et al. Clin Microbiol Infect 2011; 17(Suppl 6): E1E59 #Antibiotic must be effective against S. pneumoniae within the fluroquniolones moxifloxacin has highest anti-pneumococcal activity

Adherence to guidelines and CAP outcome (length of stay)Prospective observational study of 780 ptsShorter length of stay in pts receiving adherent regimens (7.6 vs 10.4days

Dambrava PG, et al, Eur Respir J 2008; 32:892-901

Adherence to guidelines and CAP outcome (mortality)mortality less in pts that received adherent regimens (3% vs 10.6%)

Dambrava PG, et al, Eur Respir J 2008; 32:892-901

Risk factors associated with early deathGarcia-Vidal C, et al, Eur Respir J 2008; 32:733-739Odds Ratio (multivariate analysis)

Early initiation of appropriate antibiotic therapy for septic shock and survival

Deresinski S Clin Infect Dis. 2007;45:S177-S183

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Survival fraction0.840.780.70.620.580.50.420.360.270.180.090.06

Cumulative effective antimicrobial initiation0.080.160.260.360.40.460.50.620.70.840.881

Category 33.51.83

Category 44.52.85

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Survival of CAP patients with early ICU admission vs late admission

Retrospective cohort study of 161 CAP ICU patients MVA using Cox proportional hazard modelPrimary outcome: 30-day mortality adjusted for severity Late ICU-admitted patients had a 30-day mortality (47.4%) compared with early admitted patients (23.2%) (P=0.02)Similar result after adjusting in MVA (HR 2.6; 95% CI 1.2-5.5; P=0.02) Restrepo M I et al. Chest 2010; 137:552-557EUCUA (Direct or 2d)Time to death at 30 daysCumulative Survival

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2007 ATS-IDSA guidelines ICUMandell LA, et al. Clin Infect Dis 2007; 44: S27-72CAP Inpatient TherapyIntensive Care UnitNo Pseudomonas RiskNo b-lactam AllergyPseudomonas Riskb-lactam Allergy b-lactam + Either advanced macrolide ORRespiratory FluoroquinoloneRespiratory Fluoroquinolone + AztreonamNo b-lactam Allergyb-lactam AllergyAnti-pseudomonal, antipneumococcal b-lactam / carbapenem + Cipro / Levo 750 ORAnti-pseudomonal, antipneumoccal b-lactam / carbapenem + Aninoglycoside + AzithromycinAztreonam+ Respiratory Fluoroquinolone + Aminoglycoside

Terapi AntibiotikSemua Terapi Awal Empirik, pilihan mencakup > 90% patogen penyebab, perhitungkan pola resistensi setempat Pada kasus berat, butuh dosis dan cara pemberian adekuat. Terapi IV, sulih terapi bila klinis dan saluran cerna baikDe-eskalasi setelah ada hasil kultur dari sal nafas bawah dan perbaikan klinisKombinasi AB bila kemungkinan MDRJangan mengganti sebelum 72 jam, kecuali klinis memburukData mikroba dan sensitivitas untuk mengubah pilihan empirik apabila klinis awal tidak memuaskan

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Non MDR : S. pneumonia, H.influenza, MSSABacteria classified as MDR Pathogens are: Pseudomonas aeruginosa MRSA, Acinetobacter spp.EnterobacteriaceaeEnterobacteriaceaeEnterobacter spp. ESBL-positive strains Klebsiella spp.LegionellapneumophilaBurkholderiacepaciaAspergillus spp.

Benefit of Combination therapy?Sinergi in VitroMengcover sebagian besar jenis kumanMempercepat deeskalasiMempercepat kesembuhanMemperpendek lama perawatanMunurunkan biaya rawat inap

Benefit of combination therapyHad activity against the major causes of CAP, including drug-resistant Streptococcus pneumoniaEvidences showed the superiority of combination therapy compared with monotherapy for subset population (severe CAP, bacteremic penumococcal CAP, intubated CAP)

Studi yang mendukung kombinasi antibiotik vs monoterapi untuk CAPAnn Intensive Care. 2011; 1: 48.

Studi yang mendukung kombinasi antibiotik vs monoterapi untuk CAP (2)Ann Intensive Care. 2011; 1: 48.

Studi di mana tidak ada perbedaan bermakna kombinasi antibiotik vs monoterapi untuk CAPAnn Intensive Care. 2011; 1: 48.

RisksDo the patient had comorbid disease?Renal impairment do dose adjustmentHepatic impairment choose non-excreted drugs via hepatic and biliaryQ-T interval prolongation caution with fluoroquinolone drugsDM

Do patient had drug allergy?Ask the patient if they had drug(s) allergyChange to not allergy drug (s)Think about cross reactivity penicillin allergy to cephalosporin drug (?)

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What are the choices of the combination?When to use this combination considering the risk and benefit? (refer to Levo-Meropenem)

ATSD & IDSA 2004 RecommendationsInitial EMPIRIC therapy for HAP, CAP, and HCAP in patients with late-onset disease or risk factor for MDR pathogens and all disease severityIf an ESBL+ strain, such as K. pneumoniae, or an Acinetobacter species is suspected, a carbepenem is a reliable choice. If L. pneumophila is suspected, the combination antibiotic regimen should include a macrolide (e.g. azithromycin) or a fluoroquinolone (e.g. levofloxacin or ciprofloxacin) should be used rather than an aminoglycosideLevofloxacin 750mg q12h, ciprofloxacin 400mg q8hIf MRSA risk factors are present or there is a high incidence locally

Potential PathogenRecommended AntibioticPathogens listed in previous table and MDR pathogens P. aeruginosa K. pneumoniae (ESBL+)1 Acinetobacter species1

MRSA Legionella pneumophila1Antipseudomonal cephalosporin(cefipime, ceftazidime) orAntipseudomonal carbepenem(imipenem or meropenem) or-Lactam/-lactamase inhibitor(piperacillin-tazobactam) plusAntipseudomonal Fluroquinolone1(Levofloxacin or ciprofloxacin)2 orAminoglycoside(amikacin, gentamicin, or tobramycin) plusLinezolid or vancomycin3

Initial empiric therapy in patients with late onset or risk factors for MDR pathogens, and any disease severityPathogens listed previously (S. pneumoniae, H. influenzae, MSSA, antibiotic-susceptible EGNB)

MDR pathogensP. aeruginosaK. pneumoniae ESBLAcinetobacter spp.MRSA

Anti-pseudomonal cephalosporin (cefepime, ceftazidime) OR anti-pseudomonal carbapenem (imipenem or meropenem) OR -lactam/-lactamase inhibitor (piperacillin/tazobactam)PLUSAnti-pseudomonal fluoroquinolone (ciprofloxacin or levofloxacin) OR aminoglycoside (amikacin, gentamicin or tobramycin)PLUS Linezolid or vancomycin (if MRSA risk factors are present or there is a high incidence locally)

ATSD & IDSA 2004 Recommendations

Resume rekomendasi monoterapi atau kombinasi antibiotik untuk pneumoniaAnn Intensive Care. 2011; 1: 48.

Kuman ESBL banyak terdapat di ruang ICU termasuk NICU, bagian bedah dan bagian ortopedi.IJIB 2008; 2 (2): 122-8.

MeropenemAntibiotik golongan carbapenemAktif terhadap kuman penghasil ESBL (Klebsiella pneumonia, Escherichia coli, Enterobacteriaceae)Secara in vitro Meropenem mempunyai aktivitas terhadap mikroba penghasil ESBL yang lebih tinggi dibandingkan Imipenem (MIC Meropenem: 0,03-0,12 g/mL vs Imipenem: 0,06-0,5 g/mL). Stabil terhadap DeHidroPeptidase-1 di ginjal (tidak perlu dikombinasi dengan cilastatin seperti imipenem)

http://www.medscape.com/viewarticle/409761_5

KEPEKAAN MEROPENEMTrends in antimicrobial susceptibility of gram negative isolates from a paediatrics intensive care unit in Warsaw: results from the MYSTIC proggramme(1997-2007). JAC 2008: 1-7.

MEKANISME KERJAMenghambat sintesis dinding sel bakteri

Bakterisidal (kematian bakteri)

Indikasi MeropenemPneumonia, termasuk pneumonia nosokomialInfeksi kulit dan struktur kulitInfeksi saluran kemihSeptikemia Infeksi intra-abdominalMeningitisMEROFEN/Product Profile, PT Kalbe FarmaInfeksi ginekologi

DOSISBolus lambat (5 menit), infus (15 - 30 menit)

MEROFEN/Product Profile, PT Kalbe Farma

Usia Jenis InfeksiDosisDEWASAPneumonia, ISK, infeksi ginekologi, infeksi kulit dan struktur kulit500 mg IV tiap 8 jamPneumonia nosokomial, peritonitis, infeksi pd pasien neutropenia, septikemia 1 g IV tiap 8 jamMeningitis2 g IV tiap 8 jamBAYI > 3 bulan ANAK 12 tahun

ANAK > 50 kg10 20 mg/kgBB tiap 8 jam

40 mg/kgBB tiap 8 jam (meningitis), maksimum 2 g tiap 8 jam= dewasa

PENYESUAIAN DOSISPasien gangguan fungsi hati TIDAK perlu penyesuaian dosisMEROFEN/Product Profile, PT Kalbe Farma

Klirens Kreatinin (mL/menit)Dosis (dosis rekomendasi : 500 mg -2 g)Frekuensi26 - 50Dosis rekomendasiTiap 12 jam10 - 25 dosis rekomendasiTiap 12 jam< 10 dosis rekomendasiTiap 24 jam

EFEK SAMPINGNorbi S, et. al. Scan.J of Infect Dis. 1999:31:3-10

KLASIFIKASI QUINOLONES DAN CAKUPAN AKTIVITAS ANTIBAKTERIAm Fam Physician 2000; 61: 2741-8

Generasi 1Generasi 2Generasi 3Generasi 4Nalidixic acid,Oxolinic acid,CinoxacinLomefloxacin,NorfloxacinOfloxacin,CiprofloxacinLevofloxacin,GrepafloxacinTrovafloxacin,MoxifloxacinAktivitas mikrobiologiEnterobacteriaceaeEnterobacteriaceae + P. aeroginosaEnterobacteriaceae+AtipikalP. aeruginosaEnterobacteriaceaeP. aeruginosa (+/-)Atipikal+StreptococciEnterobacteriaceaceP.aeruginosa (+/-)AtipikalStreptococci+anaerobTempat infeksiHanya saluran kemihHanya saluran kemihSistemik + sal.kemihSistemik sal. kemihSistemik sal. kemih

FARMAKODINAMIKLEVOFLOXACINEnzim DNA gyrase dan topoisomerase IV dari bakteriBakteri matiXPI Cravit. 2001

MIC90 Levofloxacin terhadap Bakteri Penyebab InfeksiDrugs 2008; 68(4): 535-65, Thauvin-Eliopoulos C, Eliopoulos GM. Quinolone antimicrobial agent. 3rd ed. 2003

BakteriMIC90 (mg/L)Streptococcus pneumoniaePenicillin susceptiblePenicillin intermediatePenicillin resistant0,5 - 16111Escherichia coli 0,06 - > 8Haemophilus influenzae0,008 - 0,06Haemophilus parainfluenzae 0,06Klebsiella pneumoniae0,5 - > 8Moraxella catarrhalis0,03 0,06Proteus mirabilis 0,05 2Pseudomonas aeruginosa0,5 - 64Salmonella spp0,03-0,25

METABOLISME DAN EKSKRESI LEVOFLOXACINMetabolisme: terbatas Ekskresi: melalui ginjal terutama dalam bentuk utuh (87 % dalam 48 jam)melalui feses (< 4 % dalam 72 jam)PI Cravit. 2001

DOSIS UMUMwww.rxlist.comTyphoid fever500 mg7

Penyesuaian Dosis pada Gangguan Fungsi Ginjal Dosis 500 mgPDR 2007,*http://www.drugs.com/pro/levaquin.html#section-16.7*Acute Exacerbation Chronic Bronchitis**Skin and Skin Structure Infecton

Tipe InfeksiKlirens Kreatinin (mL/menit)Dosis Awal Dosis PemeliharaanCommunity Acquired InfectionAcute Exacerbation of Chronic BronchitisSinusitisSkin and Skin Structure InfectionsProstatitis50-80Tidak perlu penyesuaian dosis20-49500 mg250 mg q 24 jam10-19

500 mg

250 mg q 48 jam

HemodialisisCAPD

Penyesuaian Dosis pada Gangguan Fungsi GinjalDosis 750 mgPDR 2007,*http://www.drugs.com/pro/levaquin.html#section-16.7

Tipe InfeksiKlirens kreatinin (mL/menit)Dosis awal(mg)Dosis berikutnyaHospital Acquired PneumoniaCommunity Acquired PneumoniaSinusitis bakterial akutInfeksi kulit dan struktur kulit dengan komplikasiInfeksi saluran kemih dengan komplikasi dan pielonefritis akut50-80Tidak ada penyesuaian dosis20-49750750 tiap 48 jam10-19

750

500 tiap 48 jam

HDCAPD

PERBANDINGAN EFEK SAMPING PADA ANTIBIOTIKA QUINOLONE

INTERAKSI OBATAntasida, sukralfat, kation logam, multivitaminDapat menyebabkan penurunan absorpsi pada saluran cerna dari levofloxacin.Obat antiinflamasi non steroid (AINS)Dapat meningkatkan risiko stimulasi susunan saraf pusat dan kejang.Obat antidiabetesPengawasan kadar glukosa direkomendasikan ketika levofloxacin digunakan bersamaan dengan obat antidiabetes dimana pernah dilaporkan terjadi gangguan kadar glukosa darah (hipoglikemia atau hiperglikemia) pada penggunaan fluoroquinolone lain.

KESIMPULAN Meropenem & Levofloxacin LevofloxacinQuinolone generasi ketiga dengan spektrum anti-bakteri luasDosis praktis 1x/hrKombinasi Meropenem dan Lfx direkomendasikan untuk infeksi berat (seperti sepsis atau pneumonia nosokomial) yang disebabkan bakteri MDR seperti Pseudomonas, Acinetobacter sp, atau Klebsiella Pneumoniae.

MeropenemMeropenem adalah gol carbapenem yang stabil terhadap enzim beta-lactamase & DHP-1Mempunyai spektrum antibakteri yang luasMerofen diindikasikan untuk penanganan infeksi beratDapat digunakan baik pada dewasa maupun anak (> 3 bulan)

TERIMA KASIHSEMOGA SUKSES

Treatment guidelines for the management of CAP have been endorsed by various organisations. The most representative are the consensus guidelines of the Infectious Diseases Society of America and the American Thoracic Society (IDSA/ATS), the British Thoracic Society, and the European Respiratory Society and European Society for Clinical Microbiology and Infectious Diseases. These guidelines state that the selection of antimicrobial regimens for empirical therapy in CAP should be based on risk group stratification and the most likely causative pathogens. Other factors in the choice of antimicrobial agents in CAP are pharmacokinetics/pharmacodynamics, allergy, intolerance, previous use of antibiotics, compliance, cost, potential adverse events and knowledge of local pathogen susceptibility. Guideline recommendations are generally for a class of antibiotic rather than a specific drug. The goals of antimicrobial treatment are to reduce or eradicate the bacterial load in order to achieve clinical success, reduce associated morbidity and mortality, and minimise the potential for development of resistance.

Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44: S2772WoodheadM, Blasi F, Ewig S et al. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect 2011; 17(Suppl 6): E1E59Lim WS, Baudoin SV, George RC et al. Guidelines for the management of community acquired pneumonia in adults: update 2009. Thorax 2009: 64 (Suppl 3): iii1iii55

**Recent guidelines by the ERS recommend the following: Initial empirical treatment/treatment options for non-ICU hospitalised patientspenicillin G macrolideaminopenicillin macrolideaminopenicillin/-lactamase inhibitor macrolidenon-anti-pseudomonal 2nd or 3rd generation cephalosporin macrolidelevofloxacin, moxifloxacin*

Severe CAPNo Pseudomonas aeruginosa risk factorsnon-anti-pseudomonal 3rd generation cephalosporin + macrolidenon-anti-pseudomonal 3rd generation cephalosporin + moxifloxacin or levofloxacin

P. aeruginosa risk factors:anti-pseudomonal cephalosporin or acylureidopenicillin/-lactamase inhibitor or carbapenem (meropenem preferred) + ciprofloxacin + macrolide + aminoglycoside

*Antibiotic must be effective against Streptococcus pneumoniae within the fluoroquinolones moxifloxacin has highest anti-pneumococcal activity

WoodheadM, Blasi F, Ewig S et al. Guidelines for the management of adult lower respiratory tract infections--full version. Clin Microbiol Infect 2011; 17(Suppl 6): E1E59

*The first 48 hours of evolution of patients with CAP are critical. Non-immunocompromised adults hospitalised with CAP were prospectively observed from 1995 to 2005. Early deaths, defined as death due to any cause up to 48 hours after admission, were compared with all patients who survived for more than 48 hours. Furthermore, early deaths were compared with late deaths (patients who died >48 hours) and with survivors.

Of 2457 patients, 57 (2.3%) died within 48 hours after admission. Overall mortality was 7.7%. The main causes of early mortality were respiratory failure and septic shock/multiorgan failure. Independent factors associated with early deaths were increased age, altered mental status at presentation, multilobar pneumonia, shock at admission, pneumococcal bacteraemia and discordant empirical antibiotic therapy.

Garcia-Vidal C,Fernndez-Sab N,Carratal Jet al. Early mortality in patients with community-acquired pneumonia: causes and risk factors. Eur Respir J 2008; 32: 7339

*Early initiation of appropriate antibiotic therapy for septic shock and survival indicates that early intervention is associated with an increase in cumulative survival. The survival fraction is the fraction of patients surviving to hospital discharge after receiving effective therapy initiated within the given time interval. The cumulative effective antimicrobial fraction is the cumulative fraction of patients having received effective antimicrobials at any given time point.

Deresinski S. Principles of antibiotic therapy in severe infections: optimizing the therapeutic approach by use of laboratory and clinical data. Clin Infect Dis 2007; 45: S177S183

*A retrospective cohort study of 161 ICU patients with CAP was conducted over a 3-year period. Timing of the ICU admission was dichotomised into early ICU admission (EICUA, direct admission or within 24 hours) and late ICU admission (LICUA day 2). A multivariable analysis using Cox proportional hazard model was created with the primary outcome of 30-day mortality (dependent measure) and the American Thoracic Society (ATS) severity adjustment criteria and time to ICU admission as the independent measures.

Eighty-eight percent (n=142) were EICUA patients compared with 12% (n=19) LICUA patients. Groups were similar with respect to age, sex, co-morbidities, clinical parameters, CAP-related process of care measures, and need for mechanical ventilation. LICUA patients had lower rates of ATS severity criteria at presentation (26.3% vs 53.5%; P=0.03). LICUA patients (47.4%) had a higher 30-day mortality compared with EICUA (23.2%) patients (P=0.02), which remained after adjustment in the multivariable analysis (hazard ratio 2.6; 95% CI 1.25.5; P=0.02).

Patients with severe CAP with a late ICU admission have increased 30-day mortality after adjustment for illness severity.

Restrepo MI,Mortensen EM,Rello J et al. Late admission to the ICU in patients with community-acquired pneumonia is associated with higher mortality. Chest 2010; 137: 5527

*For patients requiring treatment within an intensive care unit (ICU) a -lactam (cefotaxime, ceftriaxone, or ampicillinsulbactam) plus either azithromycin or a fluoroquinolone.

For Pseudomonas infection, it is recommended to use an anti-pneumococcal, anti-pseudomonal -lactam (piperacillintazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin (750 mg dose) OrAnti-pseudomonal -lactam (piperacillintazobactam, cefepime, imipenem, or meropenem) plus an aminoglycoside and azithromycinOrAnti-pseudomonal -lactam (piperacillintazobactam, cefepime, imipenem, or meropenem) plus an aminoglycoside and an anti-pneumococcal fluoroquinolone.

For community-acquired methicillin-resistant Staphylococcus aureus infection, add vancomycin or linezolid. Infections caused by the majority of CAP pathogens will be adequately treated by the recommended empirical regimens. The emergence of methicillin-resistant Staph. aureus as a CAP pathogen and the small but significant incidence of CAP due to Pseudomonasaeruginosa are the exceptions. These pathogens occur in specific epidemiological patterns and/or with certain clinical presentations, for which empirical antibiotic coverage may be warranted. However, diagnostic tests are likely to be of high yield for these pathogens, allowing early discontinuation of empirical treatment if results are negative.

Mandell LA, Wunderink RG, Anzueto A et al. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis 2007; 44: S2772

*****Kuman ESBL ini ternyata cukup banyak ada di ruang ICU seperti yang terlihat di tabel (yang diberi tanda).Namun memang RS yang berbeda akan memiliki pola kuman tersendiri.**Kepekaan meropenem terhadap isolat di ICU sangat baik yaitu di atas 90%.**Mekanisme kerja meropenem: (baca)Meropenem mempunyai sifat bakterisidal sehingga cocok digunakan untuk pasien yang mempunyai pertahanan tubuh yang rendah seperti misalnya pasien di ICU.

Keterangan: bakterisidal adalah suatu efek dari antibiotika tertentu yang dapat membunuh bakteri.Istilah lain bakteriostatik adalah suatu efek dari antibiotika tertentu yang hanya menghambat pertumbuhan bakteri (tidak membunuh bakteri)

Jelas*Tabel ini menunjukkan dosis penggunaan meropenem dimana indikasi yang berbeda memiliki dosis yang berbeda pula.

Seperti biasa, dosis anak dan dewasa berbeda dimana dapat digunakan untuk anak umur > 3 bulan sedangkan pada anak < 3 bulan, keamanan dan efektivitasnya masih belum diketahui.

Anak dengan berat badan > 50 kg menggunakan dosis yang sama dengan dewasa. **Diperlukan penyesuaian dosis pada pasien dengan gangguan fungsi ginjal yaitu klirens kreatinin