BUKU PEGANGAN TUTOR

Modul NYERI SAAT BERKEMIH

Diberikan pada mahasiswasemester IV FK UNHAS

SISTEM UROGENITALIAFAKULTAS KEDOKTERAN

UNIVERSITAS HASANUDDINMAKASSAR

2006

PENDAHULUAN

Modul nyeri saat berkemih ini diberikan pada mahasiswa yang mengambil mata

kuliah sistim Urogenitalia di semester IV. TIU dan TIK pada sistim ini disajikan pada

permulaan buku modul agar dapat dimengerti secara menyeluruh tentang konsep dasar

penyakit-penyakit Sistem Urogenitalia yang memberikan gejala nyeri saat berkemih.

Mahasiswa diharapkan mampu menjelaskan semua aspek tentang system Urogenitalia

dan patomekanisme terjadinya penyakit, kelainan jaringan, dan pemeriksaan lain yang

dibutuhkan pada penyakit yang memberikan gejala nyeri saat berkamih..

Sebelum menggunakan modul ini, mahasiswa diharapkan membaca TIU dan TIK

sehingga tidak terjadi penyimpangan pada diskusi dan tujuan serta dapat dicapai

kompetensi minimal yang diharapkan. Bahan untuk diskusi dapat diperoleh dari bacaan

yang tercatum di akhir modul. Kuliah pakar akan diberikan atas permintaan mahasiswa

yang berkaitan dengan penyakit ataupun penjelasan dalam pertemuan konsultasi antara

peserta kelompok diskusi mahasiswa dengan tutor atau ahli yang bersangkutan.

Penyusun mengharapkan modul ini dapat membantu mahasiwa dalam

memecahkan masalah penyakit Urogenitalia yang disajikan.

Makassar, 2 Desember 2005

Penyusun

TUJUAN INSTRUKSIONAL UMUM

Setelah mempelajari modul ini mahasiswa diharapkan dapat menjelaskan tentang penyakit-penyakit yang menyebabkan gejala nyeri saat berkamih, penyebab dan patomekanisme, gambaran klinik, cara diagnosis, penanganan dan pencegahan penyakit-penyakit yang menyebabkan nyeri saat berkamih.

TUJUAN INSTRUKSIONAL KHUSUS Setelah pembelajaran dengan modul ini mahasiswa diharapkan dapat:

A. Menyebut penyakit-penyakit yang menyebabkan gejala nyeri saat berkamih.

B. Menjelaskan tentang patomekanisme terjadinya penyakit-penyakit yang

menyebabkan gejala nyeri saat berkamih

1. menguraikan struktur anatomi, histologi dan histofisologi dari sistim uropoetika

2. menyebutkan fungsi masing-masing bagian dari

nefron, fungsi sel-sel JGA dalam renin angiotensin system,

3. menjelaskan faktor-faktor yang mempengaruhi

GFR, prinsip hukum Starling pada filtrasi ginjal, dan dapat menghitung GFR,

4. menjelaskan mekanisme dan proses reabsorbsi dan

sekresi di tubulus, mengapa ada zat yang mempunyai Tmax, peranan hormon

aldosteron dan ADH pada reabsorbsi, pengaturan reabsorbsi dan sekresi di

tubulus, counter current mechanism, proses reabsorbsi dan sekresi pada keadaan

tertentu seperti dehidrasi dan overhidrasi

5. menjelaskan biokimia urine dan kompensasi ginjal dalam keseimbangan asam

basa

6. menjelaskan tentang penyebab penyakit-penyakit yang menyebabkan gejala nyeri

saat berkamih

7. menjelaskan hubungan antara penyebab, respon dan perubahan jaringan pada

patogenesis terjadinya penyakit yang menyebabkan gejala nyeri saat berkamih

C. menjelaskan tentang gejala-gejala klinik penyakit-penyakit: GNA, BSK, Nefropathy,

dan penyakit non-uropoetik msialnya alergi dan kelainan ginjal akibat rehidrasi.

D. menjelaskan tentang cara-cara diagnosis GNA, BSK, Nefropathy, dan penyakit non-

uropoetik msialnya alergi dan kelainan ginjal akibat rehidrasi.

menjelaskan tentang cara anamnesis terarah pada penderita penyakit-penyakit di

atas

1. menjelaskan tentang cara pemeriksaan fisik penderita penyakit-penyakit di atas ,

menggambarkan perubahan histopatologi penyakit-penyakit di atas

menjelaskan fase pre-analitik, analitik & Post analitik dari prosedur tes/Lab pada

penyakit-penyakit di atas

menganalisa hasil laboratorium pada penderita penyakit-penyakit di atas .

menjelaskan gambaran Rontgen dari saluran kemih yang normal, dan pada

penyakit di atas.

E. menjelaskan tentang penatalaksanaan pada penderita penyakit-penyakit di atas

menyebutkan obat-obatan yang dipakai pada penderita dengan gejala nyeri saat

berkamih,

menjelaskan farmakodinamik dan farmakokinetik obat-obat yang digunakan

dalam terapi penyakit yang menyebabkan gejala nyeri saat berkamih

menjelaskan asuhan nitrizi pada penyakit-penyakit yang menyebabkan gejala

nyeri saat berkamih

F. Menjelaskan tentang aspek epidemiologi penyakit-penyakit yang tersebut di atas

PROBLEM TREE

Lab : Urine Kimia darah UrinalisisPemeriksaan lain :BNOCT Scan, USG

Diagnosis Banding BSKNefropathyTumor UG

Anamnesis :Disuria, pollakisuriaDemam +/-, ada darah diakhir miksi

Fisik Diagnostik :Suhu tubuh subfebrilTampak nyeri

NYERI SAAT BERKEMIH

AnatomiHistologiFisiologiBiokimiaPatologi Anatomi FarmakologiMikrobiologi

Bedah

Medikamentosa Non MedikamentosaNutrisi

PenatalaksanaanPengendalian

Preventif Promotif Non Bedah

Skenario 1. Nyeri saat berkemih

1. Setelah membaca dengan teliti skenario di atas anda harus mendiskusikan kasus

tersebut pada satu kelompok diskusi terdiri dari 12 – 15 orang, dipimpin oleh seorang

ketua dan seorang penulis yang dipilih oleh anda sendiri. Ketua dan sekretaris ini

sebaiknya berganti-ganti pada setiap kali diskusi. Diskusi kelompok ini bisa dipimpin

oleh seorang tutor atau dilakukan secara mandiri oleh kelompok.

2. Melakukan aktivitas pembelajaran individual di perpustakaan dengan menggunakan

buku ajar, majalah, slide, tape atau video, dan internet, untuk mencari informasi

tambahan.

3. Melakukan diskusi kelompok mandiri (tanpa tutor) , melakukan curah pendapat bebas

antar anggota kelompok untuk menganalisa dan atau mensintese informasi dalam

menyelesaikan masalah.

4. Berkonsultasi pada nara sumber yang ahli pada permasalahan dimaksud untuk

memperoleh pengertian yang lebih mendalam (tanpa pakar).

5. Mengikut kuliah khusus (kuliah pakar) dalam kelas untuk masalah yang belum jelas

atau tidak ditemukan jawabannya.

6. Melakukan latihan dilaboratorium keterampilan klinik dan praktikum di laboratorium.

Seorang wanita, 25 thn datang ke RS dengan keluhan nyeri saat berkemih dan frekeunsi berkemih yang meningkat. Keluhan ini telah dirasakan 3 hari belakangan ini. Pada akhir kencing, urine bercampur darah

TUGAS MAHASISWA

PROSES PEMECAHAN MASALAH

Dalam diskusi kelompok dengan menggunakan metode curah pendapat, mahasiswa

diharapkan memecahkan problem yang terdapat dalam skenario ini, yaitu dengan

mengikuti 7 langkah penyelesaian masalah di bawah ini:

1. Klarifikasi istilah yang tidak jelas dalam scenario di atas, dan tentukan kata/ kalimat

kunci skenario diatas.

2. Identifikasi problem dasar scenario diatas dengan, dengan membuat beberapa

pertanyaan penting.

3. Analisa problem-problem tersebut dengan menjawab pertanyaan-pertanyaan diatas.

4. Klasifikasikan jawaban atas pertanyaan-pertanyaan tersebut di atas.

5. Tentukan tujuan pembelajaran yang ingindi capai oleh mahasiswa atas kasus

tersebut diatas.

6. Cari informasi tambahan tentang kasus diatas dari luar kelompok tatap muka.

Langkah 6 dilakukan dengan belajar mandiri.

7. Laporkan hasil diskusi dan sistesis informasi-informasi yang baru ditemukan.

Langkah 7 dilakukan dalm kelompok diskusi dengan tutor.

Penjelasan :

Bila dari hasil evaluasi laporan kelompok ternyata masih ada informasi yang

diperlukan untuk sampai pada kesimpulan akhir, maka proses 6 bisa diulangi, dan

selanjutnya dilakukan lagi langkah 7.

Kedua langkah diatas bisa diulang-ulang di luar tutorial, dan setelah informasi

dirasa cukup maka pelaporan dilakukan dalam diskusi akhir, yang biasanya dilakukan

dalam bentuk diskusi panel dimana semua pakar duduk bersama untuk memberikan

penjelasan atas hal-hal yang belum jelas.

1. Pertemuan pertama dalam kelas besar dengan tatap muka satu arah dan tanya jawab.

Tujuan : menjelaskan tentang modul dan cara menyelesaikan modul, dan membagi

kelompok diskusi. Pada pertemuan pertama buku modul dibagikan.

2. Pertemuan kedua : diskusi mandiri. Tujuan :

* Memilih ketua dan sekretaris kelompok,

* Brain-storming untuk proses 1 – 3,

* Membagi tugas

3. Pertemuan ketiga: diskusi tutorial dipimpin oleh mahasiswa yang terpilih menjadi

ketua dan penulis kelompok, serta difasilitasi oleh tutor. Tujuan: untuk melaporkan

hasil diskusi mandiri dan menyelesaikan proses sampai langkah 5.

4. Anda belajar mandiri baik sendiri-sendiri. Tujuan: untuk mencari informasi baru yang

diperlukan,

5. Pertemuan keempat: adalah diskusi tutorial. Tujuan: untuk melaporkan hasil diskusi

lalu dan mensintese informasi yang baru ditemukan. Bila masih diperlukan informasi

baru dilanjutkan lagi seperti No. 2 dan 3.

6. Pertemuan terakhir: dilakukan dalam kelas besar dengan bentuk diskusi panel untuk

melaporkan hasil diskusi masing-masing kelompok dan menanyakan hal-hal yang

belum terjawab pada ahlinya (temu pakar).

TIME TABLE

PERTEMUANI II III IV V VI VII

Pertemuan I(Penjelasan)

Pertemuan Mandiri(Brain

Stroming)

Tutorial I Pengum-

pulan informasiAnalisa &

sintese

Mandiri

PraktikumCSL

Kuliah kosultasi

Tutorial II(Laporan &

Diskusi)

Pertemuan Terakhir (Laporan)

JADWAL KEGIATAN

STRATEGI PEMBELAJARAN

1. Diskusi kelompok difasilitasi oleh tutor

2. Diskusi kelompok tanpa tutor

3. CSL : Pemeriksaan benjolan pada leher

4. Praktikum PA

5. Konsultasi pada pakar

6. Kuliah khusus dalam kelas

7. Aktivitas pembelajaran individual diperpustakaan dengan menggunakan buku ajar

Majalah,slide,tape atau video dan internet

A. Buku Ajar dan Jurnal

1 Urology : R.W. Barnes, R.T.Bergman, H.Hodley, Toppan Co.(S) PTE-LTD,Singapore2 Davitson VL and Sittman DB : Biochemistry3 Kumar, Contran, Robbins: Pathology Basis of Diseases, 20034 Chandrasoma- Taylor: Concise Pathology, 19995 Kenneth J Rothman, 1986, Modern Epidemiology, Little Brownc and Company, Bon 6 World Health Organization, 1992, International statistical Classification of Diseases

an and related Health Problems, 10th revision, volume 1, WHO, Geneva

7 Goodharmt R : Modern nutrition in health and disease, Lee Ferbeger, 20028 Robinson : Normal and Therapeutic Nutrition, Mac Millian Co., New York9 Lenne EH et al ; Manual of Clinical Microbiology , 4th edition, 1985

10 Prescott LM et al : Microbiology, 2nd edition, Wm.c Brown Publisher, Melbourne, 1993

11 WF. Ganong : Review of Medical Physiology, edisi 20, 200312 Synopsis of analysis of Roentgen sign in general Radiology, Isadore Meschan, 197613 Junguiera LC, Carneiro J : Basic Histology 3th edition, Los Altos California USA,

Lange Medical Publication, 198014 Stites DP, Stobo JD, Fudenberg HH : basic and Clinical Immunology, 4th edition, Los

Altos California, Lange Medical Publication, 1982

15 Schlesinger ER, Sultz HA, Mosher WE, et al. The Nephrotic Syndrome. Its incidence and implications for the community. Am J Dis Child 1968, 116; 623

16 International Study of Kidney Disease in Children. Nephrotic Syndrom in Children. Prediction of histopathology from clinical and laboratory characteristics at time of diagnosis. Kidney Int. 1978, 13: 159.

17 Kher KK. Obstructive uropathy. Dalam : Kher KK, Marker SP, penyunting. Clinical Pediatric Nephrology. New York: Mc Graw – Hill 1992: 447-65.

18 Behrman RE. Nelson textbook of pediatrics; edisi ke 14. Philadelphia: WB Saunders,

BAHAN BACAAN & SUMBER INFORMASI LAIN

1992; 1344-50.19 Homes HD, Weinberg JM. Toxic nephropathies. Dalam: Brenner Rector FC,

penyunting, The Kidney, II; edisi ke-Philadelphia: WB Saunders Co, 1986; 1491-532.20 Barrat TM. Acute renal failure. Dalam: Holliday MA, Barrat TM, Vernier RL,

penyunting. Pediatric nephrology, edisi ke-2. Baltimore: Williams & Wilkins 1987; 766-72.

21 Kher KK. Chronic renal failure. Dalam Kher KK, Marker SP, penyunting, clinical pediatric nephrology. New York: MC Graw-Hill Inc, 1992, 501-41.

22 Karjomanggolo WT, Alatas H. Kelainan congenital ginjal dan saluran kemih. Dalam: Naskah lengkap PKB. IKA XXVI : Penelitian tractor urinarius pada anak. Jakarta 11 – 12 September 1992: 1176-84.

23 Londe S causes of hypertension in the young. Pediatric Clin North Am 1978; 25-55.24 Henry JB : Clinical Diagnosis and Manage,ent by laboratory Methods, 19th ed, 199625 H. Beers and R. Berkow editor : The Merck Manual 17th ed, 199926 Harrison : Disorders of the kidney and Urinary tractus, 15th edition, Volume I, Mc

Graw Hill, 2002, pp : 1535-163027 Ginjal Hipertensi dalam Buku Ajar Ilmu Penyakit Dalam jilid II, edisi III, Balai Penerbit

FKUI Jakarta, 2001

B. Diktat dan hand-out

1. Diktat Anatomi2. Diktat Histologi3. Buku Ajar Fisiologi Ginjal4. Diktat Kuliah Radiologi

C. Sumber lain : VCD, Film, Internet, Slide, Tape

D. Nara sumber (Dosen Pengampu)

DAFTAR NAMA NARA SUMBER

No. NAMA DOSEN BAGIAN TLP. KANTOR

HP/FLEXI

1. Prof.Dr. dr. Syarifuddin Rauf Sp.PA

Anak 0811411109

2. Prof.Dr.dr. Syakib Bakri, Sp.PD

Penyakit Dalam 0816250620

3. Prof.dr. Ahmad M Palinrungi Sp.B, Sp.U

Bedah Urologi 08164384040

4. Prof.Dr.dr. M.Dali Amiruddin, Sp.KK

Kulit Kelamin 08194229858

5. Dr. Irfan Idris, MS Fisiologi 584730 0813426953486. Dr. Theopilus Buranda, MS Anatomi 0813424364447. Dr. Robby Lianury Histologi 08114117238. Dr. Agnes Kwenang, MS Biokimia9. Dr. dr. Gatot Lawrence Patologi 0816255306

Anatomi10. Dr. dr. Nurpudji Astuti,

SpGKGizi 0811443856

11. Dr. dr. Fatmawati Farmakologi 08152412036812. Dr. Randana Bandaso, MS Patologi

Anatomi13. Dr. Nurlaily Idris, Sp.R Radiologi 081144106414. Dr. H, Ibrahim Samad, SpPK Patologi Klinik15. Dr. Baedah Madjid, SpMK Mikrobiologi 081144432616. Dr. Sastri, SpKK Kulit Kelamin 08124217393

Apa yang dimaksud dan mekanisme ‘kata kunci’ berikut ini :

o Nyeri saat berkemih (dysuria) : Rasa nyeri saat mulai dan selama

berkemih

o Frekuensi berkemih meningkat (Pollakisuria) : Frekuensi berkemih

meningkat dibanding biasanya

o Darah pada akhir kencing : tampak ada darah (gross hematuria) pada akhir

kencing

o Dirasakan 3 hari yang lalu : dirasakan baru 3 hari yang merupakan proses

akut

o Wanita : resiko ISK pada wanita > pria

o Usia 25 tahun : usia puncak 18-30 tahun untuk ISK dimana merupakan

usia perkawinan dan kehamilan.

Apa penyebab dan bagaimana pato-mekanisme gejala-gejala yang menjadi kata

kunci tersebut

1. Dysuria : dihubungkan dengan inflamasi pada vesica urinaria

1. Pollakisuria : dihubungkan dengan inflamasi pada vesica urinaria

2. Hematuria : dihubungkan dengan inflamasi pada vesica urinaria

Sebutkan beberapa penyakit yang dapat di differential diagnosis

dengan tanda dan gejala pada skenario

Bladder Stones Bladder Trauma Cystitis, Nonbacterial Gastroenteritis, Bacterial Glomerulonephritis, Acute Gonococcal Infections Herpes Simplex Interstitial Cystitis Nephrolithiasis Pancreatitis, Acute Pyelonephritis, Acute Trichomoniasis

PETUNJUK UNTUK TUTOR

Urethritis Vaginitis

Pemeriksaan penunjang yang dibutuhkan untuk menegakkan diagnosis penyakit

yang termasuk dalam DD penyakit tersebut

o Urinalysis

o Kultur urine

o Radiologi : USG, CT Scan

Bagaimana cara penatalaksanaan dari penyakit-penyakit yang termasuk dalam

DD penyakit tersebut

1. Medikamentosa

2. Bedah / ESWL: bila disertai batu

3. Diet

Epidemiologi dan cara pencegahan penyakit tersebut

1. Prevalensi lebih banyak pada wanita dibanding pria, di USA 25-40% pada

wanita uisa 20-40 thn

2. Mortalitas pada wanita dengan ISK 37% sedang wanita tanpa ISK 28%

(kohort data dari Swedia)

3. 25% mengalami rekurrent, sehingga pemberian regiment antibiotik perlu

diperhatikan, mengganti kontrasepsi, pada menopouse dengan pemberian

HRT,

Komplikasi penyakit-penyakit yang termasuk DD pada skenario

1. Bakterimia

2. Sepsis

3. Shock

4. Kematian

Prognosis penyakit-penyakit tersebut

1. Prognosis baik, tetapi angka rekurrent mencapai 25%2. Bila terjadi Pyelonefritis prognosis memburuk

Urinary Tract Infection, Females

Background: UTIs may be referred to as cystitis or pyelonephritis, terms that refer to the lower and upper urinary tract, respectively. The terms bacteriuria and candiduria describe bacteria or yeast in the urine. Very ill patients may be referred to as having urosepsis.

The following terms are defined for uniformity in this article:

Asymptomatic bacteriuria (ASB) refers to 2 consecutive urine cultures growing more than 100,000 colony-forming units (CFU) of a bacterial species in a patient lacking symptoms of a UTI.

Uropathogens are specific bacteria that have been clinically associated with invasion of the urinary tract.

Complicated UTIs are defined as UTIs that are associated with metabolic disorders, that occur at sites other than the urinary bladder, or that are secondary to anatomic or functional abnormalities that impair urinary tract drainage. Most complicated UTIs are nosocomial in origin. The most common pathogens include Escherichia coli, enterococci, Pseudomonas aeruginosa, candidal species, and Klebsiella pneumoniae. Complicated UTIs may be subdivided into the following 4 categories:

1. Structural abnormalities - Calculi, infected cysts, renal/bladder abscesses, certain forms of pyelonephritis, spinal cord injury (SCI), catheters

2. Metabolic/hormonal abnormalities - Diabetes, pregnancy 3. Impaired host responses - Transplant recipients, patients with AIDS 4. Unusual pathogens - Yeast, etc

Pathophysiology: In general, 3 main mechanisms are responsible for UTIs, including (1) colonization with ascending spread, (2) hematogenous spread, and (3) periurogenital spread of infection. Specific organism characteristics, defects in host defenses, and pathophysiologic details concerning particular UTIs now will be discussed.

Bacterial virulence

Uropathogenic bacteria, derived from a subset of fecal flora, have traits that enable adherence, growth, and resistance of host defenses, resulting in colonization and infection of the urinary tract.

Adhesins are bacterial surface structures that enable attachment to host membranes. In E coli infection, these include both pili (ie, fimbriae) and outer membrane proteins (eg, Dr hemagglutinin). P fimbriae, which attach to globoseries-type glycolipids found in the colon and urinary epithelium, are associated with pyelonephritis, cystitis, and also are found in many E coli strains causing urosepsis. Type 1 fimbriae bind to mannose-containing structures found in many different cell types, including the major protein found in human urine, Tamm-Horsfall protein. Whether this facilitates or inhibits uroepithelial colonization is the subject of some debate.

Other factors that may be important for E coli virulence in the urinary tract include capsular polysaccharides, hemolysins, cytotoxic necrotizing factor (CNF) protein, and aerobactins. Several Kauffman serogroups of E coli may be more likely to cause UTIs, including O1, O2, O4, O6, O16, and O18. Another example of bacterial virulence is the swarming capability of Proteus mirabilis. Swarming involves the expression of specific genes when these bacteria are exposed to surfaces such as catheters. This results in the coordinated movement of large numbers of bacteria,

enabling P mirabilis to move across solid surfaces. This likely explains the association of P mirabilis UTIs with instrumentation of the urinary tract.

Host resistance

Most uropathogens gain access to the urinary tract via an ascending route. The shorter length of the female urethra allows uropathogens easier access to the bladder. The continuous unidirectional flow of urine helps to minimize UTIs, and anything that interferes with this increases the host's susceptibility to UTI. Examples of interference include volume depletion, sexual intercourse, urinary tract obstruction, instrumentation, use of catheters not drained to gravity, and vesicoureteral reflux.

Secretory defenses help to promote bacterial clearance and prevent adherence. Secretory immunoglobulin A (IgA) reduces attachment and invasion of bacteria in the urinary tract. Women who are nonsecretors of the ABH blood antigens appear to be at higher risk of recurrent UTIs; this may occur because of a lack of specific glycosyltransferases that modify epithelial surface glycolipids, allowing E coli to bind to them better.

Urine itself has several antibacterial features that suppress UTIs. Specifically, the pH, urea concentration, osmolarity, and various organic acids prevent most bacteria from surviving in the urinary tract.

Pathophysiologic details of complicated urinary tract infections

Pyelonephritis almost always is the result of bacteria migrating from the bladder to the renal parenchyma, which is enhanced by vesicourethral reflux. In uncomplicated pyelonephritis, the bacterial invasion and renal damage are limited to the pyelocalyceal-medullary region; in complicated pyelonephritis, all regions of the kidney may be affected. If the infection progresses, bacteria may invade the bloodstream, resulting in bacteremia.

Complicated pyelonephritis results from structural and functional abnormalities, urologic manipulations, or underlying disease. Complicated pyelonephritis includes pyelonephritis in men and pyelonephritis elderly people. Patients with diabetes may develop emphysematous or xanthogranulomatous pyelonephritis and necrotizing papillitis.

Subclinical pyelonephritis should be considered in indigent people; pregnant women; people with diabetes; people with alcoholism; and patients with a history of pyelonephritis, renal transplant, UTI before age 12 years, and more than 3 UTIs in the past year.

Calculi related to UTIs most commonly occur in women with recurrent UTIs from Proteus, Pseudomonas, and Providencia species (see Image 1); bacterial biofilms serve to assist struvite growth. Because magnesium ammonium phosphate is acid soluble, stone formation does not tend to occur with a urinary pH lower than 7.19. Increases in ammonia raise the pH and injure the uroepithelial glycosaminoglycan layer, contributing to bacterial adherence. Alkalinity also increases the amount of phosphate and carbonate available to bind calcium and magnesium.

Renal corticomedullary abscesses usually are associated with vesicoureteral reflux or urinary tract obstruction, and the usual organisms include E coli, Klebsiella species, and Proteus species. Clinical syndromes include acute focal bacterial nephritis, acute multifocal bacterial nephritis, emphysematous pyelonephritis, and xanthogranulomatous pyelonephritis.

Acute focal bacterial nephritis is also known as acute lobar nephronia or focal pyelonephritis. This is an acute bacterial interstitial nephritis affecting a single renal lobe. Acute multifocal bacterial

nephritis affects more than 1 lobe (see Image 2). Emphysematous pyelonephritis is a severe, necrotizing form of acute multifocal bacterial nephritis. Retroperitoneal (ie, extraluminal) gas may be observed in the renal parenchyma and perirenal space on radiographs. This is observed most commonly in people with diabetes, but it also may be observed in patients with immunocompromise or obstruction.

Xanthogranulomatous pyelonephritis is a severe chronic infection of the renal parenchyma. The kidney is enlarged and is fixed to the retroperitoneum by either perirenal fibrosis or an extension of the granulomatous process. The inciting event appears to be renal obstruction and chronic UTI. Predisposing factors include renal calculi, lymphatic obstruction, renal ischemia, dyslipidemia, diabetes, and primary hyperparathyroidism.

A perinephric abscess is defined as a collection of purulent material between the renal capsule and Gerota fascia. A perinephric abscess may develop secondary to an intrarenal abscess, a renal cortical abscess, xanthogranulomatous pyelonephritis, chronic or recurrent pyelonephritis, or from hematogenous dissemination. Predisposing factors are similar to those for intrarenal abscess. Approximately 25% of patients have diabetes.

Over time, patients with diabetes may develop cystopathy, nephropathy, and renal papillary necrosis, complications that predispose them to UTIs. Long-term effects of diabetic cystopathy include vesicourethral reflux and recurrent UTIs; as many as 30% of women with diabetes have some degree of cystocele, cystourethrocele, or rectocele.

Vaginal candidiasis and vascular disease also play a role in recurrent infections. Hyperglycemia causes neutrophil dysfunction by increasing intracellular calcium levels, interfering with actin and, thus, diapedesis and phagocytosis.

Renal cortical abscesses (ie, renal carbuncles) usually result from hematogenous spread of bacteria. Primary sources of infection include skin infections, osteomyelitis, and endovascular infections. These are observed commonly in users of injection drug, people with diabetes, and patients on dialysis. The most common organism isolated is Staphylococcus aureus. Ten percent of cortical abscesses may rupture through the renal capsule and form a perinephric abscess.

Autosomal dominant polycystic kidney disease can lead to end-stage renal disease. Cysts may become infected from either bacteremia or from bacteriuria.

Several factors increase the risk of UTI in pregnancy. These factors include relative obstruction of the ureters (secondary to the enlarging uterus), smooth muscle relaxation of the ureter and bladder (secondary to progesterone), and aminoaciduria and glycosuria, which provide a favorable environment for bacteria to grow. E coli is the most common organism isolated from cultures, although P mirabilis and K pneumoniae also are observed. Less common agents include group B streptococci and Staphylococcus saprophyticus. Group B streptococci are isolated in approximately 5% of infections and have been linked to preterm labor; these patients should receive prophylactic antibiotics during delivery to reduce the risk of neonatal sepsis.

Risk factors for candiduria include diabetes mellitus, indwelling urinary catheters, and antibiotic use. Candiduria may clear spontaneously or may result in (or from) deep fungal infections. The presence of Candida species in the urine usually represents colonization and not infection, and, as such, not all patients with candiduria require treatment. A lower threshold for initiating treatment exists for patients with diabetes, history of renal transplantation, or genitourinary abnormalities.

Frequency:

In the US: UTIs in women are very common; approximately 25-40% of women in the United States aged 20-40 years have had a UTI. In 1998, approximately 3.2% of emergency department visits were related to symptoms involving the genitourinary tract. Estimates based on office and emergency department visits suggest per annum about 7 million episodes of acute cystitis and 250,000 episodes of acute pyelonephritis. Ten to 15% of nephrolithiasis episodes are secondary to organisms associated with stone production. The incidence of renal and perirenal abscesses is 1-10 cases per 10,000 population. Some estimate that UTIs cost at least 1 billion dollars per year.

Patients with spinal cord injuries are at an increased risk for UTIs; lower rates occur in those with incomplete injuries. In patients practicing clean intermittent catheterization, the mean incidence of UTIs is 10.3 per1000 catheter days; after 3 months, the rate is fewer than 2 per 1000 catheter days. Once a urethral catheter is in place, the daily incidence of bacteriuria is 3-10%. Because the majority will become bacteriuric by 30 days, that is a convenient dividing line between short- and long-term catheterization.

Internationally: UTIs have been well studied in Sweden and other parts of Europe, and these data are referred to frequently in this article.

Data from the tropics are less well documented. UTIs appear to be common and associated with structural abnormalities. Chronic infection from Schistosoma haematobium disrupts bladder mucosal integrity and causes urinary obstruction and stasis. Salmonella bacteriuria, with or without bacteremia, is very common in patients with schistosomiasis. Treatment requires both antischistosomal and anti-Salmonella agents.

Tuberculosis (TB) of the kidney results from hematogenous spread but is relatively rare in developing countries. Unlike most other extrapulmonary manifestations of the disease, TB of the kidney does not become manifest until 5-15 years after the primary infection. Constitutional symptoms are uncommon, and most patients present with symptoms of bladder irritation. Initially, pyuria is observed, and, with progression of the disease, proteinuria and blood may be observed as well. Repeated urine samples should be sent for mycobacterial culture. A loss of calyceal architecture and ureteric obstruction may be observed on imaging studies. Concurrent pulmonary disease is present in 5% of patients, and the tuberculin test rarely is helpful. Antituberculous medicines should be administered for 6 months. If the ureter is obstructed, corticosteroids have been advocated; if obstruction persists, surgical intervention is necessary.

Mortality/Morbidity:

The mortality associated with acute uncomplicated cystitis among women aged 20-60 years appears to be negligible. A longitudinal cohort study of Swedish women showed a higher mortality among women with a history of UTI compared with age-matched women without this history (37% versus 28% in 10 y, P<0.001). These cohorts were not matched for other mortality-related factors, making it difficult to attribute the increased mortality to UTIs.

In contrast, the morbidity in terms of quality of life and economic measures is tremendous. Each episode of UTI in a young woman results in an average of 6.1 days of symptoms, 1.2 days of decreased class/work attendance, and 0.4 days in bed.

Groups at risk for UTIs associated with calculi include those with dysfunctional voiding, urinary intestinal diversion, indwelling urinary catheters, and vesicoureteral reflux.

Race: No racial predilection exists.

Sex: Uncomplicated UTIs are much more common among women than men when matched for age. A study of Norwegian men aged 21-50 years showed an approximate incidence of 0.0006-0.0008 infections per person-year, compared with approximately 0.5-0.7 per person-year in similarly aged women in the United States.

Renal carbuncles are more common in men than women by a ratio of 3:1 and are most common in the second to fourth decades of life. The right kidney is involved most commonly (63%).

Renal corticomedullary abscesses affect men and women equally; xanthogranulomatous pyelonephritis affects more women than men.

Age: The incidence of UTI in women tends to increase with increasing age. Several peaks above baseline correspond with specific events, including an increase among women aged 18-30 years (associated with honeymoon cystitis and pregnancy). Older adults have is a higher incidence of renal corticomedullary abscesses. This article does not discuss UTIs in children.

CLINICAL

History:

Acute urethritis

o This topic is addressed in greater detail in Urethritis. The symptoms of acute urethritis overlap with those of cystitis, including acute dysuria and urinary hesitancy.

o Urethral discharge is much more suggestive of urethritis, while bladder-related symptoms, such as urgency, polyuria, and incomplete voids, are more consistent with cystitis.

o Fever may be a component of urethritis-related syndromes (eg, Reiter syndrome, Behçet syndrome) but rarely is observed in acute cystitis.

Acute cystitis

o The symptoms of dysuria, urgency, hesitancy, polyuria, and incomplete voids also may be accompanied by urinary incontinence, gross hematuria, and suprapubic or low back pain.

o The predominant complaints relate to the inflamed bladder mucosa. Constitutional symptoms, such as fever, nausea, and anorexia, are rare or mild.

Acute pyelonephritis

o Unlike urethritis and cystitis, pyelonephritis may present with a paucity of lower urinary tract symptoms.

o The classic triad of fever, costovertebral angle pain, and nausea and/or vomiting may be present, though not necessarily occurring together temporally.

o Hematuria may occur but is more suggestive of nephrolithiasis in the presence of localizing back or flank pain.

o Fever and vomiting may suggest gastroenteritis. Patients also may present with right upper quadrant pain radiating to the back, mimicking cholecystitis or pancreatitis.

Complicated urinary tract infections

o UTIs associated with calculi may be insidious or asymptomatic. Patients may present with recurrent UTIs, abdominal pain, fever, gross hematuria, urinary fistulae, renal failure, or urosepsis.

o Patients with renal corticomedullary abscesses present with chills, fever, and flank or abdominal pain. Patients may have dysuria and/or nausea/vomiting. Leukocytosis may be present. Bacteriuria, pyuria, hematuria, or proteinuria may be present as the intrarenal abscesses drain in the collecting system, but the urinalysis results may be normal in as many as 30% of patients. Bacteremia may be observed in acute focal or multifocal bacterial nephritis.

o Patients with perinephric abscesses most commonly present with chills, fever, flank or abdominal pain, and dysuria. The physical examination is notable for flank and costovertebral angle tenderness and possibly a palpable mass.

o Renal cortical abscess patients may present with chills, fever, and flank or abdominal pain. Patients may present with a flank mass or a bulge in the lumbar region. Some have abnormal results on lung examination of the affected side (dullness to percussion, rales). Blood and urine culture results usually are negative, but the white blood cell count often is elevated.

o In patients with SCI, signs and symptoms suggestive of a UTI are malodorous and cloudy urine, muscular spasticity, fatigue, fevers, chills, and autonomic instability. Patients with lesions above T6 may exhibit autonomic dysreflexia to noxious stimuli (such as an overdistended bladder). The sympathetic response below the level of injury is uninhibited, producing severe vasoconstriction and reflexive bradycardia. If the patient is febrile, this may appear as a pulse-temperature dissociation.

Physical:

Acute cystitis

o Abnormal physical examination findings generally are lacking in women with acute cystitis. Patients may demonstrate some suprapubic tenderness to palpation.

o The pelvic examination reveals no abnormalities unless another process, such as vaginitis, is mimicking or occurring simultaneously with cystitis.

Acute pyelonephritis

o Fever in a young woman with symptoms referable to the urinary tract supports a diagnosis of pyelonephritis. Unilateral or bilateral costovertebral angle tenderness may be present.

o A pelvic examination may reveal findings suggestive of pelvic inflammatory disease, such as cervical motion tenderness or vaginal discharge.

o The abdominal examination may reveal upper quadrant tenderness, but peritoneal symptoms should not be present in acute uncomplicated pyelonephritis.

Patients with perinephric abscesses most commonly present with fever, chills, and flank tenderness; they may have a palpable mass.

Causes: E coli causes 70-95% of both upper and lower UTIs. The remainder of infections is composed of various organisms, including S saprophyticus, Proteus species, Klebsiella species, Enterococcus faecalis, other Enterobacteriaceae, and yeast. Some species are more common in certain subgroups, such as S saprophyticus in young women.

Sexual intercourse contributes to increased risk, as does use of a diaphragm and/or spermicide. Women who are elderly, pregnant, or have preexisting urinary tract structural abnormalities or obstruction carry a higher risk of UTI.

Most complicated UTIs are nosocomial in origin. The most common pathogens include E coli, enterococci, P aeruginosa, Candida species, and Klebsiella pneumoniae.

Calculi related to UTIs most commonly occur in women who experience recurrent UTIs with Proteus, Pseudomonas, and Providencia species.

Perinephric abscesses are associated most commonly with E coli, Proteus species, and S aureus but also may be secondary to Enterobacter, Citrobacter, Serratia, Pseudomonas, and Klebsiella species. More unusual causes include enterococcus, Candida species, anaerobes, Actinomyces species, and Mycobacterium tuberculosis. Twenty-five percent of infections are polymicrobial.

Candiduria is defined as more than 1,000 CFU of yeast from 2 cultures. Candida albicans, which is germ tube positive, is the usual culprit. Germ tube–negative Candida species (tropicalis, parapsilosis, glabrata, lusitaniae, krusei) are less common.

Patients with SCI develop UTIs with microorganisms that form dense biofilms on the bladder wall; thus, these infections are difficult to eradicate. Organisms that commonly cause infections include Proteus, Pseudomonas, Klebsiella, Serratia, and Providencia species, along with enterococci and staphylococci. Approximately 70% of infections are polymicrobial.

DIFFERENETIALS

Appendicitis Behcet Disease Bladder Cancer Bladder Stones

Bladder Trauma Chlamydial Genitourinary Infections Cholangitis Cholecystitis Colovesical Fistula Common Pregnancy Complaints and Questions Cystitis, Nonbacterial Diverticulitis Emphysema Emphysematous Pyelonephritis Enterobacter Infections Enterococcal Infections Escherichia Coli Infections Gardnerella Gastroenteritis, Bacterial Glomerulonephritis, Acute Gonococcal Infections Herpes Simplex Interstitial Cystitis Klebsiella Infections Mycoplasma Infections Nephrolithiasis Nephrolithiasis: Acute Renal Colic Pancreatitis, Acute Pneumonia, Bacterial Pneumonia, Community-Acquired Proteus Infections Providencia Infections Pseudomonas Aeruginosa Infections Pyelolithotomy Pyelonephritis, Acute Pyelonephritis, Chronic Pyonephrosis Renal Cell Carcinoma Renal Corticomedullary Abscess Renal Transplantation (Medical) Renal Transplantation (Urology) Schistosomiasis Sepsis, Bacterial Septic Shock Serratia Shock and Pregnancy Shock, Distributive Subacute Thyroiditis Trichomoniasis Tuberculosis Tuberculosis of the Genitourinary System Ureaplasma Infection Ureteral Injury During Gynecologic Surgery Ureteral Stricture Ureteral Trauma Ureterocele Ureterolithotomy Ureteropelvic Junction Obstruction Ureteroscopy Urethral Prolapse

Urethral Syndrome Urethritis Urinary Diversions and Neobladders Urinary Tract Infection, Females Urinary Tract Infections in Pregnancy Urinary Tract Obstruction Urologic Imaging Without X-rays: Ultrasound, MRI, and Nuclear Medicine Urothelial Tumors of the Renal Pelvis and Ureters Vaginitis Vesicoureteral Reflux Vesicovaginal Fistula Vesicovaginal and Ureterovaginal Fistula Xanthogranulomatous Pyelonephritis

Other Problems to be Considered:

Consider any condition involving flank/back pain or abdominal/pelvic pain.

The differential diagnosis for infectious causes of sterile pyuria includes perinephric abscess, urethral syndrome, renal TB, and fungal infections of the urinary tract system.

Noninfectious causes of pyuria include uric acid and hypercalcemic nephropathy, lithium and heavy metal toxicity, sarcoidosis, interstitial cystitis, polycystic kidney disease, genitourinary malignancy, and renal transplant rejection

Lab Studies:

In the 1980s, many experts felt that urine cultures were unnecessary in young women with cystitis complaints because almost all of these were caused by pan-susceptible isolates of E coli. However, since 1998, resistant isolates of E coli have emerged (in numbers as high as 20% in some communities). Trimethoprim-sulfamethoxazole (TMP-SMZ) resistance has been associated with concomitant resistance to other antibiotics. Consider obtaining urine cultures in the new millennium.

Urine specimens may be obtained by suprapubic aspiration, catheterization, or midstream clean catch. Bacteriuria, especially with many squamous cells without pyuria suggests contamination or colonization; some women may need to be catheterized to obtain a clean specimen. Although midstream urine specimens have been advocated, one randomized trial showed that the rate of contamination was not excessive in young women who urinated into a container without cleansing the perineum or discarding the first urine output.

Dipstick testing should include glucose, protein, blood, nitrite, and leukocyte esterase. A microscopic evaluation of the urine sample for white blood cell (WBC) counts, red blood cell (RBC) counts, and cellular or hyaline casts should be performed. In the office, a combination of clinical symptoms with dipstick and microscopic analysis showing pyuria and/or positive nitrite/leukocyte esterase tests can be used as presumptive evidence of UTI.

The most accurate method to measure pyuria is counting leukocytes in unspun fresh urine using a hemocytometer chamber; greater than 10 WBC/mL is considered abnormal. Counts determined from a wet mount of centrifuged urine are not reliable measures of pyuria. A noncontaminated specimen is suggested by a lack of squamous epithelial cells. Pyuria is a sensitive (80-95%) but nonspecific (50-76%) method of diagnosing UTI.

White cell casts may be observed in conditions other than infection, and they may not be observed in all cases of pyelonephritis. If the patient has evidence of acute infection and white cell casts are present, the infection likely represents pyelonephritis. A spun sample (5 mL at 2000 revolutions per min [rpm] for 5 min) is best used for evaluation of cellular casts.

Leukocyte esterase is a dipstick test that can rapidly screen for pyuria; it is 57-96% sensitive and 94-98% specific for identifying pyuria.

Nitrite tests detect the products of nitrate reductase, an enzyme produced by many bacterial species. These products are not present normally unless a UTI exists. This test has a sensitivity and specificity of 22% and 94-100%, respectively. The low sensitivity has been attributed to enzyme-deficient bacteria causing infection or low-grade bacteriuria.

Microscopic hematuria is found in about half of cystitis cases; when found without symptoms or pyuria, it should prompt a search for malignancy. Other things to be considered in the differential include calculi, vasculitis, renal TB, or glomerulonephritis. In a developing country, hematuria is suggestive of schistosomiasis, which can be associated with salmonellosis and squamous cell malignancies of the bladder. For more information on this interesting topic, the reader is referred to the article on Schistosomiasis.

Proteinuria commonly is observed in infections of the urinary tract, but the proteinuria usually is low grade. More than 2 grams of protein per 24 hours suggests glomerular disease.

Urine culture remains the criterion standard for the diagnosis of UTI. Collected urine should be sent for culture immediately; if not, it should be refrigerated at 4°C. Two culture techniques (dip slide, agar) are widely used and accurate. The 1999 Infectious Disease Society of America (IDSA) consensus limits for cystitis and pyelonephritis in women are more than 1000 CFU/mL and more than 10,000 CFU/mL, respectively, for clean-catch midstream urine specimens. Note that any amount of uropathogen grown in culture from a suprapubic aspirate should be considered evidence of a UTI. Approximately 40% of patients with perinephric abscesses have sterile urine cultures.

If a Gram stain of an uncentrifuged, clean-catch, midstream urine specimen reveals the presence of 1 bacterium per oil-immersion field, it represents 10,0000 bacteria/mL of urine. A specimen (5 mL) that has been centrifuged for 5 minutes at 2000 rpm and examined under high power after Gram staining will identify lower numbers. In general, a Gram stain has a sensitivity of 90% and a specificity of 88%.

Patients with spinal cord injury

o Diagnosing a UTI in a patient with an SCI is difficult. In these patients, suprapubic aspiration of the bladder is the criterion standard for diagnosing a UTI, although it is not performed often in clinical practice.

o All of these patients have some degree of bacteruria, but not all are actively infected. The diagnosis of significant bacteriuria, per the 1992 consensus statement of the National Institute on Disability and Rehabilitation Research (NIDRR), is any detectable concentration of a uropathogen collected from a patient with SCI and with an indwelling catheter. For patients utilizing intermittent catheterization, the definition of significant bacteriuria is 100 CFU/mL or more.

o The optimal method to diagnose pyuria in a patient with SCI has not been determined. More than 50 WBC per high-power field (hpf) is a reasonable indicator of high-level pyuria and has been associated with increased morbidity.

Approximately 70% of patients with corticomedullary abscesses have abnormal urinalysis findings, whereas those with renal cortical abscesses usually have normal findings. Two thirds of patients with perinephric abscesses have an abnormal urinalysis.

Other lab tests

o The WBC count usually is elevated in patients with complicated UTI. The WBC count may or may not be elevated in patients with uncomplicated UTI. Patients with complicated UTIs may have anemia, which is observed in 40% of patients with perinephric abscesses.

o Some patients have findings of electrolyte abnormalities, and 25% of patients with perinephric abscesses have azotemia.

o Bacteremia is associated with pyelonephritis, corticomedullary abscesses, and perinephric abscesses. Approximately 10-40% of patients with pyelonephritis or perinephric abscesses have positive results on blood culture. Bacteremia is not necessarily associated with a higher morbidity or mortality in women with uncomplicated UTI.

o Cervical swabs may be indicated.

Imaging Studies:

No imaging studies are indicated in the routine evaluation of cystitis or pyelonephritis. Women with acute pyelonephritis should be considered for imaging if they continue to have symptoms or clinical progression despite standard antimicrobial therapy for their infection. Complicated UTIs may require imaging. Options include a simple kidneys, ureter, and bladder (KUB) radiograph; a renal ultrasound; a CT scan; an MRI; nuclear imaging; and angiograms. Urologic intervention may be required, including intravenous pyelograms (IVPs) and ureterograms (ie, retrograde and percutaneous).

A renal ultrasound is a useful imaging modality in patients with complicated UTIs, and it may be performed at the bedside in a patient who is hemodynamically unstable. It is relatively inexpensive, does not involve radiation, and iodinated contrast is not needed. A renal abscess may appear as a fluid-filled mass with a thick wall. Acute focal bacterial nephritis appears as a poorly defined mass with low-amplitude echoes and disruption of the corticomedullary junction. Xanthogranulomatous pyelonephritis images reveal stones in approximately 70% of patients. Ultrasound findings may be falsely negative in 36% of perinephric abscesses. A drawback to ultrasound is the difficulty in differentiating renal abscess from tumor; it also is difficult to interpret in a patient who is obese.

Renal angiography may help differentiate renal abscess from renal tumor because an abscess often has increased peripheral vascularization (the remainder of the mass is avascular).

Nuclear studies

o Gallium (Ga) scans also may be used in the workup of a complicated UTI. The patient is injected with a transiently radioactive substance and returns 1-3 days

later. The emitted radiation provides an image, which, although it lacks precise anatomic detail, does provide functional information. A subtraction technique using Ga citrate and technetium (Tc) glucoheptonate needs to be performed to differentiate intrarenal abscess from tumor, obstruction, and severe pyelonephritis.

o An indium-111–labeled WBC scan can help to diagnose infection in persons with autosomal-dominant polycystic kidney disease.

For complicated UTIs, computed tomography (CT) scans provide the best definition, and the information is available quickly. Drawbacks to CT scans include some exposure to irradiation and the need for iodinated contrast. Abscesses should appear as low-density masses with contrast enhancement of the wall from inflamed/dilated blood vessels. Acute focal bacterial nephritis has a lobar distribution of inflammation, wedge-shaped hypodense lesions (postcontrast), and masslike hypodense lesions in severe infections. Xanthogranulomatous pyelonephritis may appear as large renal calculi, nonfunctioning kidneys, contrast enhancement around low attenuation areas, thickening of Gerota fascia, and spherical areas of low attenuation.

Patients with spinal cord injuries with more than 2 symptomatic UTIs within 6 months should be evaluated to rule out high-pressure voiding, vesicoureteral reflux, and the presence of stones. Evaluations often include urodynamic studies, nuclear scanning, renal ultrasound, voiding cystourethrography, abdominal CT scans, IVP, and/or cystoscopy.

Procedures:

The consulting urologist may wish to perform an IVP, cystoscopy, or a ureterogram (either retrograde or percutaneous)

TREATMENT

Medical Care: For adult women with acute bacterial cystitis who are otherwise healthy and not pregnant, single-dose therapy generally is less effective than a longer duration of the same antimicrobial agent. Most antimicrobial agents administered for 3 days are as effective as the same drug administered for a longer duration, with exceptions being nitrofurantoin and beta-lactams as a group.

TMP-SMZ for 3 days is considered the current standard therapy for bacterial cystitis. TMP-SMZ works as well as fluoroquinolones, which are more expensive. In 1999, to postpone the emergence of quinolone resistance, IDSA guidelines for UTI did not recommend quinolones as initial empiric therapy, except in communities with high rates (ie, over 10-20%) of uropathogen resistance to TMP-SMZ. Quinolones should be used for patients with known TMP-SMZ allergies, known TMP-SMZ–resistant pathogens, or those failing a TMP-SMZ regimen.

Drug selection could be facilitated if resistance patterns among uropathogens could be predicted clinically. Studies have compared women with UTI caused by TMP-resistant bacteria with women with TMP-sensitive isolates. After multivariate analysis, the strongest risk factor was current or recent use of TMP-SMZ; current use of any antibiotic, estrogen exposure, diabetes, and recent hospitalization also were significant. Rates of fecal colonization with TMP-SMZ–resistant E coli are increased in those who have recently been to Mexico, children in daycare centers, and in family members of those recently treated for a UTI.

Cystitis

o Cystitis in older women or infection caused by S saprophyticus is less responsive to 3 days of therapy; therefore, 7 days of therapy is suggested.

o Bladder analgesia using phenazopyridine 200 mg tid should be considered in women with severe dysuria. Duration of therapy should be limited to 2 or 3 days to ensure clinical improvement of symptoms.

Pyelonephritis o Fewer firm data are available on which to base sound treatment

recommendations for pyelonephritis. For young women who are not pregnant with normal urinary tracts, 14 days of therapy is appropriate.

o Mild infections can be managed with oral fluoroquinolones or TMP-SMZ. Women who should be considered for outpatient treatment include those with mild-to-moderate infection, those with easy access to follow-up appointments, and women without significant nausea or vomiting.

o Patients presenting with acute pyelonephritis can be treated with a single dose of a parenteral antibiotic followed by oral therapy, provided they are monitored within the first 48 h. A study of febrile, nonpregnant women presenting with symptoms of acute pyelonephritis found that 25% were hospitalized. These patients tended to be older and have diabetes, higher temperatures, and vomiting. Eighty percent of the outpatients were treated with a single parenteral dose of ceftriaxone or gentamicin, followed by oral therapy (usually TMP-SMZ). Twelve percent returned with persistent symptoms, most in the first day; most of these were admitted.

o Hospitalize patients with more severe infection and treat with a parenteral fluoroquinolone, an aminoglycoside (with or without ampicillin), or an extended-spectrum cephalosporin (with or without an aminoglycoside). Treat gram-positive cocci with ampicillin/sulbactam (with or without an aminoglycoside).

o Patients who relapse despite adequate therapy who lack anatomic abnormalities should be treated for 6 weeks. If a new pathogen causes infection, then another 2-week course should be effective.

Urinary tract infections associated with calculi o For UTIs associated with calculi, treatment ranges from observation to

nephrectomy. o The preferred method of treatment is surgical (see Surgical Care). Mere

observation is not recommended, as the mortality is 28% versus 7.2% in the surgically treated group. Antibiotic therapy should be used in conjunction.

o Although food and vitamin supplements that are rich in phosphorus and magnesium are advisable, remember that magnesium (and other divalent cations) can chelate quinolones, preventing their absorption from the gut.

o Acidifying agents have been used. Ascorbic acid does not significantly decrease urinary pH, and ammonium chloride provides only temporary acidification.

o Urease inhibitors are effective in reducing stone formation, but long-term use is fraught with neurosensory, hematologic, and dermatologic adverse effects.

Renal carbuncles o For renal carbuncles, surgical drainage once was the only treatment. However,

modern antibiotics alone often are curative. A semisynthetic penicillin, cephalosporin, quinolone, or vancomycin is recommended.

o Generally, parenteral antibiotics should be administered for 10-14 days, followed by oral therapy for 2-4 weeks. Fever should resolve within 5-6 days and pain within 24 hours.

o If patients do not respond within 48 hours, percutaneous (or open) drainage should be performed.

Acute, focal, and multifocal bacterial nephritis o Acute, focal, and multifocal bacterial nephritis should respond to antibiotics within

1 week. An extended-spectrum penicillin, cephalosporin, or quinolone should be used. A beta-lactam and an aminoglycoside also may be considered.

o Parenteral therapy should be used first, followed by at least 2 weeks of oral therapy. Those with large abscesses (ie, >5 cm), obstructive uropathy, advanced age, and urosepsis may not respond to antimicrobial therapy alone and require percutaneous drainage.

o Patients with severely damaged renal parenchyma, xanthogranulomatous pyelonephritis, or patients who are elderly and have sepsis may require nephrectomy.

Perinephric abscesses o Perinephric abscesses are associated with a high mortality rate (ie, 20-50%) and

require percutaneous or surgical drainage and antibiotics. o An aminoglycoside and an antistaphylococcal penicillin should be used. An

extended-spectrum beta-lactam also may be used. o Antibiotics should be modified based on culture results.

Spinal cord injury and urinary tract infections o Antibiotics should be reserved for patients with clear signs and symptoms of UTI. o Oral fluoroquinolones are the drugs of choice for empiric treatment of acute UTIs. o Options for hospitalized patients include parenteral fluoroquinolones, ampicillin

and gentamicin, imipenem plus cilastatin, third-generation cephalosporins, beta-lactam/beta-lactamase inhibitor combinations, or the aminoglycosides.

o Duration of therapy generally is 7-14 days, but 4-5 days may be acceptable for patients who are mildly symptomatic and who are closely monitored.

o If a patient fails to respond, then another culture should be obtained and an imaging study should be considered to rule out persistent infection, stone disease, and anatomic abnormalities causing obstruction.

o Treatment of asymptomatic patients is more controversial. While urine cultures with low bacterial counts often become sterile without treatment, some patients with ASB develop chronic infections secondary to bacterial biofilms. Some suggest that first episodes of ASB should be treated if significant bacteriuria (ie, more than 10,000 CFU/mL) is accompanied by pyuria (ie, more than 8-10 leukocytes/hpf).

Surgical Care:

Urinary tract infections associated with infected calculi

o Treatment ranges from observation to nephrectomy. Hydronephrosis is a concern (see Image 3).

o Surgical options include extracorporeal shock wave lithotripsy (ESWL), endoscopic methods, percutaneous methods, or open surgery.

o Mere observation is not recommended; the mortality associated with observation is 28%, versus 7.2% in the surgically treated group. Appropriate antibiotic therapy should be used as well.

Consultations: A pharmacokinetics consultation is suggested when using aminoglycosides or vancomycin. Urologic consultation is essential in patients with complicated UTIs. Other consultations depend on the patient's underlying state of health and may include an obstetrician,

gynecologist, endocrinologist, nephrologist, neurologist, and neurosurgeon. Infectious disease input is essential for unusual or resistant pathogens or hosts who are immunocompromised. Consultation with the patient's primary care provider is suggested.

Diet:

Hydration to accentuate unidirectional clearance of bacteruria is recommended, especially if an obstruction was relieved recently. Drinking cranberry juice (10 oz/d) may offer some benefit and does not appear to be harmful. One recent study found less recurrence of UTIs in women who drank 50 cc of cranberry-lingonberry concentrate daily for 6 months. The mechanism of action of cranberry juice is not clear. It is bacteriostatic, an effect probably due to hippuric acid. Another mechanism may involve suppression of E coli fimbriae by proanthocyanidins (tannins). Ascorbic acid (vitamin C) does not cause significant urinary acidification.

For complicated UTIs associated with struvite calculi, foods and vitamin supplements rich in phosphorus and magnesium are advised.

Remember that divalent cations (eg, magnesium, iron, calcium, zinc) can chelate oral fluoroquinolones, preventing their absorption from the gut.

MEDICATION

The goals of pharmacotherapy are to eradicate the infection, reduce morbidity, and prevent complications.

Drug Category: Antibiotics -- Empiric antimicrobial therapy should cover all likely pathogens in the context of this clinical setting. The prolonged or repeated use of antibiotics may result in fungal or bacterial overgrowth of nonsusceptible organisms, superinfections, or infections with C difficile.

Antibiotics sometimes are used in combination. Sometimes these combinations work against each other (ie, are antagonistic); examples would include beta-lactams (such as penicillin) and tetracyclines. Antagonism is defined as at least a 99% decrease in killing by the combination (when compared with the most active antimicrobial alone).

Synergism is when a combination of antibiotics has a significantly greater effect than would be expected from the sum of the separate drugs (ie, over a 99% increase in killing). Aminoglycosides and either beta-lactams or vancomycin are considered synergistic combinations. Because no single drug is considered bactericidal for the enterococcus, some might prefer to use synergistic combinations when treating enterococcal UTIs.

Trimethoprim (Proloprim, Trimpex) -- Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens, such as Enterobacteriaceae and S saprophyticus. Resistance usually is mediated by decreased cell permeability or alterations in the amount or structure of dihydrofolate reductase. Demonstrates synergy with the sulfonamides, potentiating the inhibition of bacterial tetrahydrofolate production.

Ampicillin (Omnipen, Principen, Totacillin, Polycillin) -- Impairs cell wall synthesis in actively dividing bacteria; binds to and inhibits penicillin-binding proteins (PBPs).

Gentamicin (Garamycin, Gentacidin) -- Bactericidal aminoglycoside antibiotic that inhibits bacterial protein synthesis. Activity against various aerobic gram-negative bacteria, as well as E faecalis and staphylococcal species. Most commonly used with or without ampicillin to treat acute pyelonephritis in the hospitalized patient when Enterococcus species are a concern. Only aminoglycoside with appreciable activity against gram-positive organisms

Cefixime (Suprax) -- Third-generation oral cephalosporin with broad activity against gram-negative bacteria, including Enterobacteriaceae, by inhibiting cell wall synthesis. Has shown poor activity against staphylococcal and enterococcal species. Cefixime compared favorably to a quinolone in one study.

Cefpodoxime proxetil (Vantin) -- Extended-spectrum oral cephalosporin with bactericidal activity against gram-positive and gram-negative bacteria, including S aureus (not MRSA) and S saprophyticus. Active agent in vivo is cefpodoxime. Beta-lactams, in general, have been given an "E, I" rating in the 1999 IDSA guidelines for treating UTIs.

Nitrofurantoin (Furadantin, Macrobid, Macrodantin) -- Synthetic nitrofuran that interferes with bacterial carbohydrate metabolism by inhibiting acetylcoenzyme A. Bacteriostatic at low concentrations (5-10 mcg/mL) and bactericidal at higher concentrations. Bactericidal against uropathogens such as S saprophyticus, E faecalis, and E coli; possesses no activity against Proteus, Serratia, or Pseudomonas species. Received a "B, I" rating in the 1999 IDSA guidelines for treating UTIs. Manufactured in different forms to facilitate durable urine concentrations: macrocrystals (Macrodantin), microcrystal suspension (Furadantin), and a combined preparation (Macrobid). Achieves no appreciable concentrations in the prostate, kidney, or blood

Deterrence/Prevention:

Approximately 25% of women with acute cystitis develop recurrent UTIs. The number of recurrences experienced varies for each woman (range, 0.3-7.6 episodes per year), and recurrences often cluster in time. The majority of recurrent infections are from bacteria colonizing the fecal or periurethral reservoirs. The 3 main risk factors are (1) the frequency of sexual intercourse, (2) the use of a spermicide and diaphragm, and (3) the loss of estrogen's effect in the vagina and periurethral structures.

o Women who develop a UTI within 2 weeks of a treated UTI either have a new infection or they have a recurrence of the original uropathogen. The latter is supported by cultures growing the same species, especially if it is biotyped or shares the same antimicrobial sensitivities.

o Looking for a source of persistent infection, such as a structural abnormality (eg, calculus, abscess, cystic disease) is prudent.

Women with recurrent UTIs (less than 2-3 per y) may benefit from behavioral modification and a program of self-initiated antibiotics.

o Behavioral modifications are generally easy, low-risk, and low-cost maneuvers. Methods include urge-initiated voiding, postcoital voiding, increased fluid intake, and the daily consumption of cranberry juice.

o Patients using a spermicide should consider alternative methods of contraception.

o Self-initiated antibiotics may be an acceptable alternative for women with recurrent UTIs. The clinician should educate the patient about the warning signs of a persistent or worsening infection despite therapy. A recent study showed that women with a history of at least 2 UTIs in the past year were capable of self-

diagnosing and treating UTIs. Uropathogens were isolated in 84% of 172 UTIs; clinical and microbiologic cures were achieved in about 95% of episodes.

Women with recurrent UTIs (more than 3 per y) should be considered for more aggressive prophylactic regimens in addition to the behavioral modifications.

o Women who associate their recurrent UTIs with sexual intercourse should be offered postcoital prophylaxis. This involves taking a single dose of an effective antimicrobial (eg, nitrofurantoin 50 mg, TMP-SMZ 40/200 mg, or cephalexin 500 mg) after sexual intercourse.

o Continuous antimicrobial prophylaxis may be required in women who fail a postcoital regimen, do not associate frequent UTIs with a modifiable cause, or who are at risk for recurrent complicated UTIs. Regimens include TMP-SMZ (40/200 mg qhs or 3 times per wk), nitrofurantoin (50-100 mg qhs or 3 times per wk), norfloxacin (200 mg qhs or 3 times per wk), and trimethoprim (100 mg qhs or 3 times per wk).

o These regimens have been shown to be safe and effective, even after 5 years of use. However, after 6-12 months, a trial without the medication is warranted because as many as 30% of women experience a prolonged UTI-free period. Prophylaxis may be reinstituted if the patient again develops recurrent UTIs.

Women who are postmenopausal with recurrent UTIs may benefit from estrogen replacement, either systemically or locally. Estriol in a vaginal cream (0.5 mg every pm for 2 wk, then twice weekly) significantly reduced the incidence of recurrent UTI; the effect probably is related to the restoration of lactobacilli, which replace Enterobacteriaceae and decrease the vaginal pH.

For patients with SCI, the efficacy of prophylaxis with TMP-SMZ or nitrofurantoin has been demonstrated. The possibility of developing resistant organisms is a concern, especially in an institutional setting.

o One option includes the use of methenamine (1 g tid), alternating q2mo with nitrofurantoin (50-100 mg bid). Methenamine is converted into formic acid, which is bacteriocidal. Oral ascorbic acid therapy has not been shown to confer much benefit.

o Risk can be decreased by the use of intermittent catheterization. Urine cultures should be obtained periodically, and prophylactic or long-term antibiotic therapy may be considered if over 10,000 CFU/mL and pyuria are noted (even in the absence of symptoms).

o Reflex bladder pressures greater than 50 cm H2O should be avoided through the use of alpha-blockers, anticholinergics, transurethral sphincterotomy, or electrical stimulation.

o Using a 6% bleach solution to clean reusable leg bags and seat covers decreases the rates of infection and ASB.

Neither cefuroxime nor ciprofloxacin was shown to reduce the rate of bacteriuria (about 20%) after lithotripsy.

The American Heart Association recommends antimicrobial prophylaxis to prevent bacterial endocarditis in patients with moderate-to-high–risk cardiac conditions. High-risk conditions include prosthetic valves, previous bacterial endocarditis, complex cyanotic congenital heart diseases, and surgically constructed systemic pulmonic shunts. Moderate-risk conditions include most other congenital heart diseases, hypertrophic cardiac myopathy, and mitral prolapse with regurgitation. For patients with moderate- or high-risk cardiac conditions, urologic procedures warranting prophylaxis include cystoscopy and urethral dilatation; prophylaxis is not recommended for inserting a Foley

catheter in a patient with uninfected urine. No good evidence supports using such regimens for prophylaxis for patients with prosthetic joints; this is an area that needs further research and study.

o Regimens for high-risk patients include ampicillin (or vancomycin) plus gentamicin. Ampicillin is administered as 2000 mg IM or IV within 30 minutes of starting the procedure; 6 hours later, 1000 mg of ampicillin (or amoxicillin PO) is administered once. Gentamicin is dosed at 1.5 mg/kg IV or IM (not to exceed 120 mg) and is administered only once with the first dose of ampicillin. For patients allergic to ampicillin, 1000 mg of vancomycin is administered only once, IV over 1-2 hours; it should be completed within 30 minutes of starting the procedure.

o Regimens for moderate-risk patients include amoxicillin or vancomycin. Amoxicillin is administered only once as 2000 mg PO 1 hour before the procedure. For patients allergic to amoxicillin, 1000 mg of vancomycin is administered only once, IV over 1-2 hours; it should be completed within 30 minutes of starting the procedure.

Complications:

Bacteremia, sepsis, shock, and death have all been discussed.

Prognosis:

The prognosis for most women with cystitis and pyelonephritis is good; about 25% of women with cystitis will experience a recurrence.

The prognosis for emphysematous pyelonephritis is not as good and will be discussed in Special Concerns.

Infected cysts in polycystic kidney disease respond to treatment slowly.

Special Concerns:

Catheters

o Nosocomial infections develop in about 5% of patients admitted to hospitals, and UTIs account for 40% of these infections. Two to 4% of these patients become bacteremic, with a mortality rate of 12.5%.

o Once a catheter is placed, the daily incidence of bacteriuria is 3-10%. Ten to 30% of patients with short-term catheterization (ie, 2-4 d) develop bacteriuria and are asymptomatic. Ninety to 100% of patients with long-term catheterizations develop bacteriuria.

o Pathogenesis: The presence of potentially pathogenic bacteria and an indwelling catheter predisposes to the development of a nosocomial UTI. The bacteria may gain entry into the bladder during insertion of the catheter, during manipulation of the catheter/drainage system, around the catheter, and after removal. Enteric pathogens are responsible most commonly, but Pseudomonas species, Enterococcus species, S aureus, coagulase-negative staphylococcus, Enterobacter species, and yeast also are known to cause infection. Proteus and Pseudomonas species are the organisms most commonly associated with biofilm growth on catheters.

o Risk factors: The most important risk factor for bacteriuria is the presence of a catheter. Eighty percent of infections are related to a catheter while 5-10% are related to genitourinary manipulation. Catheters inoculate organisms into the bladder and promote colonization by providing a surface for bacterial adhesion and causing mucosal irritation. Risk factors for bacteriuria in patients who are catheterized include longer duration of catheterization, colonization of the drainage bag, diarrhea, diabetes, absence of antibiotics, female gender, renal insufficiency, errors in catheter care, catheterization late in the hospital course, and immunocompromised or debilitated states.

o Diagnosis: Symptoms generally are nonspecific; most patients present with fever and leukocytosis. Significant pyuria generally is represented by greater than 50 WBC/hpf. Colony counts on a urine culture range from 100-10,000. Infections may be polymicrobial.

o Prevention At least nine steps can be taken to prevent catheter-associated UTIs.

These steps can postpone a UTI for weeks but are not likely to be successful in chronically catheterized patients. Catheterization should be avoided when not required (catheters were found to be unnecessary in 41-58% of patient-days) and should be terminated as soon as possible. Suprapubic catheters are associated with a lower risk of UTI. Patients who require long-term catheterization are more satisfied, but mechanical complications are increased. Contraindications include bleeding disorders, previous lower abdominal surgery or irradiation, and morbid obesity. Intermittent catheterization is an option, but most become bacteriuric within a few weeks as the incidence is 1-3% per insertion.

Aseptic indwelling catheter insertion and a properly maintained closed-drainage system are essential. Urinary catheters coated with silver also reduce the risk (silver alloy seems to be more effective than silver oxide). Another approach is the Bard Lubricath, which has a hydrophilic coating that decreases tissue irritation and nosocomial UTIs. It is reasonable to use these more expensive catheters in those who are at highest risk.

Receiving systemic antimicrobial drug therapy has been shown repeatedly to lower the risk for developing a UTI in catheterized patients; most benefit was observed in those catheterized for 3-14 days. Most hospitalized patients already are receiving antibiotics for other reasons. Disadvantages include creating resistant organisms. Because many of these infections occur in clusters, good handwashing before and after catheter care is essential.

o Treatment: Removal of the catheter is adequate in some patients with bacteriuria. If bacteriuria persists 48 hours after removal of the Foley catheter, antibiotics should be started. Antibiotic therapy is directed at the pathogen(s) isolated in the culture. Patients with chronic indwelling catheters who are febrile and not bacteremic should be treated with a 3- to 5-day course of antibiotics. If a patient is bacteremic, then a 10- to 14-day course of antibiotics is recommended.

Pregnancy

o ASB occurs in 5-10% of pregnant women. More than 100,000 CFU/mL of a single uropathogen is the classic definition of ASB, but more recent data support 10,000 CFU/mL from a clean-catch specimen.

o ASB most commonly appears between the ninth and 17th weeks of pregnancy. ASB predisposes to preterm labor, intrauterine growth retardation, low–birth weight infants, anemia, amnionitis, and hypertensive disorders of pregnancy.

o Risk factors include sexual activity, increasing age and parity, diabetes, lower socioeconomic class, a history of UTIs, sickle cell disease, and

structural/functional abnormalities. Cystitis and pyelonephritis are inevitable complications of ASB.

o The recommendation is to screen pregnant women at their first prenatal visit and during the third trimester and not again, unless their initial test result is positive or they develop symptoms. Cystitis occurs in 0.3-1.3% of pregnancies but does not appear to be related to ASB. Acute pyelonephritis occurs in 1-2% of pregnancies. Complications of pyelonephritis include pulmonary edema and acute respiratory distress syndrome, transient renal dysfunction, anemia, preterm delivery, and low–birth weight infants.

o ASB must be treated and not merely observed. Treatment of ASB decreases the risk of persistent bacteriuria from 86-11%, with a significant reduction in the risk of acute pyelonephritis. Sulfonamides, cephalosporins, nitrofurantoin, and broad-spectrum penicillins have been shown to be effective. A 4- to 7-day course of therapy is recommended for treating ASB and cystitis. Sulfonamides just before birth may cause fetal hyperbilirubinemia, while trimethoprim early in pregnancy is teratogenic.

o Repeat cultures should be obtained during pregnancy given the high risk of relapse. After the second occurrence, nitrofurantoin, amoxicillin, or a cephalosporin is recommended for suppression until after delivery. Hospitalization is indicated for pyelonephritis with nausea/vomiting, evidence of sepsis, or for patients with contractions. Empiric parenteral regimens include a cephalosporin, such as ceftriaxone, or gentamicin plus ampicillin (or a derivative of penicillin). When using an aminoglycoside, the risk of ototoxicity in the fetus must be considered.

o Antibiotic regimens should be changed based on culture results. Patients may be changed to oral therapy once they are afebrile and able to tolerate an oral regimen. Urolithiasis, a structural abnormality, or an abscess should be considered if a patient fails to respond to appropriate therapy.

Urinary tract infections in patients with renal transplants

o UTIs are the most common type of infection following renal transplantation. UTIs occur in 30-50% of renal transplant patients and frequently are silent.

o UTIs may, but do not always, predispose the patient to graft loss or rejection. Infection of the allograft may lead to life-threatening bacteremia. Patients are most susceptible the first 2 months following transplantation. Triggering factors include vesicoureteral reflux and immunosuppression.

o An unusual bacterium, Corynebacterium urealyticum (ie, CDC group D2), has been reported to cause encrusted pyelitis and cystitis in these patients. Treatment of UTIs in renal transplant patients is preferably with either TMP-SMZ or a quinolone.

o ASB should be treated for 10 days. Parenteral antibiotics should be used for severe infections. The duration of antibiotics for severe infections should be 4-6 weeks.

o Antibiotic prophylaxis is valuable in patients undergoing renal transplantation. TMP-SMZ (1 PO qd), beginning 2-4 days after surgery and continuing for 4-8 months, reduced the incidence of UTIs from 38-8% (especially after the catheter was removed), cut febrile hospital days and bacterial infections (during and after hospitalization) in half, and reduced graft rejection.

Yeast and fungi

o Removal of a Foley catheter is essential for clearance of funguria. If the catheter is still needed, replace it (preferably a day later).

o Treatment options vary from topical treatment to systemic therapy. o Amphotericin-B bladder washes for 7 days provides a prompt but nonsustained

response. It does not treat systemic mycoses and is inconvenient for the nurse to administer. Amphotericin-B, 0.3 mg/kg IV for 1 dose is an option that provides a more sustained and systemic response.

o Fluconazole, 200 mg PO for 1 d followed by 100 mg PO qd for 4-7 d is a simpler option. This drug is effective against azole-responsive candida. Generally, azole-resistance is observed only in Candida krusei and Candida glabrata. Fluconazole provides a good long-term effect but takes a few days to clear the urine.

Diabetes mellitus o Complicated UTIs in patients who have diabetes include renal and perirenal

abscess, emphysematous pyelonephritis, emphysematous cystitis, fungal infections, xanthogranulomatous pyelonephritis, and papillary necrosis.

o Emphysematous pyelonephritis is a severe, necrotizing form of multifocal bacterial nephritis with gas formation within the renal parenchyma. Seventy to 90% of cases develop in patients with diabetes. Sixty percent of infections are secondary to E coli. Enterobacter aerogenes and Klebsiella, Proteus, Streptococcus, and Candida species also may play a role.

Three factors must be present for the development of renal emphysema—excess tissue glucose, impaired tissue perfusion, and a gas-producing bacterium. The gas may result from fermentation of necrotic tissue or from mixed acid fermentation by Enterobacteriaceae. Predisposing factors include diabetes mellitus, remote or recent kidney infection, and obstruction.

Patients may present with fever, chills, and nausea or vomiting. Half of patients have evidence of a flank mass on examination. Rarely, patients have crepitus over the thigh or flank.

Lab findings include leukocytosis, hyperglycemia, pyuria, and an elevated BUN and creatinine. A plain film of the abdomen may reveal gas in the kidneys in 85% of infections. A renal ultrasound also may help establish the diagnosis. If gas is visualized, then a CT scan should be performed to reveal if the gas is in the parenchyma or collecting system.

The mortality rate is 60% in cases in which the gas is localized to the renal parenchyma, regardless of treatment. The mortality is 80% if the gas has spread in the perinephric space and the patient is treated with antibiotics alone.

o Emphysematous pyelitis is defined as the presence of gas localized to the renal collecting system. Emphysematous cystitis is defined as air in the urinary tract.

Pathogenesis: More than 50% of these patients have diabetes. Obstruction of the collecting system generally is the rule in emphysematous pyelitis. The left kidney is involved twice as often as the right in emphysematous pyelitis. The most common infectious etiology is E coli, but other gram-negative organisms, S aureus, Clostridium perfringens, and Candida species also may be responsible.

Presentation: Patients with emphysematous pyelitis most commonly present with fever, chills, nausea and vomiting, and abdominal pain. Patients with emphysematous cystitis most commonly present with urinary frequency, urgency, and dysuria. Abdominal pain also may be present. Gross hematuria and pneumaturia are occasionally present.

Diagnosis: Leukocytosis and pyuria are observed in most patients. In half of the patients, azotemia and hyperglycemia are present. Abdominal films may reveal gas outlining the renal pelvis and in the ureters. Abdominal films may reveal air in the bladder wall or lumen. Renal ultrasound may reveal diffuse thickening of the bladder wall and

echogenicity. CT scans may reveal gas in the bladder wall with extension into the lumen. Cystoscopy may reveal blebs in the bladder mucosa.

Therapy: Antibiotics and relief of obstruction usually are sufficient. The mortality rate is 20%.

Papillary necrosis o Definition: Papillary necrosis is defined as focal or diffuse ischemic necrosis of

various segments of the renal medulla. o Pathogenesis: This entity is uncommon in people with diabetes, but, when

infections occur, more than one half are in people with diabetes. Other causes include sickle cell disease, analgesic abuse, pyelonephritis, renal transplant rejection, cirrhosis, and obstruction. Most infections are complicated by UTI and renal insufficiency.

o Two types of papillary necrosis have been described. In the medullary form, the fornices remain intact. In the papillary form, the entire papillary surface is destroyed.

o Presentation: Many patients present with fever, chills, and flank pain. The flank pain is secondary to the passage of sloughed papilla. Some patients may present with symptoms of obstruction or azotemia.

o Histology and/or radiologic studies may help make the diagnosis. The sloughed papillae may be obtained by straining the urine and sending for histology. The retrograde pyelogram is the radiologic procedure of choice, but ultrasound or CT scan also reveal the diagnosis. Findings of early renal papillary necrosis include a dilated calyceal fornix, retracted or irregular papillary tip, and extension of contrast into the parenchyma. A club-shaped cavity in the medulla or papilla may be formed in later disease. When a separated papilla is surrounded by contrast, a ring may be visualized; this is characteristic of papillary necrosis.

o Treatment: Antibiotics, drainage, and (occasionally) surgery are the mainstays of therapy. Antibiotics should cover E coli and Enterobacter, Proteus, and Klebsiella species.

o Treatment for more serious infections also should cover Pseudomonas and Enterococcus species. Initial therapy should not be with an oral regimen. Parenteral agents such as gentamicin, cefotaxime, ceftriaxone, ceftazidime, cefepime, mezlocillin, piperacillin, piperacillin-tazobactam, imipenem-cilastatin, meropenem, or ciprofloxacin should be used empirically pending the result of a urine culture. Parenteral therapy should be continued until the fever and other symptoms resolve. Duration of therapy generally is 14 days.

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