1. INFECTIONS OF THE GENITOURINARY TRACT DEPARTMENT OF UROLOGY IAŞI – 2013

2. INFECTIONS OF G-U TRACT EPIDEMIOLOGY  < 1 yr – bacteriuria: 2.7% M (phimosis), 0.7% F  1-5 yrs: 4.5% F, 0.5% M (congenital abnormalities; VUR or obstruction)  6-15 yrs (functional abnormalities: dysfunctional voiding)  16-35 yrs: F 20% (sexual intercourse and diaphragm use  36-65 yrs: F  (gynecologic surgery and bladder prolapse), M  (prostatic hypertrophy/obstruction, catheterization and surgery)  > 65 years:  (incontinence and chronic use of urinary catheters) PATHOGENESIS – bacterial entry (4)  ascending: periurethral bacteria  urinary tract; short female urethra + close proximity to the vaginal vestibule and rectum

3. INFECTIONS OF G-U TRACT  hematogenous – in immunocompromised patients and neonates; Staph aureus, Candida sp and Mycobacterium tuberculosis  lymphatogenous – spread through the rectal, colonic, and periuterine lymphatics  direct extension – intraperitoneal abscesses, vesico-intestinal or vesico-vaginal fistulas; relapsing infection from an inadequately treated focus in the prostate or kidney Host Defenses  unobstructed urinary flow (washout of ascending bacteria)  urine specific characteristics (osmolality, urea concentration, organic acid concentration and pH)  inhibit bacterial growth and colonization; factors that inhibit bacterial adherence (glycoprotein)

4. INFECTIONS OF G-U TRACT  presence of foreign bodies (stones, catheters, stents) allows the bacteria to hide from the host defenses  cells of the urinary tract secrete chemoattractants (interleukin-8) to recruit neutrophils to the area and limit tissue invasion  specific serum and urinary antibodies produced by the kidney   bacterial opsonization and phagocytosis and  bacterial adherence  normal flora of the periurethral area (lactobacillus) or the prostate (Zn)  in children, VUR  allow bacteria to be inoculated into the upper tract and the infection to progress  aging:  susceptibility –  incidence of obstructive uropathy (M), alteration in the vaginal and periurethral flora (F), soiling of the perineum from fecal incontinence, neuromuscular diseases, increased instrumentation and bladder catheterization

5. INFECTIONS OF G-U TRACT Bacterial Pathogenic Factors  Escherichia coli – uropathogens = limited number of O, K and H serogroups  increased adherence to uroepithelial cells [fimbriae (pili)], resistance to the bactericidal activity of human serum, production of hemolysin (  tissue invasion and makes iron available for the infecting pathogens) and  expression of K capsular antigen (protects from phagocytosis by neutrophils) CAUSATIVE PATHOGENS  80% of the uncomplicated cystitis and pyelonephritis – E coli; less common – Klebsiella, Proteus, Enterobacter spp and enterococci  hospital-acquired UTIs – a wider variety of causative organisms, including Pseudomonas and Staphylococcus spp  children – Klebsiella and Enterobacter spp

6. INFECTIONS OF G-U TRACT DIAGNOSIS  relies on urinalysis and urine culture, from a voided or bagged specimen, suprapubic aspiration or from a urinary catheter  occasionally, localization studies may be required to identify the source of the infection Urinalysis  rapid screen for UTIs (urine dipstick) – leukocyte esterase (white blood cells) and urinary nitrite  microscopic examination for WBCs (> 3 per HPF) and bacteria Urine Culture  quantitative culture for specific bacteria: > 100,000 CFU/mL (to exclude contamination)  clinically significant UTI can occur with < 100,000 CFU/mL bacteria

7. INFECTIONS OF G-U TRACT Localization Studies  upper urinary tract localization: bladder irrigated with sterile water, ureteral catheter placed into each ureter, specimen collected from the renal pelvis  in M, infection in the lower urinary tract (Meares and Stamey); specimen collected at the beginning of the void (urethra), midstream specimen (bladder), prostate massaged and void (prostate) ANTIBIOTICS  goal – to eradicate the infection by selecting the appropriate antibiotics that would target specific bacterial susceptibility

8. INFECTIONS OF G-U TRACT  general principles for selecting the appropriate antibiotics  infecting pathogen (antibiotic susceptibility, single-organism vs. poly-organism infection, pathogen vs. normal flora, community vs. hospital-acquired infection)  patient (allergies, underlying diseases, age, previous antibiotic therapy, other medications currently taken, outpatient vs. inpatient status, pregnancy)  the site of infection (kidney vs. bladder vs. prostate)  certain antimicrobial agents – adjusted in the presence of liver or renal diseases  in patients with recurrent UTIs or those at risk for UTI (children with VUR) – prophylactic antibiotics

9. INFECTIONS OF G-U TRACT  trimethoprim-sulfamethoxazole (TMP-SMX) – except Enterococcus and Pseudomonas spp; interferes with the bacterial metabolism of folate; highly effective and relatively inexpensive; adverse reactions: hypersensitivity reactions, rashes, gastrointestinal upset, leukopenia, thrombocytopenia and photosensitivity  fluoroquinolones – broad spectrum of activity, except Streptococci species and anaerobic bacteria; interfere with the bacterial DNA gyrase, preventing bacterial replication; highly effective but relative expensive; adverse reactions: mild gastrointestinal effects, dizziness and lightheadedness; should not be used in pregnant patients and in children (damage to developing cartilage)

10. INFECTIONS OF G-U TRACT  nitrofurantoin – good activity against most gram-negative bacteria (except Pseudomonas and Proteus spp), Staphylococci and Enterococci species; inhibits bacterial enzymes and DNA activity; highly effective and relative inexpensive; adverse reactions; gastrointestinal upset, peripheral polyneuropathy and hepatotoxicity, pulmonary hypersensitivity reaction and interstitial changes  aminoglycosides – used in the treatment of complicated UTI; highly effective against most gram-negative bacteria; combined with ampicillin, are effective against enterococci; inhibit bacterial DNA and RNA synthesis; adverse effects: nephrotoxicity and ototoxicity; regimen is directed toward obtaining higher peak and lower trough levels (more effective microbial killing while reducing toxicity)

11. INFECTIONS OF G-U TRACT  cephalosporins – good activity against most uropathogens; inhibit bacterial cell wall synthesis; adverse reactions: hypersensitivity and gastrointestinal upset; in children with febrile UTI/pyelonephritis, oral third-generation cephalosporins (cefixime) are safe and effective  aminopenicillins (amoxicillin and ampicillin) – good activity against Enterococci, Staphylococci, E coli and Proteus mirabilis; addition of ß-lactamase inhibitors (clavulanic acid) makes more active against the gram-negative bacteria; adverse reactions; hypersensitivity, gastrointestinal upset and diarrhea

12. INFECTIONS OF THE KIDNEY ACUTE PYELONEPHRITIS  inflammation of the kidney and renal pelvis, and its diagnosis is usually made clinically Presentation and Findings  chills, fever and costovertebral angle tenderness; often accompanying lower-tract symptoms (dysuria, frequency and urgency); sepsis may occur (20-30% of urosepsis)  E coli is the most common causative organism (80%), Klebsiella, Proteus, Enterobacter, Pseudomonas, Serratia and Citrobacter spp.; gram-positive bacteria (Streptococcus faecalis and S aureus) Imaging  renal US – rule out concurrent urinary tract obstruction; enlarged kidney, hypoechogenic parenchyma

13. INFECTIONS OF THE KIDNEY  CT scan (not necessary unless diagnosis is unclear or patient is not responding to therapy): constriction of peripheral arterioles and reduced perfusion of the affected renal segments (segmental, multifocal or diffuse – areas of reduced signal density), renal enlargement, attenuated parenchyma and a compressed collecting system  radionuclide study (99mTc-DMSA): detecting the perfusion defects of pyelonephritis Management  depends on the severity of the infection; toxicity because of associated septicemia  hospitalization  empiric therapy – i.v. ampicillin and aminoglycosides or amoxicillin with clavulanic acid or a third-generation cephalosporin

14. INFECTIONS OF THE KIDNEY  parenteral therapy – until the patient defervesces; if bacteremia is present, parenteral therapy should be continued for an additional 7-10 days, then oral treatment for 10-14 days  patients who are not severely ill, outpatient treatment with oral antibiotics: fluoroquinolones or TMP-SMX for 10-14 days EMPHYSEMATOUS PYELONEPHRITIS  necrotizing infection – presence of gas within the renal parenchyma or perinephric tissue  80-90% have diabetes; the rest – associated with urinary tract obstruction (calculi) or papillary necrosis Presentation and Findings  fever, flank pain and vomiting that fails initial management with parenteral antibiotics; pneumaturia may be present: bacteria – E coli, Klebsiella pneumoniae, Enterobacter cloacae

15. INFECTIONS OF THE KIDNEY Radiographic Imaging  diagnosis: gas overlying the affected kidney on a plain abdominal radiograph (KUB); CT scan – more sensitive in detecting the presence of gas in the renal parenchyma than renal US Management  essential – prompt relief of urinary obstruction (percutaneous drainage), control of blood glucose, fluid resuscitation and parenteral antibiotics  mortality: 11-54%; poor prognostic factors: high serum creatinine level, low platelet count, the presence of renal/perirenal fluid + bubbly/loculated gas pattern or gas in the collecting system  nephrectomy may be required; 3-4 weeks of parenteral antibiotic therapy is usually required

16. INFECTIONS OF THE KIDNEY RENAL/PERINEPHRIC ABSCESS  severe infection that leads to liquefaction of renal tissue, subsequently sequestered  rupture out into the perinephric space  perinephric abscesses; extend beyond the Gerota's fascia  paranephric abscesses  hematogenous spread of staphylococci (infected skin lesions)  abscesses in the renal cortex  patients with diabetes, undergoing hemodialysis or i.v. drug abusers – high risk  abscesses due to gram-positive bacteria are less prevalent; those caused by E coli or Proteus species are becoming more common – formed in the corticomedullary junction, in conjunction with underlying urinary tract abnormalities (stones or obstruction)

17. INFECTIONS OF THE KIDNEY Presentation and Findings  fever, flank or abdominal pain, chills and dysuria  flank mass may be palpated  urinalysis – usually WBCs; normal in approx. 25% of the cases  urine cultures – 1/3; blood cultures – 1/2 Imaging  US – anechoic mass within or displacing the kidney/echogenic fluid collection that blends with the fat within Gerota's fascia  CT scan – enlarged kidney with focal areas of hypoattenuation  mass with a rim of contrast enhancement ("ring" sign); thickening of Gerota's fascia, stranding of the perinephric fat or obliteration of the surrounding soft-tissue planes

18. INFECTIONS OF THE KIDNEY Management  appropriate antibiotic therapy – empiric therapy with broad- spectrum antibiotics (ampicillin or vancomycin + aminoglycoside or third-generation cephalosporin)  w/o respose within 48 h  percutaneous drainage under CT or US guidance  culture of the drained fluid  still not resolved  open surgical drainage or nephrectomy  evaluation for underlying urinary tract abnormalities (stone or obstruction) XANTHOGRANULOMATOUS PYELONEPHRITIS  form of chronic bacterial infection of the kidney – hydronephrotic and obstructed  severe inflammation and necrosis of the kidney parenchyma

19. INFECTIONS OF THE KIDNEY  foamy lipid-laden histiocytes (xanthoma cells)  renal clear cell carcinoma Presentation and Findings  history of urolithiasis (35% )  flank pain, fever, chills and persistent bacteriuria  physical examination – flank mass often palpated  urinalysis – WBCs and protein, urine culture – E coli, Proteus  anemia, hepatic dysfunction (50%) Imaging  CT scan (most reliable) - large heterogeneous, reniform mass; renal parenchyma marked with multiple water-density lesions (dilated calyces or abscesses); inflammatory process extend to perinephric fat, retroperitoneum and adjacent organs (psoas muscle, spleen, colon or great vessels)

20. INFECTIONS OF THE KIDNEY  renal US – enlarged kidney with a large central echogenic area and anechoic parenchyma  misdiagnosed as a renal tumor – similar appearances Management  nephrectomy  diagnosis is made pathologically PYONEPHROSIS  bacterial infection of a hydronephrotic & obstructed kidney  suppurative destruction of renal parenchyma (loss of renal function)  sepsis may rapidly ensue  rapid diagnosis and management Findings  high fever, chills, flank pain & pyuria

21. INFECTIONS OF THE KIDNEY  bacteriuria & leukocyturia (may be absent with complete obstruction!)  US – persistent echoes in the lower part of the collecting system, fluid-debris level with echoes that shift with positional changes, strong echoes with acoustic shadowing (air in the collecting system), dilated collecting system, renal or ureteral calculi  IVU – opacities, nonfunctional kidney Management  immediate institution of antibiotic therapy and drainage of the infected collecting system (percutaneous nephrostomy or ureteral stent)  then, treatment of the cause (urolithiasis, UPJ obstruction etc.) or nephrectomy

22. INFECTIONS – BLADDER ACUTE CYSTITIS  urinary infection of the lower urinary tract (bladder); F > M  irritative voiding symptoms (dysuria, frequency & urgency)  low back and suprapubic pain, hematuria, and cloudy/foul- smelling urine  urinalysis – WBCs, hematuria; urine culture  management – short course of oral antibiotics (TMP-SMX, nitrofurantoin, fluoroquinolones) – 3-5 d RECURRENT CYSTITIS/UTI  caused by bacterial persistence (  removal of the infected source) or reinfection with another organism (  preventive therapy)

23. INFECTIONS – BLADDER  bacterial persistence  imaging (US, IVU, cystoscopy, CT scan, bacterial localization studies, retrograde pyelograms)  bacterial reinfection  evidence of vesicovaginal or vesicoenteric fistula Management  bacterial persistence  surgical removal of the infected source (urinary calculi)  bacterial reinfection  prophylactic antibiotics (low-dose continuous or intermittent self-start), surgical repair of fistulas  related to sexual activity  frequent emptying of the bladder & single dose of antibiotic, after intercourse  intravaginal estriol, lactobacillus vaginal suppositories and cranberry juice taken orally

24. INFECTIONS – PROSTATE ACUTE BACTERIAL PROSTATITIS  inflammation of the prostate associated with a UTI  ascending urethral infection or reflux of infected urine from the bladder into the prostatic ducts Presentation and Findings  abrupt onset of fever, chills, malaise, arthralgia, myalgia, lower back/rectal/perineal pain and urinary symptoms (frequency, urgency, dysuria  acute urinary retention)  DRE – tender, enlarged irregular and warm gland  urinalysis – WBCs, occasionally hematuria  leukocytosis; PSA   ! urethral catheterization & prostatic massage should be avoided  bacteremia

25. INFECTIONS – PROSTATE  US – residual urine; TRUS – non-responsive to conventional therapy Management  trimethoprim or fluoroquinolones (high drug penetration into prostatic tissue) for 4-6 wks. (prevent complications – chronic prostatitis, abscess formation)  sepsis, immunocompromised pts., acute urinary retention or significant medical comorbidities  hospitalization and parenteral antibiotics (amoxyclav + aminoglycoside)  urinary retention  suprapubic catheter CHRONIC BACTERIAL PROSTATITIS  relapsing, recurrent UTI caused by the persistence of pathogen in the prostatic fluid, despite antibiotic therapy

26. INFECTIONS – PROSTATE  dysuria, urgency, frequency, nocturia and low back/perineal pain  others are asymptomatic, but have bacteriuria  DRE is often normal; occasionally, tenderness, firmness or prostatic calculi  urinalysis – WBCs and bacteriuria; PSA may be   diagnosis – identification of bacteria from prostate expressate or urine specimen after a prostatic massage (4-cup test)  TRUS – if prostatic abscess is suspected Management  antibiotic therapy – similar to acute bacterial prostatitis, but up to 3-4 mo.  alpha blocker – to reduce symptom recurrences

27. INFECTIONS – PROSTATE  cure is not often achieved  poor penetration of antibiotic into prostatic tissue & isolation of the bacterial foci within the prostate  recurrent episodes of infection  suppressive antibiotic (TMP- SMX 80/240 mg daily, nitrofurantoin 100 mg daily, or ciprofloxacin 250 mg daily)  refractory disease  ? TUR-P EPIDIDYMITIS  most cases < 35 years – due to sexually transmitted organisms (N gonorrhoeae, C trachomatis); in children and older men – E coli  epididymis  testis

28. INFECTIONS – PROSTATE Presentation and Findings  severe scrotal pain – may radiate to the groin or flank; scrotal enlargement (inflammation of epididymis/testis or reactive hydrocele); symptoms of urethritis, cystitis or prostatitis  physical examination – enlarged and red scrotum; thickened spermatic cord  urinalysis – WBCs and bacteria in the urine or urethral discharge; blood analysis – leukocytosis  epididymitis  acute testicular torsion  scrotal Doppler US – presence of blood flow in the testis  radionuclide scanning – uptake of the tracers into the center of the testis

29. INFECTIONS – PROSTATE  scrotal US – enlarged epididymis with increased blood flow; reactive hydrocele or testicular involvement Management  antibiotic treatment  gonococcal  ceftriaxone (250 mg i.m.) or fluoroquinolones (ciprofloxacin 250 mg or norfloxacin 800 mg)  nongonococcal  tetracycline or erythromycin (500 mg 4 times daily) or doxycycline (100 mg twice daily) for 7-14 days  bed rest, scrotal elevation, nonsteroidal anti-inflammatory agents  treatment of the sexual partner  abscess  open drainage  chronic, relapsing epididymitis, scrotal pain  epididymectomy

30. SPECIFIC INFECTIONS  specific infections – caused by specific organisms, clinically unique disease, specific pathologic tissue reactions TUBERCULOSIS  young adults (60% of pts. – age 20-40); M > F Etiopathogenesis  Mycobacterium tuberculosis  lungs  hematogenous route  GU organs  kidney  bladder  prostate  bladder, epididymis  testis  renal parenchyma (no symptoms)  calyces  pus and organisms discharged into urine  symptoms (of cystitis)

31. SPECIFIC INFECTIONS  infection of the pelvic mucosa and the ureter  stricture and (uretero)hydronephrosis  caseous breakdown of renal tissue + Ca laid down in the reparative process  fibrosis of ureter  shortened and straightened  "golf-hole" ureteral orifice (incompetent valve)  bladder – vesical irritability; tubercles form, coalesce & ulcerate (bleeding); fibrosis & contraction of the bladder (marked frequency); ureteral reflux or stenosis  ureterohydronephrosis  extensive epididymal infection  abscess formation  spontaneous rupture  permanent sinus of the scrotal skin

32. SPECIFIC INFECTIONS Pathology  granuloma (basic lesion in TB) – aggregation of histiocytic cells (vesicular nucleus and clear cell body), that can fuse with neigh- boring cells  epithelioid reticulum; at the periphery are large cells with multiple nuclei (giant cells)  virulence of organism  resistance of patient  caseation and cavitation  healing by fibrosis and calcification  bladder – tubercles can be seen endoscopically (white or yellow raised nodules surrounded by a halo of hyperemia)

33. SPECIFIC INFECTIONS Clinical findings  symptoms – vesical in origin (cystitis)  nonspecific complaints – generalized malaise, fatigability, low- grade persistent fever, night sweats  epididymis – painless or mildly painful swelling (including vas deferens), chronic draining sinus  evidence of extraGU tuberculosis (lungs, bone, lymph nodes, tonsils, intestines) Laboratory  persistent pyuria, acid pH, without organisms on usual cultures  acid-fast stain (Ziehl-Neelsen), cultures (Löwenstein-Jensen)

34. SPECIFIC INFECTIONS X-Ray findings  KUB – calcifications in the renal parenchyma  IVU – “moth-eaten” ulcerated calyces; obliteration of calyces; (U)HN due to ureteral stenosis from fibrosis; abscess cavities that connect with calyces; multiple ureteral strictures, with shortening and straightening of the ureter; non-functional kidney due to complete ureteral occlusion or renal destruction (autonephrecto- my)  retrograde ureteropyelogram  US, CT Instrumental examination  cystoscopy – tubercles or ulcers  biopsies + pathology

35. SPECIFIC INFECTIONS Treatment  Medical (2-3 m, 7/7 + 4-3 m, 2-3/7)  isoniazid (INH), 200–300 mg orally once daily;  rifampin (RMP), 600 mg orally once daily;  ethambutol (EMB), 25 mg/kg daily for 2 months, then 15 mg/kg orally once daily;  streptomycin, 1 g intramuscularly once daily;  pyrazinamide, l.5–2 g orally once daily.  Surgical – urinary diversion or augmentation cystoplasty (ileocystoplasty, ileocecocystoplasty, sigmoidocystoplasty), nephrectomy, epididymectomy