INFECTIONS OF THE GENITOURINARY TRACT DEPARTMENT OF UROLOGY IAŞI – 2013

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

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)

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

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

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

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

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

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)

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)

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

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

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

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

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

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)

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

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

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)

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

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

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)

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

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

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

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

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

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

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

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)

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

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)

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)

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

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