Infection & Inflammation

UTI: Definitions & Classification

• Uncomplicated UTI — non-pregnant women with no known anatomical/functional abnormality
  • S. saprophyticus — coagulase-negative, novobiocin-resistant gram-positive coccus
    • → ~10% of symptomatic lower UTIs in young, sexually active women
    • Rarely infects men or the elderly
    • 2nd most common isolate in acute uncomplicated cystitis after E. coli; susceptible to nitrofurantoin and TMP-SMX
  • Urgency → cystitis, not vaginitis (vaginitis = irritative voiding + vaginal irritation, but no frequency, urgency or suprapubic pain)
• Complicated UTI — all men; pregnant women; or non-pregnant women with functional/anatomical abnormality
• No need to treat asymptomatic UTI unless pregnant or before a urological procedure
  • EAU: the urological procedure must breach the mucosa
  • Asymptomatic man with bacteria but no pyuria → at most asymptomatic bacteriuria → observe and reassure
  • Unremarkable history → cystoscopy and upper tract imaging not mandatory
    • Persistent urease producer (e.g. Proteus mirabilis) → exclude stones
    • Men → DRE
• Pyuria without bacteriuria → warrants evaluation for TB, stones, cancer
  • Mycobacterial culture indicated only for sterile pyuria

CIC & ileal conduit

• CIC: asymptomatic bacteriuria in up to 50% → observation only
  • No antibiotics, antibiotic-coated catheters or sterile CIC
  • Treatment breeds resistant organisms and raises Clostridium difficile colitis risk
  • Pyuria + bacteriuria on CIC → treat only for symptoms:
    • Increased leakage between catheterizations (worsening voiding)
    • Fever
    • Flank/abdominal discomfort
    • Not malodorous urine or MRSA in urine
• Ileal conduit: ~three-quarters of urine specimens culture-positive (bacterial colonization)
  • Asymptomatic Proteus → treat to reduce stone formation (Proteus also makes upper-tract deterioration more likely)
  • Other asymptomatic organisms → observe

Treatment — Uncomplicated UTI (Cystitis)

• Women:
  • Fosfomycin 3 g single dose, OR
    • Fosfomycin trometamol, oral → 1 day of therapy; one dose sustains high urinary concentrations for ~3 days
  • Nitrofurantoin 100 mg BID × 5 days
  • Bactrim 160/800 BID × 3 days
    • ~80% of E. coli sensitive
  • Oral fluoroquinolones less preferred → resistance as high as 50% in some communities
  • Resistance profile decides which agent, not how long
  • Young woman asymptomatic afterward → no follow-up or test-of-cure culture
• Men (cystitis):
  • Bactrim 160/800 BID × 7 days, OR
  • Ciprofloxacin 500 mg BID × 10–14 days (complicated UTI)
• Phenazopyridine alone → not adequate treatment for a symptomatic UTI

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Bacteriuria, Nitrites & Urease Organisms

• Pyuria = presence of ≥5 WBC or more (per HPF)
  • Leukocyte esterase → highest sensitivity for UTI, but low specificity
• Nitrite positive organisms (nitrate reductase +):
  • E. coli
  • Klebsiella
  • Proteus
  • Enterobacter
  • Serratia
  • Urinary nitrite = bacterial reduction of urinary nitrate → very high specificity
• Nitrite negative organisms:
  • Pseudomonas
  • Streptococcus
  • Pseudomonas — unlike Enterobacteriaceae (E. coli, Klebsiella, Proteus), cannot convert nitrate → nitrite → false-negative nitrite dipstick
  • Most gram-positives (enterococcus, staphylococcus) also nitrite-negative
  • Symptomatic + LE-positive pyuria but nitrite-negative → still treat presumptively
    • Keep Pseudomonas (aggressive pathogen) in mind
• Red urine with no RBCs and no hemoglobin/myoglobin → pigment, drug or dietary cause (e.g. beeturia) → hematuria workup not triggered

Urease-producing organisms → struvite stones (MAP)

• Stone-forming (urease +):
  • Staphylococcus (90%)
  • Proteus (90%)
  • Klebsiella
  • Enterobacter
  • Serratia
  • Morganella
  • Pseudomonas
  • Providencia
  • Candida humicola
  • S. aureus usually produces urease (>90% of isolates), as do Proteus spp., Providencia stuartii and Ureaplasma urealyticum
  • Four commonest urease producers: Proteus (most common), Klebsiella, Pseudomonas, S. aureus
  • Proteus mirabilis → organism most often linked to infection stones
  • E. coli is not a urea splitter despite being a common uropathogen (only rare E. coli produce urease)
• Mechanism: urease splits urea → ammonia + bicarbonate → urine alkalinization → promotes MAP (struvite) crystallization
  • Exam answer: urea → ammonia + carbon dioxide; ammonium precipitates with magnesium + phosphate as struvite
  • Bacteria also damage the urothelial glycosaminoglycan (GAG) layer → promote adherence and biofilm
  • Urine pH > 7.0 → suggests infection lithiasis (or renal tubular acidosis)
• Culture infected stones — half grow organisms different from the preoperative urine
• Spinal cord injury: renal stone rates 7–8× the general population
  • Urease-splitting infection is a significant risk factor
  • Struvite stones on an indwelling urethral catheter, unable to self-catheterize → come off the urethral catheter →
    • Sphincterotomy + condom catheter (less-invasive first choice)
    • Suprapubic drainage considered optimal
• Urostomy bleeding, encrustation, plaque →
  • Almost always chronic alkaline urine exposure (urea-splitting infection or device contamination) + poor appliance hygiene
  • Management:
    • Treat the UTI
    • Urinary acidification
    • Weak acidic cutaneous soaks
    • Acid-clean the collecting device
  • Appliance allergy and Candida → peristomal dermatitis instead

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Bacteriuria — Diagnostic Thresholds (MCU)

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Persistent / Severe Complicated UTI

• Severe complicated UTI → parenteral antibiotics 14–21 days
• Urological abnormalities causing persistent UTI:
  • Stones
  • Chronic bacterial prostatitis
  • Foreign body
  • Atrophic kidney
  • Diverticulum
  • Urachal cyst
  • Abscess
  • Recurrent UTI + lower pole stone + suspected UPJ obstruction → diuretic renal scan first (quantifies obstruction)
    • Obstruction confirmed → dismembered pyeloplasty + pyelolithotomy
    • No obstruction → ureteroscopy or PCNL
• Unresolved bacteriuria (same organism, similar resistance profile, never cleared) →
  • Most often initial resistance to the chosen drug → repeat culture + sensitivities and switch agent before imaging
  • Rarer causes:
    • Resistance emerging during therapy
    • 2 organisms with mutually exclusive susceptibilities
    • Azotemia
    • Papillary necrosis
    • Giant staghorn calculus
    • Noncompliance / malabsorption
• Mixed-flora UTI (E. coli, Pseudomonas, enterococcus) → suspect vesicoenteric fistula
  • Men >50 → commonest cause = diverticulitis with vesicocolic fistula
  • Crohn's disease → usually patients <40
• Catheter-associated UTI = complicated UTI
  • Catheter in place 2 weeks → replace or remove it and send urine culture before treating
  • Men → treat 10–14 days: 7 days is inferior to 14 days in males with systemic UTI (likely prostatic involvement)

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Sepsis

• Host response — innate cells:
  • Neutrophils → most abundant innate immune cell in peripheral blood (~60% of WBCs) · major cellular constituent of pus
  • BCG → cell-wall peptidoglycans bind TLR2 on resident bladder-wall immune cells → neutrophils = second major innate cell to arrive
  • Urothelial CXCL8 → powerful neutrophil chemoattractant
• Mediator of septic shock → endotoxin = lipopolysaccharide of the gram-negative outer membrane
  • Lipid A triggers the inflammatory cascade
  • Bacterial cell wall components, not secreted exotoxins, are primarily responsible
• Organisms → gram-negatives predominate in sepsis syndrome / septic shock: 30–80% of cases vs 5–24% gram-positives
  • Gram-negative uropathogens dominate urological sepsis
• Earliest signs:
  • Hyperventilation → most reliable early clinical indicator of septicemia; often precedes temperature extremes and chills
  • Resulting respiratory alkalosis → earliest metabolic change · early sign of septic shock
• Progression → hypoperfusion → metabolic acidosis
  • Later features:
    • Tachycardia
    • Oliguria
    • ↑ cardiac output
    • ↑ plasma norepinephrine
• Post-prostate biopsy sepsis → best initial therapy = imipenem (carbapenem), given the resistance pattern:

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Approach to Recurrent UTI

• Definition: ≥2 UTIs in 6 months OR ≥3 in 12 months
  • Single resolved episode → counseling only, no antibiotic prophylaxis

Workup

• Hx & PE + UA & culture + PVR
  • Diagnose recurrent cystitis by urine culture
  • Women <40 with no risk factors → no extensive routine workup (cystoscopy, full abdominal ultrasound)
  • Intermittent dysuria / urgency but no documented infection →
    • Culture during symptomatic episodes before any antibiotic prophylaxis
    • Hold off on cystoscopy / upper-tract evaluation
  • Man <45 → uroflow + PVR to rule out retention (not imaging) → low flow + raised PVR → add cystoscopy for stricture

Positive culture

• Positive culture → antimicrobial therapy → repeated infection, same species:
  • Yes (same species) → Bacterial persistence → urological evaluation (CT-U + cystoscopy) → removal of infection focus
  • No → Reinfection → assess risk factors
    • Risk factors present → urological evaluation (CT-U + cysto)
    • No risk factors → related to coitus?
      • Counsel on behavioral measures first (e.g. extra 1.5 L fluid daily in low-volume drinkers) → continuous or post-coital antibiotic prophylaxis only after non-antimicrobial measures fail
    • Yes → post-coital prophylaxis
      • Preferred when linked to intercourse → as effective as continuous low-dose, with much less total antibiotic exposure
      • Single dose, before or after intercourse: nitrofurantoin 50–100 mg · TMP-SMX (Bactrim) single or double strength · cephalexin 250 mg (not 500 mg)
    • No → low-dose prophylaxis OR self-start therapy
      • Continuous low-dose → eradicates introital + bowel uropathogens only while taken; host susceptibility unchanged → stopping returns recurrence risk to pre-treatment level

Reinfection and persistence

• Reinfection → recurrence after documented cure, no focus inside the urinary tract → bacteria reintroduced from outside
  • Most recurrent UTIs in women · source = ascent of fecal flora or reemergence from intracellular uroepithelial colonies
  • Longer interval than persistence → most occur >2 weeks and <5 months
  • Men → often signals a urinary tract abnormality
  • Consider vesicoenteric / vesicovaginal fistula with pneumaturia, fecaluria, diverticulitis, prior pelvic surgery or radiotherapy
• Bacterial persistence → same organism at short intervals from a focus inside the urinary tract (classically an infection stone)
  • → usually cured by removing the focus
• Prophylaxis prevents reinfections · suppression → reserved for a persistence focus that cannot be removed
• Antimicrobial treatment (none, short-term, long-term or prophylactic) alters only the time until recurrence → risk of recurrent bacteriuria stays the same

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Prevention & Modifiable Risk Factors

• Cranberry juice (36 mg or 200–750 mL daily) → blocks adherence of pathogens to uroepithelial cells
  • Reduces morbidity + time of recurrent bacteriuria, but risk of recurrence is the same
  • No substantive effect on urine pH, osmolality, secretory IgA or interleukin levels
  • Women with recurrent uncomplicated pan-sensitive E. coli UTIs → cranberry = prophylactic option
    • No routine cystoscopy or imaging
• Modifiable risk factors for bacterial persistence: check PVR, hydration, constipation
  • Healthy premenopausal woman with recurrent cystitis → ↑ fluid intake by 1.5 L/day = effective prophylaxis (RCT)
• Risk factors in women:
  • Major → sexual activity / intercourse · new partner within the past year
  • Also spermicides · recent antimicrobials · menopause · first-degree female relative with UTI
  • Young premenopausal women → intercourse, new partner and spermicide = recognized risk factors for recurrent cystitis
  • Spermicidal jelly / foam → markedly alters vaginal flora → E. coli colonization + post-coital bacteriuria
  • Not known to affect it: menstrual timing · oral contraceptives · partner condom use
• Not shown to help: cotton underwear · wiping away from the urethra
• Fluoroquinolone prophylaxis → reserved for bacterial resistance or allergy (black box warning)
• 2019 AUA recurrent UTI guideline → does not recommend D-mannose, vaginal lactobacillus suppositories or daily methenamine for prophylaxis
• Postmenopausal → consider vaginal estrogen
  • 2019 AUA → recommends vaginal estrogen in peri- and postmenopausal women
  • Next step in postmenopausal recurrent UTI → intravaginal estrogen: ↑ lactobacillus, ↓ vaginal pH → UTIs 5.9 → 0.5 per patient-year
  • Oral estrogen → controversial (systemic risks: stroke, blood clots)
  • Quinolone or nitrofurantoin prophylaxis → not the best choice (side effects)
• Institutionalized elderly women → perineal soiling from urinary + fecal incontinence → ascent of enteric uropathogens
  • E. coli still 75%
  • Incontinent nursing-home patients with recurrent UTI →
    • Continence care, skin + perineal hygiene, avoid unnecessary catheterization
    • Not antimicrobial prophylaxis
• CAUTI prevention → daily bacteriuria risk 3–7% per indwelling catheter
  • Closed drainage system → most effective measure · plus aseptic insertion, early removal, avoid unnecessary catheterization
  • Prophylactic antibiotics → may ↑ CAUTI + resistant organisms
  • Not shown to reduce infection: meatal cleansing · antibiotic bladder irrigation · hydrogen peroxide in the drainage bag

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Host & Bacterial Factors

• E. coli pili:
  • P pili → adhesion ability → pyelonephritis
    • Mannose-resistant · kidney tropism ("P" for pyelonephritis) · present in 91% of pyelonephritis strains vs 19% of cystitis strains
    • Encoded by the pap operon · bind renal glycolipid receptors
  • Type 1 pili → no adhesion
    • Exam answer: type 1 (mannose-sensitive) pili help early bladder colonization; by phase variation, P pili take over attachment in the kidney
• Urine bacterial growth inhibited by:
  • Diluted urine
  • High osmolality
  • Low pH
  • Other urinary host defenses:
    • High urea
    • Efficient voiding
    • Adherence inhibitors → Tamm-Horsfall protein, lactoferrin, oligosaccharides, mucopolysaccharides

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Cystitis — Treatment by Population

• Avoid Bactrim in pregnancy (1st trimester & 3rd trimester)
• Avoid nitrofurantoin in pregnancy (3rd trimester)
  • Limited to the 1st–2nd trimester → risk of neonatal hemolytic anemia
• 3rd-trimester cystitis → amoxicillin → penicillins are the safest antibiotics throughout pregnancy
• Asymptomatic bacteriuria in pregnancy → screen & treat when found
  • Treatment ↓ symptomatic UTI, low birthweight & preterm delivery; untreated → ↑ 3rd-trimester acute pyelonephritis
  • 3–7 day sensitivity-guided course (single-dose vs 2–7 days → no significant difference)
    • → then low-dose prophylaxis, esp. with a history of recurrent UTI
  • Exam answer: 1st trimester + penicillin allergy → nitrofurantoin → not a beta-lactam; its restrictions (G6PD deficiency, late pregnancy / neonatal hemolysis) don't apply early
• Avoid Bactrim with warfarin — also Cipro
• Follow-up urine culture after treatment recommended for older women & men

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Antimicrobial Therapy & Prophylaxis

Mechanisms & Coverage

• Cephalexin → 1st-gen cephalosporin (beta-lactam)
  • → inhibits cell wall synthesis → binds penicillin-binding proteins (transpeptidases) → blocks peptidoglycan cross-linking
  • → bactericidal vs actively dividing bacteria
• Fluoroquinolones (ciprofloxacin) → DNA gyrase inhibitor
  • → covers Enterobacteriaceae, P. aeruginosa, S. aureus & S. saprophyticus
  • Enterococci not reliably covered → poorer results in enterococcal prostatitis
  • Streptococcal coverage marginal; most anaerobes resistant → spares normal vaginal & bowel flora
• Fosfomycin → most uropathogens incl. most gram-negatives & VRE, limited cross-resistance → main gap = P. aeruginosa
• Enterococcus faecalis UTI → amoxicillin / ampicillin first-line if susceptible
  • Nitrofurantoin (incl. penicillin allergy) or fosfomycin also effective
  • Not reliably effective → fluoroquinolones, clindamycin, aminoglycosides, cephalosporins

Renal Dosing & Toxicity

• Most antimicrobials → wide therapeutic index → no dose adjustment until GFR <20 mL/min (exception: nephrotoxic agents, e.g. aminoglycosides)
• Renally cleared → levofloxacin, ciprofloxacin, TMP-SMX, amoxicillin, cephalexin
  • → with eGFR <25 mL/min adjust dose / interval, don't withhold
• Doxycycline → unlike most tetracyclines, eliminated mainly non-renally (hepatic/biliary & intestinal/fecal)
  • → usual dose in renal impairment, azotemia & dialysis
• Nitrofurantoin → contraindicated (not dose-adjusted) at eGFR ≤45 mL/min/1.73 m²
  • → accumulation ↑ toxicity + ↓ urinary delivery → treatment failure
  • Therapeutic levels only in urine → unsuitable for complicated UTI
  • Peripheral neuropathy → avoid in neurologically vulnerable patients (e.g. MS on clean intermittent catheterization)
    • Neuropathy risk ↑ →
      • Debilitated
      • Renal impairment
      • Anemia
      • Diabetes
      • Electrolyte imbalance
      • Vitamin B deficiency
• Trimethoprim → blocks tubular secretion of creatinine (normally 10% of removal; up to 35% at GFR 40–80 mL/min)
  • → serum creatinine ↑, true GFR unchanged
• Fluoroquinolone class toxicity →
  • Tendon & aortic rupture (each ~20 per 100,000)
    • Leg / ankle pain after cipro → Achilles tendinopathy / rupture → can begin during or weeks after the course → stop at first tendon pain
  • QT prolongation
  • CNS (dizziness, tremor, confusion, hallucinations)
  • Hypo- / hyperglycemia on antidiabetic drugs
  • Contraindicated in children, adolescents, pregnant / nursing women → collagen & cartilage toxicity damages developing cartilage

Allergy & Special Situations

• Cystitis + penicillin & sulfonamide allergy → fosfomycin single oral dose (neither beta-lactam nor sulfonamide)
  • Alternative → nitrofurantoin if CrCl ≥50 mL/min
• Afebrile cystitis + G6PD deficiency & significant renal insufficiency (e.g. stage 3 CKD)
  • → nitrofurantoin & TMP-SMX both contraindicated → fosfomycin
• After penicillin anaphylaxis → aztreonam can be given
  • Carbapenems & cephalosporins share hypersensitivity risk (cephalosporins usually safe after mild penicillin reactions)
  • Ampicillin immunogenically very similar to penicillin
  • No evidence that premedication (diphenhydramine + hydrocortisone) ↓ risk of giving a cephalosporin
• Severe pyelonephritis + penicillin anaphylaxis → gentamicin, even with renal insufficiency
  • → life-threatening infection outweighs nephrotoxicity (cephalosporins & carbapenems generally contraindicated)

Pregnancy & Neonates

• Febrile UTI in a jaundiced 3-week-old → empiric ampicillin → Enterococcus more frequent in early infancy, must be covered
  • Avoid ceftriaxone (<1 month of age or jaundice), TMP-SMX (jaundice), ciprofloxacin (contraindicated at this age; typically misses Enterococcus)

Warfarin Interactions

• Resuming warfarin (e.g. after TURP) → avoid cranberry juice
  • → inhibits intestinal flora → ↓ vitamin K production → ↑ warfarin effect
• Grapefruit juice → ↑ INR
• Cystitis antibiotic least likely to enhance warfarin → nitrofurantoin
• Potentiate warfarin →
  • Fluoroquinolones (e.g. ciprofloxacin)
  • TMP-SMX & other sulfonamides
  • Tetracyclines (e.g. doxycycline)
  • Metronidazole
• Can also interact → nitrofurantoin, fluconazole, amoxicillin-clavulanate
• Mechanisms:
  • ↓ hepatic metabolism → metronidazole
  • Displacement from protein binding → sulfonamides, nalidixic acid
  • ↓ gut-flora vitamin K synthesis → broad-spectrum oral agents, esp. tetracyclines

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Procedure Prophylaxis

• 10 host risk factors for postoperative infection →
  • Advanced age
  • Anatomic anomalies
  • Poor nutritional status
  • Smoking
  • Chronic corticosteroids
  • Immunodeficiency
  • Chronic indwelling hardware
  • Infected material
  • Distant coexistent infection
  • Prolonged hospitalization
• Diagnostic cystoscopy:
  • AUA-based rule → healthy, no host risk factors → no prophylaxis
  • Host risk factors (e.g. smoking, advanced age) → one preop oral dose only
    • → TMP-SMX (sulfamethoxazole 800 mg / trimethoprim 160 mg) or amoxicillin-clavulanate, not a continued course
  • EAU 2026 → strongly against prophylaxis for flexible / rigid urethrocystoscopy
    • → no ↓ systemic UTI (RR 1.12) but ↑ bacterial resistance (RR 1.73)
• TURP → single-dose cefazolin 2 g IV or TMP-SMX
  • Recurrent ESBL history doesn't change this if preop urine culture sterile
  • Long resection → redose cefazolin every 4 h
  • Alternatives → amoxicillin-clavulanate, aminoglycoside ± ampicillin, aztreonam ± ampicillin
• Intravesical onabotulinumtoxinA → UA + urine culture first
  • → document sterile urine (UTI a recognized risk; bacteriuria after a 100 U injection high)
  • Warn → limited duration of response, UTI risk, possible prolonged intermittent catheterization
  • Check baseline PVR & willingness to self-catheterize
• Catheter removal / trial of voiding → no routine prophylaxis (weak recommendation)
  • → inconsistent benefit across trials + more resistant isolates
  • If used (short-term catheter ≤14 days) → TMP-SMX; greatest benefit if >60 y & catheterized >5 days
  • Catheter-associated asymptomatic bacteriuria → not treated, except before a traumatic intervention (e.g. TURP)
    • A trial of voiding doesn't count

Prosthesis & Bite Infections

• Penile prosthesis infection → S. epidermidis commonest, then S. aureus, Candida albicans
  • → skin flora introduced at surgery → biofilm on device
  • Rates → 1–3% primary, 7–18% revision; antibiotic-coated devices ↓ infection 50–70%
• Human bite to genitalia →
  • Amoxicillin-clavulanate 875/125 mg BID until healing (moxifloxacin alternative)
    • → covers Eikenella corrodens, oral anaerobes, streptococci & staphylococci + irrigation & local wound care
  • Often no primary closure
  • Confirm tetanus status
  • Offer hepatitis B vaccine / immunoglobulin & HIV PEP per exposure risk

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Emphysematous Cystitis

• Cystitis (UTI) with air in the bladder, no recent instrumentation
• Treatment → antibiotics & drainage

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Fungal UTI (Candida)

• Candida albicans → sensitive to azole
  • Almost all urinary C. albicans isolates → fluconazole-sensitive
• Candida glabrata & krusei → Amphotericin
• Flucytosine → second-line, reserved for fluconazole-resistant Candida
  • Dose → 25 mg/kg QID × 2 weeks, reduced as creatinine clearance falls
  • Main drawback → rapid resistance when given alone (often during treatment) → combined with amphotericin B
• No need to treat asymptomatic candiduria unless:
  • Neutropenia / immunocompromised, low birth weight infants, or before urological procedure
• Asymptomatic candiduria often resolves with no treatment → just control predisposing risk
  • e.g. remove/exchange Foley, control diabetes

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Acute Pyelonephritis

• Triad: fever, chills, flank pain
• Serum procalcitonin → may help identify acute pyelonephritis in children
• Gram-negative endotoxin decreases ureteral peristalsis (as do pregnancy & ureteral obstruction) → stasis → promotes retrograde bacterial ascent
  • Endotoxin-induced stasis can dilate the ureter without mechanical obstruction
    • → hydronephrosis in pyelonephritis is not automatically a stone, but true obstruction must still be excluded
• Treatment depends on symptoms & improvement
• No sepsis or vomiting → imaging optional
  • Do culture first, treat as outpatient with oral abx (Cipro) × 7–10 days
  • Improved after 72 hr → continue treatment + urine culture on Day 4 of abx + urine culture 10 days off abx
  • No improvement after 72 hr → hospitalize + parenteral abx (Cipro) × 14–21 days + imaging + review culture + drain obstruction or abscess
• Sepsis → imaging + urine culture + blood culture
  • Start parenteral abx (Cipro) × 14–21 days
  • Improved after 72 hr → switch to oral abx + repeat urine culture on Day 4 & Day 10 off abx
  • No improvement after 72 hr → continue parenteral abx, review culture, imaging, drain obstruction or abscess

Indications for Imaging in Pyelonephritis

• Diabetes mellitus
• Poor response to treatment (72 hr)
• Hx of stones
• Hx of GU surgery
• Risk factor for papillary necrosis
• Older man with febrile UTI + flank pain = complicated UTI → CT urogram + cystoscopy even after cure
  • Higher rate of strictures (urethral/ureteral), tumor, stones

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Emphysematous Pyelonephritis

• Caused by gas-forming pathogens
• Risk: DM, high tissue glucose level
• E. coli most common, then Klebsiella & Proteus
• Classic triad: fever, vomiting, flank pain
• Imaging hallmark → gas within the renal parenchyma
  • vs emphysematous pyelitis → gas confined to the collecting system → usually responds to antibiotics alone
• Emergency → fluid resuscitation + broad-spectrum antibiotics + system drainage + control blood glucose
• If patient condition doesn't improve → nephrectomy advised
  • Nephrectomy = definitive treatment when septic with extensive diffuse gas + destroyed parenchyma
  • Otherwise percutaneous drainage is now the definitive management
  • Before nephrectomy → relieve obstruction (present in < 25%) with nephrostomy or stent + nuclear renal scan to assess function of both kidneys

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Renal Abscess

• On CT → low-density fluid-filled mass with rim enhancement
• Treatment:
  • < 3 cm → IV abx, conservative
  • If no improvement, OR > 5 cm → percutaneous drainage
  • Immunocompromised (e.g., lung transplant recipient) → add CT-guided needle drainage to IV abx, even if < 3 cm
• Infected ADPKD cyst:
  • Fever + flank pain persisting after 1 week of abx despite sterile urine → suspect infected non-communicating cyst
  • Imaging → CT or MRI (ultrasound compromised in polycystic kidneys)
  • Ciprofloxacin → penetrates cysts at higher-than-serum levels → effective
  • Dominant infected cyst (thick, enhancing wall) unresponsive to abx → percutaneous drainage = treatment of choice
    • Adding antibiotics alone is insufficient; partial or simple nephrectomy not indicated

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Xanthogranulomatous Pyelonephritis (XGP)

• Definition: unilateral non-functioning kidney with obstructive uropathy, persistent bacteriuria
• Risk: women > men; diabetics at increased risk
• Imaging: contracted renal pelvis & dilated calyces with obstructing stone → "bear claw" sign
  • CT classic triad in 50–80%: unilateral renal enlargement + large pelvic calculus without pelvic dilatation + little or no function
  • CT often cannot distinguish XGP from RCC
• Pathology: lipid-laden macrophages
  • Histology confirms: sheets of foamy macrophages
• Investigation: UA & culture + CT + DMSA
• Treatment:
  • Patient with UTI → drain the system & abx
  • Patient free of UTI → nephrectomy
  • Non-functioning kidney → total nephrectomy (radical or simple)
    • Often mimics cancer preop & is a source of recurrent infection
    • Abx serve to stabilize the patient beforehand
• Organism: E. coli + Proteus
  • Most common: Proteus mirabilis → urease → struvite staghorn calculus → drives the stone, chronic obstruction & infection triad

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Malakoplakia

• Soft plaque, can affect bladder & kidney
  • Yellow-brown & granulomatous
• Cause unknown
  • Probably abnormal macrophage function in response to bacterial infection, most often E. coli UTI
• Women > men (4:1); cystoscopy → raised bladder lesions → biopsy
• Pathology: von Hansemann cells & Michaelis–Gutmann bodies
  • von Hansemann cells = large histiocytes
  • M–G bodies = basophilic lysosomal inclusions within them, concentrically laminated & calcific
• Treatment → long-term abx ± TURBT or nephrectomy
  • Abx with high intracellular levels for several months: sulfonamide (TMP-SMX) or fluoroquinolone
  • ± bethanechol or ascorbic acid → enhance phagolysosomal activity

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Pelvic Lipomatosis & Cystitis Glandularis

• CT: "pear-shaped" bladder → pelvic lipomatosis
• Benign deposition of mature unencapsulated fat in the pelvic retroperitoneal space
• More common in Black men; associated with obesity
• Cystitis glandularis in up to 40%

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Fournier Gangrene

• Gas-forming bacterial infection in diabetic patient
• Organisms: E. coli, Proteus, Klebsiella, Enterococcus, Candida
• Spreads along dartos, Colles & Scarpa, & Buck's fascia
• Orchiectomy never performed — testis has different (own) blood supply
• Management → 2 regimens:
  • Carbapenem + Clindamycin
  • Tazocin + Clindamycin
• Survival improved by: early recognition + aggressive surgical debridement + broad-spectrum abx
  • Hyperbaric oxygen → not shown to reduce mortality
  • Transfer to a tertiary center → only after initial stabilization (transfer may interrupt or delay care)
• Scrotal debridement: usually only skin + dartos
  • External spermatic, cremasteric & internal spermatic fasciae → embryologically distinct, own blood & nerve supply → rarely necrotic → spared
• After initial debridement (even if all scrotal skin removed) → wet-to-dry dressings
  • Thigh pouches for the spared testes & wound VAC → only once the wound stabilizes
  • No skin graft at initial debridement (active infection + catabolic state) → reconstruction once the patient is stable with a healthy wound base
• Debrided wound heals by secondary intention → wound contraction
  • Driven by the myofibroblast (fibroblast with contractile smooth-muscle actin) pulling the edges together
  • Same force → stricture recurrence after internal urethrotomy: contraction narrows the lumen before re-epithelialization is complete
• Perineal abscess drained → urine from the wound = urethrocutaneous fistula, most often from inflammatory urethral stricture
  • No urethral instrumentation (sepsis risk) → suprapubic cystostomy → delayed urethral reconstruction

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Interstitial Cystitis (IC)

• Defined as LUTS (similar to OAB) but must have pain or discomfort, also associated with either:
  • Hunner ulcer, OR
    • Now Hunner lesion (HL) — a circumscribed inflammatory bladder lesion; found in < 30% of IC/BPS; usually easily seen on office cystoscopy
    • Exam answer: HL in about 15% of IC
    • HL patients → higher mean age, otherwise similar presentation; more likely to respond to bladder-centric therapy (e.g., lesion fulguration)
  • Glomerulations (cystoscopy → fill bladder to 60–100, should see diffuse glomerulation)
    • Nonspecific → no significance in an asymptomatic patient
    • Also seen after radiation, chemotherapy or toxic chemicals, in bladder carcinoma, and in bladders left unfilled (dialysis, urinary diversion)
  • Exam answer: pain, pressure or discomfort related to the bladder is the essential component; urgency, frequency, glomerulations and Hunner lesions are often associated but not required
• vs OAB → OAB urgency characteristically lacks pain; urgency driven by pain = bladder pain syndrome (BPS)
  • BPS distinguishers:
    • Painful symptoms
    • Pain rising steadily with filling
    • More consistent voided volumes
    • Preserved ability to defer voiding
  • Suprapubic pain on filling + frequency, urgency & nocturia
    • No response to antibiotics (argues against infection) and only minimal benefit from an antimuscarinic (pain, not detrusor overactivity) → BPS
• Exclusion criteria (the following exclude IC):
  • Bladder capacity > 350 mL
  • Duration < 9 months
  • Absence of nocturia
    • Absence of nocturia excludes because IC pain & urgency are driven by bladder filling, which continues overnight
  • These are the NIDDK research (not clinical) criteria
  • Also excluded: < 8 daytime voids; the > 350 mL is awake cystometric capacity
• People with IC often also have fibromyalgia
• Evaluation: Hx & PE + UA, cytology & symptoms, voiding diary & Score (cystoscopy & urodynamics optional)
  • Cystoscopy + low-pressure hydrodistention under anesthesia → most useful test for prognosis & therapy
    • Main value = finding a Hunner lesion → excellent response to resection or fulguration
  • Urodynamics → not indicated in uncomplicated IC/BPS (2022 AUA)
    • Mainly excludes other bladder dysfunction (failed empirical treatment, incontinence, high PVR)
    • Cystometry: ↓ capacity + hypersensitivity, pain on filling that reproduces symptoms, no detrusor overactivity
    • Compliance normal — hypersensitivity stops filling before noncompliance
• Diagnosis by exclusion
  • Histopathology → mainly to rule out other diseases
    • No pathognomonic finding
    • Cannot predict prognosis or, alone, guide treatment
  • IC-like symptoms + gross hematuria + severe bladder wall inflammation → take a recreational drug history:
    • Ketamine cystitis mimics IC/BPS and often inflames the upper tract too

IC Management (stepwise)

• 1st line — stress management, patient education, behavioral modification
• 2nd line — physiotherapy, amitriptyline, cimetidine, hydroxyzine, intravesical therapy (DMSO, heparin, lidocaine)
  • Oral pentosan polysulfate — slowly restores the urothelial GAG layer (only 3–6% of dose reaches urine) → allow a 6-month trial before calling it ineffective
• 3rd line — hydrodistension, fulguration of Hunner lesion
  • After hydrodistension: 30–50% short-term relief; about 30% brief flare; capacity under anesthesia < 200 mL = poor prognosis
  • Exam answer: focal Hunner lesion on cystoscopy + normal cytology → next step = biopsy + fulguration; AUA alternatives → laser or triamcinolone injected into the lesion
    • Fulguration / laser → complete relief in slightly > 50% + > 50% improvement in another 25%; about one-third of responders later recur
• 4th line — Botox injection
  • Sacral neuromodulation — commonly used for IC symptoms with benefit, but IC is not an approved indication (approved: urgency, frequency, urgency incontinence, idiopathic nonobstructive retention)
• 5th line — cyclosporine
• 6th line — urinary diversion

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Radiation (Hemorrhagic) Cystitis

• Transfusion-requiring bleeding after failed silver nitrate or 1% alum → 1–2% formalin instillation
  • Highly irritating → needs general anesthesia
  • Before instilling: cystogram (exclude vesicoureteral reflux) + cystoscopy (exclude a bladder lesion)
• Internal iliac embolization → reserved for formalin failure, or intractable bleeding with a nonfunctional bladder

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Prostatitis

Classification System

• Cat 3A → no uropathogenic bacteria
  • Excess leukocytes also counted in EPS → usually > 5–10 WBC/HPF in EPS or VB3 (or both)
• Cat 3B → pain + sterile cultures + no significant leukocytes
  • No validated cutoff → consensus upper normal in EPS = 5 WBC/HPF
• Leukocytes = weak classifier → counts fluctuate over time & with ejaculation frequency
  • Histologic inflammation in up to 44% of autopsy prostates from men never diagnosed with prostatitis

3-Glass Test (EPS & VB3 to differentiate)

• Four-glass test → no longer routinely used for suspected chronic bacterial prostatitis
• Urethral discharge → gonorrhea & chlamydia amplification testing (NAAT)

Acute Bacterial Prostatitis

• Fever, LUTS, tender boggy prostate
• Most common organism: E. coli → Don't do PR (DRE)
  • After lower urinary tract manipulation → E. coli still most common, but Pseudomonas far more common than in spontaneous or post-transrectal-biopsy cases
• Avoid prostatic massage & prostate biopsy in untreated bacterial prostatitis or prostatic abscess → can precipitate bacteremia & sepsis
• Duration of abx ≈ 4–6 weeks

Chronic Bacterial Prostatitis

• Seminal fluid → elevated LDH-5:LDH-1 ratio (LDH isoenzymes) + increased immunoglobulins
  • Antigen-specific IgA & IgG in prostatic fluid & seminal plasma
• Prostatic fluid is alkaline → favors concentration of zwitterionic fluoroquinolones within the gland

Chronic Pelvic Pain Syndrome (CPPS)

• Cat 3 = pain without bacteria → most often perineal, suprapubic & penile; pain during / after ejaculation among the most bothersome → chronic after 3 months
• History & PE (pelvic floor + DRE) & UA + culture
  • All mandatory
• Recommended tests: sexual Hx, 2-glass test, cytology, PVR + flow
  • Also NIH-CPSI + sexual function questionnaire
  • Painful ejaculation + frequency + suprapubic pain → suggests CP/CPPS
  • Uroflowmetry = recommended noninvasive screen for mimicking voiding dysfunction / obstruction
  • Invasive tests → not routine
• Management → Cipro (4 wk) + Tamsulosin (6 wk) + NSAIDs (2 wk)
  • Meta-analyses → best response with antibiotics + alpha-blockers combined
• CPPS associated with IBS
  • IBS = most common overlapping pain condition → ask about constipation, diarrhea & pelvic pain related to bowel movements → gastroenterology referral if indicated

Prostatic Abscess

• CT → localizes the abscess for operative planning + shows spread beyond the prostate
  • Rare abscess extending outside the prostate → may need open surgery
• < 2 cm → antibiotics
  • Exam answer: < 1–2 cm → initial IV antibiotics; antibiotics alone succeeded in cavities < 1 cm
• > 2 cm → drainage (percutaneous or deroofing)
  • Larger lesions or not responding to antibiotics → percutaneous aspiration or transurethral unroofing
  • 4.4 mL (≈ 2 cm) abscess → TRUS-guided aspiration (exam answer) → aspirate allows culture-directed therapy
  • Too large to drain percutaneously (e.g. 4 × 4 cm) or failed percutaneous drainage → TURP unroofing
    • Intraoperative US helps localize the cavity
• Seminal vesicle abscess → endoscopic unroofing by deep transurethral resection just distal to the bladder neck at 5 or 7 o'clock
  • CT-guided aspiration + drain → becoming the preferred least-traumatic option

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Epididymitis

• STD suspected (< 35 yr) → Ceftriaxone (250–500 mg IM) + Doxycycline (100 mg PO BID × 10 days)
  • Sexually active men < 35 → C. trachomatis or N. gonorrhoeae
  • Exam answer: single-dose ceftriaxone + doxycycline 100 mg BID × 10–14 days, started empirically before lab results
• Enteric suspected (> 35 yr) → Ceftriaxone (250–500 mg IM) + Levofloxacin (500 mg PO OD × 10 days)
  • Prepubertal boys and men > 35 → uropathogens, chiefly E. coli

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Chronic Scrotal Content Pain

• Primary scrotal pain syndrome → chronic scrotal pain with normal exam + ultrasound, no proven infection or local pathology
  • First → NSAIDs + scrotal support/elevation + reassurance
  • Chronic pelvic pain ladder → conservative + simple analgesia → neuropathic pain meds → nerve blocks + neuromodulation → surgery last
• Trifecta nerve complex → the 3 spermatic cord nerve complexes below
  • Main pain contributors in chronic orchialgia
  • Anatomic basis for relief after microsurgical cord denervation

• Spermatic cord block → selects candidates for denervation; degree of relief correlates with relief after surgery
• Microsurgical denervation of the spermatic cord (MDSC) → 81.6% pain-free at 2 yr
  • Goal → transect all genitofemoral nerve branches
  • Preserve vas deferens, vasal vessels, testicular artery, lymphatics (sparing lymphatics → avoids hydrocele)
  • Divide the cremasteric muscle fibers (densest innervation), spare the cremasteric arteries
  • Scrotal approach → also transect the posterior periarterial tissue / cord lipoma (easily left behind) → better pain control
  • Targeted MDSC → spares the inner spermatic sheath
    • Ligates only 5–10% of the cord (protects testicular + vasal arteries) + biowrap vs scarring/neuroma

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Sexually Transmitted Infections

Vaginitis

• Bacterial vaginosis → Gardnerella vaginalis + anaerobes overgrow and replace lactobacilli → discharge + odor but no itching or soreness
  • Discharge (exam answer): malodorous gray-yellow; +ve whiff test, vaginal pH > 5
  • Alternatives → metronidazole gel intravaginally OD × 5 days, or clindamycin cream × 7 days
  • Recurrence → persistent Gardnerella / Atopobium vaginae biofilm → suppressive metronidazole gel
• Trichomonas → frequency, urgency, dysuria + profuse discharge; microscopy → motile flagellated organism
  • Urinary symptoms from urethral involvement, not cystitis
  • Alternative → tinidazole 2 g PO single dose; treat the partner (unlike BV)

Chlamydia & N. gonorrhoeae

• Chlamydia → organism not visualized under microscope
  • Obligate intracellular → mucopurulent discharge with abundant neutrophils but no intracellular Gram −ve diplococci → non-gonococcal urethritis, most often C. trachomatis
• N. gonorrhoeae → Gram −ve diplococci
• Non-gonococcal urethritis → C. trachomatis 15–40%, M. genitalium 15–25%
  • Complications in men → epididymitis, orchitis, prostatitis, reactive arthritis
  • Major future risk → PID, tubal scarring, infertility in the often-asymptomatic female partner → treat partners

Approach to Non-Ulcer STDs (Urethritis)

• Hx & PE + UA & culture
• Gram stain of urethral secretion
• NAAT by urethral swab or urine
  • NAAT for N. gonorrhoeae, C. trachomatis + M. genitalium = test of choice; first-catch urine non-inferior to urethral swab
• Screen for syphilis + HIV + chlamydia in gonorrhea +ve patients

Management Algorithm (Urethritis)

• A. Treat initially for both N. gonorrhoeae + chlamydia
• B. Ceftriaxone (250–500 mg IM) to cover N.G. + Azithromycin (1 g PO once) or Doxycycline (100 mg BID × 7 days) for chlamydia
  • Doxycycline = first line for chlamydia; pregnancy → doxycycline contraindicated → oral azithromycin (safe)
  • Azithromycin → 1 g once only if M. genitalium excluded; otherwise 1 g day 1 → 500 mg daily days 2–4; follow-up cultures
• C. Symptoms persist even after completion of therapy
• D. Escalation:
  • Azithromycin used before → give Moxifloxacin 400 mg PO OD × 7 days
    • Relapse after single-dose azithromycin + ceftriaxone with −ve urethral culture → macrolide-resistant M. genitalium (EAU → moxifloxacin as above)
  • Doxycycline used before → give Azithromycin
    • Full doxycycline course failed → resistant Ureaplasma urealyticum (usually responds to azithromycin); relapse may be reinfection → retreat patient + all partners
  • Sex with woman in highly prevalent area → Metronidazole 2 g PO
• Mycoplasma genitalium:
  • Not grown on routine urethral culture → NAAT required
  • Macrolide resistance → 44–90% of US isolates
    • Single-dose azithromycin 1 g inadequate + selects 23S rRNA resistance mutations
    • Resistance-guided therapy → cure > 90%
  • CDC (no resistance testing) → NAAT +ve → doxycycline 100 mg BID × 7 days → then moxifloxacin 400 mg OD × 7 days
  • Moxifloxacin fails / contraindicated → sitafloxacin 100 mg BID × 7 days
• Treat the partner also
• Reiter syndrome → uveitis, arthritis, urethritis — associated with chlamydia (HLA-B27)

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Genital Ulcer Disease

• Genital herpes → most common cause of genital ulceration; the only vesicular GUD
  • First episode (exam answer): oral acyclovir, valacyclovir or famciclovir × 7–10 days, started before lab confirmation; IV acyclovir only for neurological complications, no oral intake, or widespread disease
  • Treatment controls the active episode (fewer symptoms + new lesions) → cannot eradicate latent virus in the sensory ganglia
  • Suppressive (continuous daily) → acyclovir 400 mg BID, or valacyclovir 500 mg or 1 g OD → fewer recurrences + less HSV-2 transmission to partners
  • Suppressive ↓ recurrence frequency; episodic ↓ lesion duration; recurrences less frequent with HSV-1 than HSV-2
• Syphilis
  • Primary → penile ulcer + spirochetes on dark-field → benzathine penicillin G 2.4 million units IM single dose, without waiting for serology
  • Secondary → 3–5 months after infection
    • Non-pruritic maculopapular rash on palms and soles
    • Diagnose by non-treponemal serology, confirm with treponemal test
    • Condylomata lata → highly infectious, moist, gray-white wart-like genital/anal plaques (not the HPV-driven condylomata acuminata)
  • Penicillin allergy → doxycycline 100 mg PO BID × 14 days (primary, secondary, early latent); late latent / unknown duration → 4 weeks
  • Pregnancy + penicillin allergy → desensitize, then benzathine penicillin G (only regimen proven to treat the fetus + prevent congenital syphilis)
  • Jarisch-Herxheimer reaction → fever, headache, myalgia within 24 h of treatment; from treponeme killing, not allergy → NSAIDs
• LGV (C. trachomatis L serovars) →
  • Tender, matted, typically unilateral inguinal nodes, purple adherent skin, fluctuant + indurated areas
  • Genital papule usually healed by presentation
  • Fluctuant bubo → aspirate, don't incise (avoids chronic sinus)
• Chancroid (H. ducreyi on culture) → men 3× women; unilateral tender inguinal nodes that suppurate + fistulize
  • First line → azithromycin 1 g PO single dose or ceftriaxone 250 mg IM single dose; ciprofloxacin = secondary
  • Re-examine in 5–7 days; treat sexual partners within 2 weeks

STD Testing

• Herpes → PCR + Tzanck smear
  • Exam answer: lesion swab NAAT/PCR preferred (intermittent shedding → culture falsely −ve) or viral/cell culture; Tzanck = non-specific + insensitive
  • Multiple vesicles on an erythematous base → swab lesion + type-specific serology to identify HSV type
• Chancroid → PCR + culture
• Lymphogranuloma → chlamydia culture + serology
  • Sample → lesion swab or bubo aspiration
• Syphilis → ① screen by VDRL, RPR ② confirm by FTA
  • −ve RPR doesn't exclude primary syphilis (lacks sensitivity) → painless glans ulcer: confirm with treponemal test (FTA-ABS or TPPA) before benzathine penicillin G
  • Treatment response → nontreponemal test (RPR or VDRL); significant = fourfold titer change = two dilutions (e.g. 1:16 → 1:4)
• All patients +ve with syphilis → screen for other STDs like HIV

Genital Warts (HPV / Condyloma)

• Condyloma acuminatum → cauliflower-shaped lesions; histology → koilocytes (squamous cells with a clear halo around a shrunken nucleus)
• HPV 6 + 11 (non-oncogenic) → ~90% of anogenital warts → cauliflower meatal wart = most likely HPV 6; HPV 16 + 18 = oncogenic
• Buschke-Löwenstein tumor (verrucous carcinoma) → main differential for a large condyloma
  • Also HPV 6/11 but invades locally, whereas condylomata stay superficial whatever their size
• Urethral warts → hematuria, dysuria, voiding difficulty → meatal condyloma: check proximal extent (intraurethral disease changes treatment + follow-up)
  • Extensive intraurethral → intraurethral 5-FU cream = initial treatment of choice; other option → holmium laser ablation
  • Podophyllin, imiquimod → not approved for internal use (tissue toxicity)
  • Cryotherapy → can't reach the proximal urethra
  • CO2 laser → absorbed by water → can't be used through a cystoscope

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HIV & Urology

Malignancy

• AIDS-defining cancers (3) → Kaposi sarcoma, non-Hodgkin lymphoma, invasive cervical cancer
• Increased in HIV → testis, kidney & penile cancer + Kaposi sarcoma
• Not increased → prostate cancer (RR no different or even lower — 0.70)
• Testicular germ cell tumor (esp. seminoma) → GU cancer most strongly linked to HIV
  • Non-AIDS-defining; 2- to 5-fold excess that persists despite antiretrovirals
  • Preserved CD4 + controlled viral load → standard-dose treatment (orchiectomy, BEP where indicated)
    • Dose reduction for serostatus alone worsens outcomes
• Intravesical BCG → use cautiously in HIV+ — efficacy depends on a functioning immune system

Kaposi Sarcoma

• Epidemic (AIDS-related) KS → HHV-8 (KSHV) in > 90%
• Painless, non-tender red scrotal lesion + HHV-8 in a transplant recipient → Kaposi sarcoma
  • Genital involvement typical in transplant & AIDS patients — classic KS → lower legs
• Transplant-related KS → reduce immunosuppression or switch calcineurin inhibitor → mTOR inhibitor → may clear the disease with no other treatment

Testis & Epididymis

• Testicular atrophy → most common intrascrotal pathology in HIV/AIDS
  • Causes:
    • Endocrine imbalance
    • Repeated fevers
    • Malnutrition
    • Testicular infection
    • Therapy toxicity
    • Direct HIV cytotoxicity to germ & Sertoli cells
• Testosterone falls as HIV disease progresses → check HIV+ men for hypogonadism
• All patients with epididymitis → screen for HIV
• HIV+ man with epididymitis → urethral Gram stain or urine PCR + empirical therapy, plus:
  • Syphilis serology — in the US, syphilis predominantly affects HIV+ patients
  • Hepatitis B & C testing

Needlestick Exposure & PEP

• Single exposure to HIV+ blood → transmission ~0.3% percutaneous · ~0.09% mucosal
• First aid → wash with soap & water; no squeezing, no bleach or antiseptic
• ↑ Seroconversion risk after needlestick:
  • Deep injury
  • Visible blood on the device
  • Device previously placed in an artery or vein
  • Death of the source patient within 2 months
• PEP → start as soon as possible, ideally within hours; 72 h = outer limit (not recommended beyond)
• Duration → 28 days (4 weeks) of combination antiretroviral therapy — standard for occupational & non-occupational exposures

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Genital Dermatoses

Lichen Sclerosus & Lichen Planus

• Lichen sclerosus (balanitis xerotica obliterans, BXO)
  • Histology → loss of rete pegs (epidermal atrophy) + basal cell vacuolation, dermal edema, collagen homogenization
  • Linked to penile SCC (esp. non-HPV types) → biopsy to confirm & exclude cancer
  • Late stage (BXO) → urethral strictures
• Lichen planus (genital)
  • Fails ultrapotent topical steroid (clobetasol 0.05%) → topical calcineurin inhibitors (tacrolimus, pimecrolimus)
  • Systemic therapy → severe disease only
  • Not responding → biopsy / re-biopsy — SCC is in the differential & can arise in chronic genital disease

Fungal Rashes

• Azoles cover both dermatophytes & yeasts

Reactive Arthritis & Behçet Disease

• Reactive arthritis → urethritis, arthritis, ocular inflammation, oral ulcers, skin lesions
  • Strong HLA-B27 association; usually follows chlamydial / gonococcal urethritis or GI infection
  • Only ~1/3 show all features
  • Painless glans ulcer with grayish border + large-joint polyarthritis → balanitis circinata
  • Balanitis circinata → usually self-limited (weeks–months); low-potency topical corticosteroids
  • Matching plantar lesion → keratoderma blennorrhagicum
• Behçet disease → oral + genital aphthous ulcers + uveitis
  • Genital ulcers larger & more painful than oral
  • Recurrent / chronic epididymitis → recognized feature
  • Clinical diagnosis, no confirmatory test → 2014 International Criteria ≥ 4 points:
    • Ocular lesions, oral aphthosis, genital aphthosis (2 each)
    • Skin, CNS, vascular (1 each)
  • Suspected (oral + genital ulcers not responding to abx) → start corticosteroids early without waiting for tests + involve rheumatology in parallel
    • Ocular involvement (90%) → blindness

Premalignant & Benign Lesions

• Bowenoid papulosis → penile high-grade squamous intraepithelial lesion; sexually transmitted, usually HPV-16
  • ~1% progress to invasive cancer → conservative management acceptable in a young, reliable man
  • Female partners → ↑ cervical neoplasia → close follow-up with Pap smears
• Seborrheic keratosis → benign, waxy, tan-to-brown "stuck-on" papule of older adults; can arise on the scrotum
  • No treatment needed; removal → cryotherapy, curettage or shave excision
• Leukoplakia → proposed risk factor for female primary urethral carcinoma
  • Others:
    • Glandular metaplasia
    • Chronic irritation
    • Stricture
    • Recurrent UTIs
    • Caruncles
    • HPV
  • Female urethral diverticula → may also predispose to urethral carcinoma
    • 6–10% harbor a malignancy
    • Adenocarcinoma = main cancer within them

Ammoniacal Meatitis & Meatal Stenosis

• Meatal stenosis weeks after infant circumcision → ammoniacal meatitis:
  • Diaper irritation of the unprotected meatus → chronic meatitis → scars to a pinpoint meatus
• Presents → upward stream deviation, narrow high-velocity stream with straining, pain at voiding onset
• Diagnosis → clinical (bougie calibration); treatment → meatotomy or meatoplasty

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Genitourinary Tuberculosis (GU TB)

• Symptoms: vague — fever, malaise, storage symptoms, hematuria, & sterile pyuria
• Most affected GU organ: kidney
  • Of bladder, prostate, epididymis & ureter → epididymis is the first GU site seeded by hematogenous spread
• Ureteric stricture → most often distal ureter, at the vesicoureteric (ureterovesical) junction
  • Bacilli descending from the kidney dwell longest there, + contiguous spread from TB cystitis
• TB cystitis → starts near the ureteric orifices, affects the dome most; usually spares trigone & bladder neck
  • Scars after ~1 yr → thimble bladder (< 20 mL)
• Diagnosis → 3 consecutive early-morning urine samples with acid-fast stain & mycobacterial culture
  • Serial first-void AFB cultures on 3–5 consecutive days, cultured promptly → bacillary shedding is intermittent
  • Urine AFB culture = gold standard (80–90% sensitivity when done properly)
  • GeneXpert (83–95%) → adjunct only; culture still needed for drug susceptibility testing & to monitor treatment response
• Radiographic findings → pipe-stem ureter, thimble bladder
  • Thimble bladder (small, fibrosed, contracted) → the characteristic IVP finding; augmentation cystoplasty once capacity < ~100 mL
  • IVU also:
    • Moth-eaten calyces
    • Phantom calyx
    • Beaded / corkscrew ureter
    • Autonephrectomy
  • 10–15% have a normal IVU → CT & MRI have largely replaced it
• Treatment (newly diagnosed) → 6 months
  • 2 months isoniazid + rifampin (rifampicin) + pyrazinamide + ethambutol → 4 months isoniazid + rifampin
  • Streptomycin → second-line, reserved for MDR TB
  • Renal failure → streptomycin & ethambutol contraindicated (depend on renal clearance)
  • Blurred vision → ethambutol's dose-dependent retrobulbar optic neuritis → stop ethambutol
    • Monitor visual acuity & red-green color vision while on it

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Parasitic Infections

Schistosomiasis (S. haematobium)

• Most common presentation → painless, recurrent hematuria (often + dysuria or frequency)
  • Begins ~8–12 weeks after infection, when eggs reach the bladder wall
• Diagnosis → terminal-spined eggs in urine = gold standard for active urogenital schistosomiasis
• Treatment → praziquantel (only WHO-recommended drug) → trial it before elective surgery in most cases
  • Dose → 20 mg/kg PO × 2, 6–8 h apart, same day (or 40 mg/kg single dose)
  • Efficacy 60–90% (egg reduction & cure rate)
• Chronic infection → bladder SCC — sustained inflammatory irritation → squamous metaplasia → malignant transformation

Filariasis & Chyluria (Wuchereria bancrofti)

• Patient from endemic area (e.g. Africa, India) + painless milky urine → chyluria from lymphatic filariasis (usually W. bancrofti)
  • Noninflammatory lymphourinary fistula → no dysuria or LUTS; typically worse after fatty meals
  • ± one-sided leg lymphedema
  • Heavy fat & protein loss → malnutrition
• Diagnosis → Giemsa-stained blood smear timed to nocturnal periodicity (peak microfilaremia ~midnight)
  • Often need circulating W. bancrofti antigen testing (ELISA or card test)
• Treatment → diethylcarbamazine (DEC) 2 mg/kg TID = treatment of choice for active disease
  • 1-day course usually matches 12 days
  • Kills microfilariae; only modest effect on adult worms
  • Patient from West / Central Africa → exclude onchocerciasis & Loa loa before DEC
• Established genital elephantiasis → not reversed by antiparasitic therapy → surgical reconstruction

Echinococcosis (Renal Hydatid Cyst)

• Mainstay → surgical removal of the cyst without rupture → ↓ seeding, antigen reaction & recurrence
• Cyst ruptures or needs marsupialization → aspirate its contents + fill with a scolicidal agent