NC.com

UTI Evaluation

Presenting symptoms

• Common: frequency, urgency, dysuria, suprapubic pain, fever
• Hematuria: can occur with UTI, check UA
• Pneumaturia/fecaluria: high suspicion for fistula
• Differential: bladder pain syndrome, STI, VUR, vaginitis/urethritis

Collecting the Sample

• Obtain clean catch (0 squamous cells is best sample)
• If tube (foley/PCN) present, consider exchanging (if possible) prior to collecting sample
• If ostomy, catheterize stoma for collection
• Do not collect from bag

Lab Findings

• Leukocyte esterase: sensitive but not specific for UTI
• Nitrites: produced by Enterobacteriaceae, also seen with pyridium
• Cloudy urine: pyuria or precipitated phosphate crystals in alkaline/concentrated urine

Defining Asymptomatic Bacteruria

• Bacteria in urine in the absence of any symptoms
• 1-5% healthy young women, 20% women older than 80
• 23-89% patients using CIC vs 100% patients with longterm catheter usage
• DO NOT TREAT even if diabetic, SCI, foreign body in GU tract
• Do not screen and do not treat prior to non-urologic surgery
• Only treat if pregnant or undergoing GU instrumentation

Spinal Cord Injury Patients

• Do not screen or treat asymptomatic bacteruria in patients with SCI and indwelling catheters
• Antibiotic prophylaxis and irrigation have not been shown to decrease bacteruria

Oral Antibiotics for Outpatient UTIs

Antibiotic	Normal Dosing	Side Effects	Tips
Nitrofurantoin (Macrobid)	100mg BID	GI effects Peripheral neuropathy Hemolysis if G6PD Pulmonary hypersensitivity reaction (rare)	Only works well for GU infections (not tissue) Don't give if GFR < 50 (inadequte excretion) Caution in elderly patients Do not take with quinolones, Mg, or probenecid
Trimethoprim-Sulfamethoxazole (Bactrim)	Double-Strength (800/160mg) BID	Rashes GI effects Hyperkalemia Stevens Johnson syndrome (rare)	Avoid in pregnancy Can exacerbate effects of warfarin
Fosfomycin	3g sachet x1	Headache GI effects Vaginitis	Not used frequently in US due to cost ($70-90)
Ciprofloxacin (Cipro)	500mg BID	GI effects, dizziness, photosensitivity CNS effects Tendon rupture	Avoid in children or pregnancy Decreased oral absorption with iron, zinc, or antacid (separate by 2hrs) Can lower seizure threshold
Levofloxacin (Levaquin)	250mg BID or 750mg daily
Cefuroxime		Diarrhea Rash Elevated LFTs	Do not use if patient has prior immediate hypersensitivity to penicillins Use with caution if delayed hypersensitivity to penicillins
Cefoxitin
Ampicillin (w/ Sulbactam)	875/125mg BID	Hypersensitivity rash Diarrhea	Rash more likely when viral disease present

Antibiotic Coverage

	Streptococcus	MRSA	Staph saprophyticus	Enterococcus	E coli	Other GNRs	Pseudomonas	Anaerobes
Macrobid Urinary pathogens only	No	No	Yes	Yes	Yes	Yes	No	No
Bactrim	Yes	Yes	Yes	No	Yes	Yes	No	Yes
Levaquin/Cipro	No	No	No	No	Yes	Yes	Yes	No
Zosyn/Augmentin	Yes	No	Yes	Yes	Yes	Yes	No	Yes
1st gen Ceph Cefazolin/Cephalexin	Yes	No	Yes	Yes	Yes	Yes	No	No
2nd gen Ceph Cefuroxime/Cefoxitin	Yes	No	Yes	Yes	Yes	Yes	No	Yes
3rd gen Ceph Ceftriaxone/Cefpodoxime	Yes	No	Yes	Yes	Yes	Yes	Yes (Ceftazidime only)	No
4th gen Ceph Cefepime	No	No	No	No	Yes	Yes	Yes	No
5th gen Ceph Ceftaroline	No	Yes	No	No	Yes	Yes	No	No
Carbapenems	Yes	Yes	Yes	No	Yes	Yes	Yes	No
Aminoglycosides	No	No	No	No	Yes	Yes	Yes	No
Vancomycin	Yes	Yes	Yes	Yes (except VRE)	No	No	No	No
Linezolid	Yes	Yes	Yes	Yes (including VRE)	No	No	No	No
Fosfomycin	Yes	Yes	Yes	Yes	Yes	Yes	Yes	No

Cystitis

Tips for diagnosis/management

• Dysuria is most specific symptom, but differentiate from vaginitis
• If only symptoms are foul-smelling or cloudy urine, encourage hydration and reassess
• Dysuria + frequency + no vaginal irritation - UTI probability > 90%
• Repeat UCx is not necessary if symptoms resolve with treatment

Factors indicating complicated cystitis

• Anatomic: cystocele, fistula, diverticulum
• Obstruction: BOO, UPJO, stricture
• Iatrogenic: hospital-acquired infection, recent GU surgery, indwelling catheter
• Functional: NGB, PFD, VUR, elevated PVR, incontinence
• Other factors: pregnancy, stones, DM, immunosuppresion

Emphysematous cystitis

• Seen in patients w/ complicating factors: DM, age, BOO, NGB
• CT (required for diagnosis) shows air within bladder wall (submucosal)
• Treatment: abx, catheterization, and DM management

Renal Infections

Acute Pyelonephritis

• Acute pyelo is a clinical diagnosis: fever + flank pain, lower urinary symptoms may (not) be present
• DO NOT diagnose acute pyelo based on CT findings
• Obtain BCx if male, or female with systemic symptoms or with risk factors
• Imaging is not required, but can obtain renal US to assess for stones/hydro
• CT imaging warranted in patient with systemic symptoms or presumed complicated pyelo
• Uncomplicated patient can be treated outpatient with PO antibiotics
• Patients with persistent fever and symptoms > 72hrs despite abx, assess with CT imaging

Emphysematous Pyelonephritis

• Gas-forming infection usually seen with DM + obstruction
• Mortality rate 19-43%
• Most present with fever + vomiting + flank pain
• Diagnosis made by demonstrating air in renal parenchyma
• Treat w/ PCN placement - nephrectomy if extensive gas w/ renal destruction

Acute Focal/Multifocal Bacterial Nephritis

• Presents similar to pyelonephritis but with more severe symptoms
• Diagnosed via CT with contrast, area of decreased enhancement
• Treat with IV abx for 7+ days, then 7 days PO abx

Renal Abscess

• Can present with variety of symptoms - fever, chills, abd/flank pain, weight loss, cystitis
• If < 3-5cm (depending on reference), treat with abx and observe
• If > 3-5cm, clinically unstable, or immunocompromised, drain percutaneously

Infected Hydronephrosis +/- Pyonephrosis

• Bacterial infection in a hydronephrotic kidney +/- parenchymal destruction
• Imaging shows hydronephrosis with abnormal fluid, possible fat stranding
• Treat with either stent or PCN

Perinephric abscess

• Abscess extending through renal capsule but contained within Gerota's
• Caused by abscess rupture, extravasation of infected urine, or spread from another source
• Psoas abscess: limping, flexion + external rotation of hip
• Mortality rate 12-50%
• If < 3cm, treat with abx only, otherwise drain abscess
• Differentiate from pyelonephritis: usually have symptoms > 5 days, and repain febrile for longer than 4 days

Chronic pyelonephritis

• Rare cause of renal failure in patients without underlying abnormalities
• Blunted/dilated calyces and cortical scars seen on imaging

Xanthogranulomatous pyelonephritis (XGP kidney)

• Specific pathology due to accumulation of lipid-filled macrophages, requires pathology for diagnosis - may be mistaken for ccRCC
• Presents with flank pain, fever, persistent bacteruria
• CT triad: unilateral enlargement + little/no function + large stone in renal pelvis, present in 50-80% patients
• Usually treated with nephrectomy (may be difficult), although stones can be treated with PCNL

Sexually transmitted and other genital infections

Male Urethritis

Disease	Diagnosis	Treatment	Follow-Up
Gonorrhea	Urine NAAT	Ceftriaxone 250mg IM x1 + Azithromycin 1g PO x1 Substitute gemifloxacin 320mg PO x1 or gentamicin 240mg IM x1 if cephalosporins contraindicated	Abstain from sexual contact x7 days Repeat test in 3-4mo Test prior partners within past 60 days
Chlamydia		Azithromycin 1g PO x1 Doxycycline 100mg PO BID x7 days Erythromycin 500mg PO QID x7 days Levofloxacin 500mg PO daily x7 days Ofloxacin 300mg PO BID x7 days
Mycoplasma	Difficult to diagnosis Suspect if persistent/recurrent urethritis	Azithromycin 1g PO If fails, moxifloxacin 400mg daily x7-14 days	Abstain from sex until symptoms resolve and treatment completed test prior partners within past 60 days

Genital Ulcers

Disease	# Ulcers	Painful?	Lymphadenopathy?	Diagnosis	Treatment
Syphilis Treponema pallidum	Single	No	Regional	Nontreponemal (sensitive): VDRL, RPR Treponemal (specific): FTA-ABS, EIAs	Benzathine penicillin G 2.4 million U IM x1 Doxycycline 100mg PO BID x14 days Tetracycline 500mg PO QID x14 days Other treatments for tertiary syphilis
Herpes HSV	Multiple	Yes	Painful bilateral	Cell culture + PCR (swab ulcer base)	Acyclovir 400mg PO TID x7-10 days Acyclovir 200mg PO x5 x7-10 days Valacyclovir 1g PO BID x7-10 days Famciclovir 250mg PO TID x7-10 days Other regimens for recurrent episodes
Chancroid Haemophilus ducreyi	Multiple, raw	Yes	Unilateral and painful (50%) may become fluctuant and rupture	1+ painful genital ulcers + typical chancroid appearance + negative syphilis and HSV tests	Azithromycin 1g PO x1 Ceftriaxone 250mg IM x1 Ciprofloxacin 500mg PO BID x3 days Erythromycin 500mg PO TID x7 days
Granuloma inguinale Klebsiella granulomatosis	Multiple, friable	No	None	Send-out test	Azithromycin 1g PO qWeek 500mg PO qDay x3 weeks Consider biopsy if no resolution
Lymphgranuloma Venereum C. trachomatis serovars L1-3	Single	No	Painful and unilateral	NAAT available	Doxycycline 100mg PO BID x21 days Erythromycin 500mg PO QID x21 days
Molluscum contagiosum MCV	Multiple	No	No	Based on clinical picture	Observation Avoid auto-inoculation Local therapies

Human papillomavirus(HPV)

• Can cause warts and squamous cell cancer
• Biopsy indications: uncertain diagnosis, no response to standard therapy, worsening during therapy, immunocompromised, pigmented warts, indurated warts, affixed to underlying tissue, persistent ulceration or bleeding
• Patient-applied topical therapies: imiquimod cream 3.75% daily x16 weeks at bedtime, imiquimod cream 5% daily 3x weekly x16 weeks at bedtime, podofilox 0.5% solution/gel 0.5mL/day (max) BID x3 days (rest 4 days) x4 cycles (max), sinecatechins 15% ointment TID x16 weeks
• Physician-applied topical therapies: cryotherapy q1-2 weeks, direct excision, laser therapy, trichloroacetic acid/bichloroaceditc acid 80-90% (neutralize if severe pain with soap/water or NaBicarb)
• Topical treatments may weaken condoms and condoms may not protect partner from HPV exposure
• HPV vaccine available for ages 9-45

Human immunodeficiency virus

• Initially presents with nonspecific flulike symptoms x2-4 weeks, then may be latent for months-years
• Diagnosis via screening test should be confirmed with a separate test
• Circumcision reportedly reduces transmission risk by 50-60% (in high risk populations only)
• Postexposure prophylaxis should be given for non-occupational exposure within 72hrs
• Preexposure prophylaxis should be given to individuals at higher risk for transmission
• Increases risk for other STIs, skin infections, HPV, squamous cancer, GU infections, voiding dysfunction, erectile dysfunction
• Urologic manifestations: GU TB, hemorrhagic cystitis (BK, adeno, CMV), Kaposi sarcoma, testis cancer, RCC, nephropathy (HIVAN), retention, hypogonadism, indinavir stones

Fournier gangrene

• Gangrene of male genitalia, usually with underlying comorbidities/causes
• Spreads along tissue plans - Dartos fascia, Colles fascia, Scarpa fascia
• If suspected, perform immediate extensive debridement, SPT if urethral invovement, colostomy if colonic/rectal involvement
• Orchiectomy rarely required due to separate blood supply

Other genital infections

• Periurethral abscess: can spread through Buck fascia and cause extensive infection, treat with SPT drainage and debridement
• Pubic lice (Pediculosis pubis): can be seen in children without sexual contact, nits/lice usually visible, manage with permethrin 1% cream rinse or malathion 0.5% lotion, wash clothes/bedding in hot water or seal in a bag x3 days
• Scabies (Sarcoptes scabiei): rash/itching with serpiginous lines, manage with permethrin 5% cream or ivermectin 200ug/kg PO, wash clothes/bedding in hot water or seal in a bag x3 days

Vaginitis

Diagnosis	Discharge	pH	Microscopy	Symptoms	Treatment	Treat partner?
Normal discharge	White, thick, smooth	≤ 4.5	Lactobacilli	-	-	-
Candidiasis (C. albicans)	White, thick, curdlike		Mycelia	Itching, dysuria	Topical therapies Fluconazole 150mg PO x1 Persistent/recurrent infections may require alternate treatments for non-C. albicans	No
Trichomoniasis	Frothy, purulent	≥ 4.5	Trichomonads, WBC, amine odor	Vulvar erythema/edema	Metronidazole 2g PO x1 Tinidazole 2g PO x1	Yes
Bacterial vaginosis	Thin, white		Absent lactobacilli, clue cells, amine odor	Increased discharge, odor	Metronidazole 500mg PO BID x7 days Metronidazole gel 0.75% intravaginally daily x5 days Clindamycin 2% cream intravaginally QHS x7 days	No

Tuberculosis

Epidemiology

• 10 million active TB cases worldwide, < 10 thousand in US
• GU TB seen in 2-20% patients, more prevalent in non-Euro/Anglocentric countries
• 3rd most common TB manifestation after pleural and lymphatic

GU TB Spread

• Hematogenous: most common, most commonly to kidneys and epididymis
• Retrograde: may be secondary to BCG usage (0.9% total BCG usage)
• Continguous spread: TB can spread via adjacent organs and does not "respect" normal anatomic boundaries, can form fistulae
• Direct inoculation: extremely rare, can spread from infected persons or bodily fluids, patients can spread to new organs through their own infected fluids

Manifestations

• Constitutional: fever, weight loss, night sweats, malaise present in < 20%
• LUTS: up to 50% have dysuria only, 50% have frequency/urgency, 33% have hematuria/flank pain
• Kidney: seen in up to 80% GU TB, granulomas can develop into abscesses, chronic pylonephritis, papillary necrosis, cutaneous sinus tracts, may result in autonephrectomy (seen in 33% GU TB)
• Ureter: usually descending infection, granuloma formation leads to scarring/strictures, can lead to renal failure from obstruction
• Bladder: patchy cystitis, ulcerations, dome affected more than trigone, bladder may contract down to volumes 20-100mL (thimble bladder)
• Epididymis: second most common site, involved in 10-55% GU TB, bilateral infection in 34%, may appear swollen/hardened on exam, up to 50% have posterior scrotal sinus tract, can cause vas nodular scarring, can spread to testis and cause orchitis, 5% develop hydrocele
• Prostate: seen in 22-49% GU TB, can be peripheral/asymptomatic (if hematogenous spread) or prostatitis (if urinary spread), suspect in chronic prostatitis despite antibiotics
• Seminal vesicle: can cause infertility and may be presenting symptom of GU TB, may cause hematospermia and rarely abscesses
• Urethra: seen in 2-4.5% GU TB, can lead to urethroscrotal fistulae
• Penis: can develop inflamed papule/plaque (lupus vulgaris), may have palpable granulomas in cavernous bodies and urethra, can be rapidly necrosing with poor prognosis (orificial TB), can be penile glandular papules (papulonecrotic tuberculid)

Diagnosis

• Urinary AFB culture is gold standard, first morning void is most concentrated, collect 3-5 on consecutive days for best diagnosis, culture growth can take 3-6 weeks, may be able to detect colony growth at 10 days
• NAAT can detect within 1-2 days, but less sensitivte on non-pulmonary specimens
• Tissue biopsy demonstrates caseating granulomas, diagnostic in appropriate clinical context
• Screening tests (PPD, IGRA) do not differentiate between latent TB, active TB, or prior vaccination
• KUB: may show renal calcifications (present in > 50%), papillary necrosis, atrophic kidney with calcifications lining each renal lobe (pathognomonic for end-stage TB), calficiations elsewhere in GU tract
• CTU/IVP/MRU: demonstrates calyceal erosions (moth-eaten appearance), filling defects, phantom calyces (infundibular stenosis leads to failed contrast excretion), rigid ureter (pipestem), hydronephrosis, sharply angulated UPJ (Kerr's kink)
• Cystoscopy: findings mistaken for malignancy, biopsy recommended for diagnosis
• Check for HIV, HBV, HCV, and DM

First Line Therapies

Drug	Dosing	Side effects
Isoniazid	5mg/kg (300mg) daily 15mg/kg (900mg) 3x weekly	Hepatotoxicity Peripheral neuropathy
Rifampin	10mg/kg (600mg) daily 10mg/kg (600mg) 3x weekly	Hepatotoxicity Pruritis Flulike symptoms
Pyrazinamide (weight-based dosing)	1000-2000mg daily 1500-3000mg 3x weekly	Arthralgia Hepatotoxicity Pruritus/Rash GI Symptoms Hyperuricemia
Ethambutol (weight-based dosing)	800-1600mg daily 1200-2400mg 3x weekly	Decreased visual acuity Red/green color changes Optic neuritis

Treatment tips

• 6mo treatment total, 2mo with RIPE then 4mo with INH + rifampin
• Give Vitamin B6 with INH to decrease risk of neuropathy
• Use second-line therapies if TB are resistant or side effects develop from first-line therapies
• Check monthly LFTs, abstain from EtOH
• Second line drugs: streptomycin, capreomycin, amikacin, kanamycin, cycloserine, ethionamide, levofloxacin, moxifloxacin, paraASA, linezolid, bedaquiline

Surgical management

• Up to 55% with require some form of surgical therapy
• Obstruction: stent placement successful ~40% patients, 1+ PCNs may be needed if renal scarring prevents adequate drainage, fistula can develop after PCN removal
• Nephrectomy: may be necessary for resistant HTN, retroperitoneal approach may be needed due to severe scarring
• Ureteral obstruction: individualized approach, endoscopic management usually fails, may have lengthy strictures
• Bladder augment vs diversion: recommended for contracted poorly functional bladders

Parasitic GU infections

Schistosomiasis (Schistosoma haematobium)

• Repeat exposure required for clinical manifestations, otherwise short term exposure leads to adult worms dying within 3-5yrs and no parasitic reaccumulation
• Acute: rash, fever, headache, diarrhea, eosinophilia, urticaria
• Hematuria: considered sign of "male puberty" in some cultures, can cause anemia
• Eggs accumulate and calcify in GU tract, leading to decreased compliance and obstruction
• LUTS: bladder contraction can lead to volumes as low as 50mL with LUTS
• Hydroureter: may be segmental (downstream fibrosis without upstream hydronephrosis), tonic (thick-walled, impaired peristalsis, with complete upstream dilation), or atonic (thin walled, atrophic, upstream dilation)
• UTI: bacterial superinfections common
• Bladder cancer: squamous cell more common, may be synergistic with tobacco
• Female infection: fibrotic nodules in uterus, cervix, and GU tract, can lead to dyspareunia, infertility, and vaginal bleeding
• Lab diagnosis: eggs in urine/stool is gold standard, PCR is highly sensitive but less available, collect urine between 9AM-3PM (max shedding around noon) rectal biopsy preferred over bladder biopsy, can use ELISA
• Imaging: KUB may show calcified bladder, IVU shows hydronephrosis and obstructed ureters
• Praziquantel 20mg/kg x2 6-8hr apart on same day, can repeat if concern for recurrent/persistent infection, mild side effects
• Surgery: indicated for bladder hemorrhage, contracted bladders, persistent ureteral obstruction after medical therapy (can use balloon dilation)

Lymphatic filariasis (LF)

• Caused by Wuchereria bancrofti, Brugia malayi, and Brugia tiimori
• Acute infection: fever, enlarged LN, and lymphangitis, scrotal pain, and scrotal lymphatic drainage
• Hydrocele: can be large, thick fibrous tunica with cholesterol/calcium deposits
• Funiculoepididymitis: rarely causes orchitis or sterility, may be mistaken for testis cancer
• GU elephantiasis: almost always due to LF, usually in areas with poor medical care, skin thickening, can have bacterial superinfection
• Chyluria: due to damaged lymphatics, can lead to malnutrition
• Diagnosis: based on clinical picture and location/travel history, may be able to see microfilariae on blood smear, can use ELISA/PCR
• Medical treatment: diethylcarbamazine 2mg/kg PO TID x1 day for active infection, alternates include albendazole 400mg PO BID x3 weeks or ivermectin 150-400ug/kg PO x1 dose, can consider adding doxycycline 200mg/d PO x6 weeks to suppress microfilaremia
• Surgical treatment: rarely indicated, can consider hydrocele drainage or resection, consider lymphatic ligation, scrotal reconstruction

Other parasitic infections

• Onchocerciasis (Onchocerciasis volvulus): can cause scrotal elephantiasis, treat with ivermectin 150ug/kg PO x1, repeat q6-12mo until asymptomatic, can consider adding doxycycline 200mg/d PO x6 weeks to suppress microfilaremia
• Loaiasis (Loa loa): can cause hematuria/proteinuria (30%), rarely causes hydrocele and lymphadenitis, treat with diethylcarbamazine 2-3mg/kg PO TID 2-3 weeks, treatment in patients with high levels microfilaremia can cause encephalopathy
• Echinococcosis (Echinococcus granulosus): can cause painful renal cysts (2-3%), may have large cyst with calcified wall, manage with albendazole 400mg PO BID 1-6mo or surgical excision (cyst rupture can cause anaphylaxis)
• Enterobiasis (Enterobius vermicularis): commonly cause perianal pruritus, can spread through female GU tract and cause granulomas/adhesions, treat with albendazole 400mg PO or mebendazole 100mg PO x1
• Amebiasis (Entamoeba histolytica): can cause renal infection or perianal/genital ulcers, treat with tinidazole 2g PO QD x3-5d or metronidazole 750mg PO TID x10d, followed by paromomycin 8-12mg/kg PO TID x7 days or iodoqinol 650mg PO TID x20d

References

• AUA Core Curriculum
• Chang, A., B. Blackburn, and M. Hsieh. "Tuberculosis and Parasitic Infections of the Genitourinary Tract." Campbell-Walsh-Wein Urology. 12th ed. Elsevier (2020): 1129-1201.
• Cooper, K. L., G. M. Badalato, and M. P. Rutman. "Infections of the urinary tract." Campbell-Walsh-Wein Urology. 12th ed. Elsevier (2020): 1129-1201.
• McKiernan Borawski, K. "Sexually Transmitted Diseases." Campbell-Walsh-Wein Urology. 12th ed. Elsevier (2020): 1129-1201.