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UROGENITAL TRACT INFECTIONS - COMPLETE EXAM GUIDE

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LONG ANSWER QUESTIONS (LAQs)

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LAQ 1: Classify urinary tract infections. Describe the etiology, pathogenesis, clinical features, laboratory diagnosis, and treatment of uncomplicated UTI.

• Lower UTI - cystitis (bladder) and urethritis (urethra)
• Upper UTI - pyelonephritis (renal parenchyma and ureters)

• Community-acquired
• Hospital-acquired (nosocomial)

• Uncomplicated UTI - occurs in a structurally and functionally normal urinary tract (typically young women)
• Complicated UTI - associated with functional or anatomical abnormalities, renal impairment, indwelling catheters, immunosuppression, pregnancy, or diabetes

• Relapse - same organism within 2 weeks after treatment (indicates inadequate therapy or renal source)
• Reinfection - new organism or same organism >2 weeks after treatment

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• E. coli - the most common (>80% of cases); produces adhesins (pili/fimbriae), toxins, and iron-chelating siderophores
• Klebsiella spp.
• Proteus spp. (urease-positive; associated with struvite stones)
• Enterobacter spp.
• Staphylococcus saprophyticus - second most common in young sexually active women
• Corynebacterium urealyticum

• Enterococci
• Staphylococcus aureus
• Acinetobacter spp.
• Coagulase-negative staphylococci (CONS)
• Candida spp.
• Pseudomonas aeruginosa

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1. Ascending route - most common. Periurethral colonization → urethra → bladder → ureters → kidneys
2. Predisposing factors: short urethra in women (explains higher female incidence), sexual intercourse, use of spermicides/diaphragm, urinary catheters, urinary stasis, vesicoureteral reflux (VUR)
3. Virulence factors of E. coli:
   • Type 1 fimbriae (mannose-sensitive): bind uroepithelial cells
   • P-fimbriae (mannose-resistant, Pap): bind globoside receptor; critical for pyelonephritis
   • Hemolysin (HlyA): damages renal tubular cells
   • Aerobactin: iron chelation siderophore
   • K antigen (capsule): anti-phagocytic

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• Cystitis: dysuria, frequency, urgency, suprapubic discomfort, cloudy/foul-smelling urine, no fever
• Pyelonephritis: fever, chills, loin pain, costovertebral angle tenderness, nausea/vomiting, plus lower UTI symptoms
• Asymptomatic bacteriuria: significant bacteriuria with no symptoms (treatment indicated in pregnancy and pre-urological surgery)

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• Midstream clean-catch urine (MSU) - most common; patient voids initial stream, collects midstream
• Catheter specimen - higher quality; avoids urethral contaminants
• Suprapubic aspiration (SPA) - gold standard; any organism recovered is significant; rarely used due to invasiveness
• Bag urine - only for urinalysis in children, not acceptable for culture

• Leukocyte esterase - marker of pyuria (WBCs), sensitive but not specific for UTI
• Nitrite test - positive if gram-negative bacteria present (they reduce nitrate → nitrite); specific but less sensitive (requires ≥4 h of urine incubation in bladder)
• Combination positive = strong predictor of UTI

• Pyuria: >10 WBCs/mm³ (or >5 WBCs/high-power field)
• Bacteriuria: bacteria visible on unspun urine Gram stain

• ≥10⁵ CFU/mL = significant bacteriuria in MSU specimen (Kass, 1956)
• ≥10³ CFU/mL may be significant in symptomatic young women with uncomplicated cystitis
• ≥10² CFU/mL significant in catheter specimens
• Any growth in SPA = significant

• Blood agar (BAP) + MacConkey agar
• Incubated 24-48 hours at 37°C in 5% CO₂

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• Uncomplicated cystitis: oral nitrofurantoin (5 days), trimethoprim-sulfamethoxazole (3 days), or fosfomycin (single dose)
• Uncomplicated pyelonephritis: fluoroquinolones (7 days) or oral beta-lactams (10-14 days)
• Complicated UTI: based on culture/sensitivity; broader spectrum antibiotics
• Asymptomatic bacteriuria: treat only in pregnancy and pre-operative urological procedures
• Recurrent UTI: low-dose prophylaxis (nitrofurantoin or TMP-SMX)

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LAQ 2: Describe the microbiology, pathogenesis, clinical features, laboratory diagnosis, and treatment of Gonorrhea.

• Gram-negative diplococci (0.6-1.0 μm), arranged in pairs with adjacent sides flattened ("coffee bean" appearance)
• Strictly aerobic; oxidase positive, catalase positive
• Fastidious - growth requires: 35-37°C, humid atmosphere with 5-10% CO₂ supplementation, enriched media
• Acid produced from glucose by oxidation (not fermentation); differentiates from other Neisseria
• Humans are the ONLY natural host

• STI; highest incidence in 15-24 year age group
• ~555,608 cases/year in USA; estimated 78 million new cases worldwide annually
• Carriage can be asymptomatic in women (major reservoir)
• Higher risk of disseminated disease in patients with terminal complement component deficiencies (C5-C9)

1. Attachment to non-ciliated columnar epithelium of urethra, endocervix, rectum, pharynx, conjunctiva via pili and Opa proteins
2. Endocytosis - organism taken up in endosomes
3. Avoids phagolysosome fusion (Por proteins)
4. Transcytosis to subepithelial tissues → inflammation
5. LOS triggers intense neutrophilic response → purulent discharge

• Incubation: 2-5 days
• Urethritis with profuse purulent urethral discharge
• Dysuria, frequency
• Complications: epididymitis, prostatitis, urethral stricture

• Often asymptomatic
• Endocervicitis: mucopurulent cervical discharge
• Urethritis, Bartholin's gland abscess
• Complications: PID (pelvic inflammatory disease) → salpingitis → tubo-ovarian abscess → infertility, ectopic pregnancy

• 1-3% of patients with mucosal infection
• Triad: pustular rash with erythematous base on extremities + migratory polyarthritis + tenosynovitis
• Septic arthritis (most common form of infectious arthritis in sexually active young adults)

• Purulent ocular infection in neonate acquired at birth from infected birth canal
• Presents within 2-5 days of birth
• Can lead to corneal ulceration and blindness if untreated

1. Gram stain: Gram-negative intracellular diplococci within neutrophils
   • Sensitivity: 90-95% in symptomatic men; only 40-60% in women (not reliable for cervical specimens)
2. Culture:
   • Selective media: Modified Thayer Martin (MTM) agar or GC-Lect agar
   • Contains vancomycin, colistin, nystatin to inhibit normal flora
   • Incubate at 35-37°C in 5% CO₂ for 24-48h
   • Colonies: small, gray, translucent, oxidase positive
3. NAATs (Nucleic Acid Amplification Tests):
   • Most sensitive and specific
   • Can use urine, urethral, cervical, or vaginal swabs
   • Method of choice for most laboratories now
4. Identification: oxidase test + acid from glucose only (not maltose, lactose, or sucrose)

• Current treatment of choice: Ceftriaxone 500mg IM (single dose) - due to rising resistance to previous dual therapy
• Ophthalmia neonatorum prophylaxis: 1% silver nitrate or erythromycin eye drops at birth
• Ophthalmia neonatorum treatment: Ceftriaxone IV
• Treat sexual partners; co-treat for Chlamydia (common co-infection)

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LAQ 3: Write about Chlamydia trachomatis - biology, classification, clinical syndromes, diagnosis, and treatment.

• Small gram-negative (Gram stain NOT useful - too small)
• Obligate intracellular parasites - cannot synthesize ATP (energy parasites)
• Infect non-ciliated columnar, cuboidal, and transitional epithelial cells
• Have a unique biphasic life cycle:

• EB attaches to host cell → taken up into endosome (inclusion) → RB reorganization → binary fission of RBs → reorganization back to EBs → release by cell lysis or exocytosis
• Prevents phagosome-lysosome fusion (key intracellular survival mechanism)
• Lipopolysaccharide (LPS) antigen shared by all Chlamydia and Chlamydophila species
• Major outer membrane protein (MOMP) is species-specific

• Most common bacterial STI in the USA and worldwide
• Trachoma predominantly in North Africa, sub-Saharan Africa, Middle East, South Asia
• LGV highly prevalent in Africa, Asia, South America

• Men: Non-gonococcal urethritis (NGU) - dysuria, mucopurulent urethral discharge (milder than gonorrhea); epididymitis
• Women: Cervicitis (mucopurulent discharge), urethritis, endometritis, salpingitis, PID
• Both: Reactive arthritis (Reiter syndrome: urethritis + conjunctivitis + arthritis)

• Stage 1: Small painless papule/vesicle at inoculation site (heals in 1 week)
• Stage 2: Painful inguinal lymphadenopathy ("groove sign" - nodes above and below inguinal ligament separated by groove); bubo formation
• Stage 3: Genitoanorectal syndrome - proctitis, rectal stricture, elephantiasis of genitalia

• Inclusion conjunctivitis (5-12 days after birth; unlike gonococcal which is 2-5 days)
• Chlamydial pneumonia (6-12 weeks; staccato cough, no fever)

1. Culture on McCoy cells - highly specific, relatively insensitive (gold standard for medicolegal purposes)
2. NAATs - most sensitive and specific; test of choice; can use urine, urethral, cervical swabs
3. Direct Fluorescent Antibody (DFA) - detects EB directly in smears
4. ELISA - antigen detection; relatively insensitive
5. Serology (MIF - microimmunofluorescence): Useful for LGV and chlamydial pneumonia
6. Giemsa/iodine staining: Detects inclusions in conjunctival cells (historical, rarely used now)

• Uncomplicated genital/ocular infection: Azithromycin 1g single dose OR Doxycycline 100mg BD × 7 days
• LGV: Doxycycline 100mg BD × 21 days (prolonged)
• Neonatal conjunctivitis/pneumonia: Erythromycin syrup × 14 days
• Trachoma: Azithromycin single dose (SAFE strategy - WHO); tetracycline eye ointment

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SHORT ANSWER QUESTIONS (SAQs)

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SAQ 1: Significant bacteriuria - define and explain clinical significance.

• Coined by Kass (1956) for diagnosis of pyelonephritis
• Defined as ≥10⁵ CFU/mL (100,000 CFU/mL) of a single uropathogen in midstream clean-catch urine
• In symptomatic women with uncomplicated cystitis: ≥10³ CFU/mL may be significant
• In catheter specimens: ≥10² CFU/mL
• In suprapubic aspiration (SPA): any count is significant (specimen is from sterile bladder)
• Presence of significant bacteriuria without symptoms = asymptomatic bacteriuria
  • Only treat in: pregnancy, pre-urological procedures
  • Do NOT treat in: elderly, catheterized patients, non-pregnant adults (causes resistance without benefit)

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SAQ 2: Laboratory diagnosis of Bacterial Vaginosis (BV).

1. Thin, homogenous gray-white discharge
2. Vaginal pH >4.5
3. Positive whiff test (KOH)
4. Clue cells on wet mount microscopy

• Scores lactobacillus morphotypes (0-4), Gardnerella/Bacteroides morphotypes (0-4), and curved rods/Mobiluncus (0-2)
• Score 0-3 = normal; 4-6 = intermediate; 7-10 = BV

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SAQ 3: Ophthalmia neonatorum - causes, comparison, and management.

• Gonococcal: Ceftriaxone 25-50mg/kg IV (single dose)
• Chlamydial: Erythromycin syrup 50mg/kg/day × 14 days (oral, to eradicate nasopharyngeal carriage too)

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SAQ 4: Modified Thayer Martin (MTM) medium.

• Selective enriched medium for isolating pathogenic Neisseria (N. gonorrhoeae, N. meningitidis) from specimens with mixed flora
• Base: Chocolate agar (lysed blood) - enriched for fastidious organisms
• Supplemented with: glucose, iron, vitamins
• Inhibitory antibiotics (VCN indicator):
  • Vancomycin - inhibits gram-positive organisms
  • Colistin (polymyxin) - inhibits gram-negative rods
  • Nystatin - inhibits fungi/yeasts
• Some formulations also contain trimethoprim to inhibit Proteus swarming
• Incubation: 35-37°C, 5% CO₂, 24-48h
• Gonococci produce: small, gray, translucent, oxidase-positive colonies

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SAQ 5: Non-gonococcal urethritis (NGU).

• Urethritis not caused by N. gonorrhoeae
• Most common cause: Chlamydia trachomatis (serovars D-K) - 30-50%
• Other causes:
  • Ureaplasma urealyticum (~20%)
  • Mycoplasma genitalium (15-25%)
  • Trichomonas vaginalis
  • HSV
  • Adenovirus
• Incubation: 1-3 weeks (longer than gonococcal urethritis)
• Presentation: Dysuria, mild to moderate mucopurulent urethral discharge (less profuse than gonorrhea)
• Gram stain: >5 PMNs/oil-immersion field but no intracellular diplococci
• Treatment: Azithromycin 1g single dose OR Doxycycline 100mg BD × 7 days

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SAQ 6: Pyelonephritis - etiology, pathogenesis, and diagnosis.

• Upper UTI involving the renal parenchyma and pelvicalyceal system
• Most common route: ascending from bladder via ureters
• Hematogenous route: S. aureus (in bacteremia/endocarditis), Mycobacterium tuberculosis (descending/miliary)
• Predisposing factors: VUR, urinary obstruction, pregnancy, diabetes, immunosuppression
• Organisms: E. coli (most common), Klebsiella, Proteus
• Virulence: P-fimbriae (type P pili) are critical - bind globoside receptors on uroepithelium in upper urinary tract
• Acute: Lobar nephronia → abscess formation if severe; grossly: pale cortical abscesses; histology: PMN infiltration of tubules and interstitium
• Chronic pyelonephritis: cortical scarring, blunted calyces, irregular surface

• Urine culture: >10⁵ CFU/mL
• Pyuria, casts (white cell casts pathognomonic), hematuria
• Blood culture: 20% bacteremic
• Imaging (ultrasound/CT): rule out obstruction, abscess

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SAQ 7: Syphilis - causative agent, stages, and serological diagnosis.

1. Primary: Painless chancre (indurated, clean base) at inoculation site; heals in 3-6 weeks; regional lymphadenopathy
2. Secondary (6-8 weeks later): Generalized maculopapular rash (involves palms and soles - KEY), condylomata lata, mucous patches (snail track ulcers), lymphadenopathy, fever, malaise
3. Latent: Early (<1yr) and Late (>1yr); asymptomatic but seroreactive
4. Tertiary (15-40% untreated):
   • Gummas (granulomas): skin, bone, liver
   • Cardiovascular: aortic aneurysm (ascending aorta), aortic regurgitation
   • Neurosyphilis: tabes dorsalis, general paresis of the insane (GPI), Argyll Robertson pupil

• VDRL (Venereal Disease Research Laboratory): flocculation; becomes negative after treatment; used for CSF
• RPR (Rapid Plasma Reagin): card test for serum; quantitative titres for treatment monitoring

• FTA-ABS (Fluorescent Treponemal Antibody Absorption): gold standard
• TPHA / TPPA (T. pallidum Hemagglutination/Particle Agglutination): simple, specific
• EIA/CLIA: automated treponemal tests

• Acute: viral infections (EBV, hepatitis), malaria
• Chronic: SLE, leprosy, IV drug use, antiphospholipid syndrome

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SAQ 8: Trichomonas vaginalis - morphology, pathogenesis, clinical features, and lab diagnosis.

• Only pathogenic protozoan of the urogenital tract
• Flagellated protozoan (4 anterior flagella + 1 recurrent flagellum forming undulating membrane); pear-shaped/pyriform; no cyst stage (only trophozoites)
• Transmitted exclusively by sexual contact
• Infects squamous epithelium of vagina, urethra, and paraurethral glands

• Women: Frothy, yellow-green, profuse vaginal discharge; "strawberry cervix" (colpitis macularis); fishy odor; pH >4.5; itching and burning
• Men: Usually asymptomatic; occasionally urethritis/epididymitis
• Associated with increased HIV transmission risk

• Wet mount microscopy (vaginal discharge + saline): pear-shaped trophozoites with characteristic jerky/tumbling motility - most rapid
• Sensitivity of wet mount: only 50-70%
• Culture (Diamond's medium or InPouch TV): most sensitive
• NAATs: most sensitive and specific (gold standard)
• Pap smear: incidental finding (not reliable diagnostic method)

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SAQ 9: Complications of gonorrhea in men and women.

• Epididymitis (most common local complication)
• Prostatitis
• Urethral stricture (from repeated infections and scarring)
• Infertility (bilateral epididymitis → obstruction)

• Endocervicitis → endometritis → salpingitis
• Pelvic Inflammatory Disease (PID) - most serious complication
• Tubo-ovarian abscess
• Fitz-Hugh-Curtis syndrome - perihepatitis (right upper quadrant pain); violin string adhesions between liver capsule and peritoneum
• Infertility (tubal scarring)
• Ectopic pregnancy (10-fold increased risk)

• More common in women, complement-deficient patients
• Bacteremic phase: fever, migratory polyarthritis, tenosynovitis, pustular/hemorrhagic skin lesions on extremities
• Septic arthritis phase: monoarthritis (knee, wrist most common)

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SAQ 10: Specimen collection for UTI - discuss types with their advantages and disadvantages.

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IMPORTANT ONE-LINERS AND MNEMONICS

• Kass criterion: ≥10⁵ CFU/mL = significant bacteriuria (midstream urine)
• Most common cause of uncomplicated UTI: E. coli
• Most common cause of UTI in young women after E. coli: S. saprophyticus
• Gram stain of gonorrhea: Gram-negative intracellular diplococci in PMNs
• Most common bacterial STI: Chlamydia trachomatis
• Elementary body = infectious form of Chlamydia; Reticulate body = replicating form
• LGV groove sign: inguinal nodes above and below Poupart's ligament separated by groove
• Clue cells = vaginal epithelial cells coated with G. vaginalis → diagnostic of BV
• Nugent score ≥7 = BV
• Strawberry cervix = Trichomonas vaginalis
• Darkfield microscopy = T. pallidum (cannot be cultured)
• VDRL false positive occurs in SLE, leprosy, malaria (biological false positive)
• Modified Thayer Martin agar = selective medium for N. gonorrhoeae (VCN - vancomycin, colistin, nystatin)
• Ophthalmia neonatorum - gonorrhea: day 2-5; chlamydia: day 5-12; chemical: day 1
• Crede's prophylaxis: 1% silver nitrate at birth → prevents gonococcal ophthalmia
• Only protozoan STI: Trichomonas vaginalis (no cyst, only trophozoite)
• NAAT is the most sensitive test for both gonorrhea and chlamydia
• GBS (Group B Strep = S. agalactiae): colonizes female genital tract → transmitted to neonate at birth
• Compliment deficiency (C5-C9): predisposes to disseminated Neisseria infection
• Prostatitis marker: >10 WBCs/high-power field in expressed prostatic secretion (EPS)
• Urease producers causing UTI: Proteus mirabilis (alkalinizes urine → struvite/triple phosphate stones)

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EXPECTED EXAM FORMAT (Apurba Sastry pattern)

1. Classify UTI. Describe etiological agents, pathogenesis, and lab diagnosis of UTI
2. Describe gonorrhea in detail (etiology, pathogenesis, clinical features, diagnosis, treatment)
3. Describe Chlamydia trachomatis with emphasis on clinical syndromes and lab diagnosis
4. Write about sexually transmitted infections - classification and lab diagnosis

1. Significant bacteriuria
2. Non-gonococcal urethritis
3. Ophthalmia neonatorum
4. Bacterial vaginosis and its diagnosis
5. Modified Thayer Martin medium
6. Trichomonas vaginalis
7. Disseminated gonococcal infection
8. LGV (Lymphogranuloma venereum)
9. Syphilis serology
10. Pyelonephritis - etiology and lab diagnosis

• Elementary body vs. reticulate body
• Clue cells
• Nugent score
• Kass criterion
• Crede's prophylaxis
• Groove sign
• Strawberry cervix
• Complicated vs. uncomplicated UTI

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Sources: Medical Microbiology 9e (Murray et al.); Tietz Textbook of Laboratory Medicine 7e; Goldman-Cecil Medicine; Campbell-Walsh Urology. Content aligns with Apurba Sastry Microbiology exam pattern for MD/MBBS examinations.