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Genitourinary Tract Microbiology - Comprehensive Chapter

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SECTION 1: NORMAL FLORA OF THE GENITOURINARY TRACT

1.1 Urinary Tract

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1.2 Vaginal Flora

• Anaerobic Gram-negative rods
• Gram-positive cocci
• Candida spp. (yeasts)

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1.3 Bacterial Vaginosis (BV)

• Vaginal discharge with a characteristic "fishy" (amine) odor
• Clue cells - epithelial cells coated with bacteria visible on microscopy
• Higher pH (>4.5) and greater microbial diversity
• Increased anaerobes

• Gardnerella vaginalis (most associated)
• Mobiluncus spp.
• Anaerobes (Prevotella, Peptostreptococcus)
• Mycoplasma hominis

1. Homogeneous, thin, white discharge
2. Clue cells on wet mount
3. pH >4.5
4. Positive whiff test

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SECTION 2: URINARY TRACT INFECTIONS (UTIs)

2.1 Epidemiology and Pathogenesis

• Female sex
• Sexual activity (introduction of organisms)
• Pregnancy (ureteral dilation, bladder atony)
• Urologic abnormalities (obstruction, reflux, calculi)
• Catheterization (bypasses urethral defenses)
• Diabetes mellitus
• Immunosuppression
• Incomplete bladder emptying

2.2 Classification

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2.3 Causative Organisms

• E. coli, Klebsiella, Pseudomonas, Enterococcus, Candida spp.
• Polymicrobial infections more common

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2.4 Virulence Factors of Uropathogenic E. coli (UPEC)

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2.5 Diagnosis

• Midstream clean-catch specimen
• Catheterized specimen
• Suprapubic aspirate (gold standard - any growth significant)

• ≥10⁵ CFU/mL in midstream specimen: significant
• ≥10³ CFU/mL in symptomatic women: diagnostic
• Any growth in suprapubic aspirate: significant

• Leukocyte esterase: Indicates pyuria (WBCs in urine)
• Nitrite test: Positive if nitrate-reducing bacteria (E. coli, Klebsiella, Proteus) present; NOT positive for Enterococcus, Pseudomonas, S. saprophyticus

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2.6 Treatment

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SECTION 3: SEXUALLY TRANSMITTED INFECTIONS (STIs) - BACTERIAL

3.1 Gonorrhea (Neisseria gonorrhoeae)

Bacteriology

• Oxidase positive, catalase positive
• Acid from glucose only (not maltose - differentiates from N. meningitidis)
• Grow best on chocolate agar (or Thayer-Martin/NYC/ML selective media) supplemented with CO₂
• Colonies: small, smooth, non-pigmented; appear at 18-24 hours; 2-4 mm at 48 hours
• More fragile than meningococci; lack a polysaccharide capsule

Outer Membrane Virulence Factors

Pathogenesis

1. Attachment: Pili and Opa proteins attach to receptors (CD46, CD66, integrins) on nonciliated epithelial cells
2. Active twitching motility of pili moves microcolonies across the cell surface
3. Phagocytosis induction: Por1BA triggers signaling cascades → microfilaments/microtubules engulf bacteria
4. Transcytosis: Bacteria pass through the host cell and exit through the basal membrane into the submucosa
5. Survival: LOS sialylation binds Factor H → blocks C3b deposition; pili + Opa interfere with phagocytic killing; catalase upregulation resists oxidative killing

Clinical Diseases

• Urethritis: Incubation 2-5 days; dysuria and purulent urethral discharge (yellow-green); 10% asymptomatic
• Epididymitis: Extension from urethra; unilateral scrotal pain and swelling
• Prostatitis: Fever, perineal pain, urinary symptoms
• Proctitis (MSM): rectal pain, discharge

• Cervicitis: Most common presentation; mucopurulent endocervical discharge; often asymptomatic
• Urethritis: Dysuria, frequency; may coexist with cervicitis
• Bartholin gland abscess: Swollen, painful unilateral labial mass
• Pelvic Inflammatory Disease (PID): Extension up fallopian tubes causing salpingitis; fever, lower abdominal pain, cervical motion tenderness; complications: infertility and ectopic pregnancy from tubal scarring
• Tubo-ovarian abscess: Serious complication of PID

Important: PID may also be caused by Chlamydia trachomatis, anaerobes, or mixed organisms ascending the same route.

• Pharyngitis: Exudative or asymptomatic; from orogenital contact
• Conjunctivitis (Ophthalmia Neonatorum): In neonates exposed during delivery; severe purulent conjunctivitis that can lead to blindness; prevented by 1% silver nitrate or erythromycin eye drops at birth
• Disseminated Gonococcal Infection (DGI):
  • Occurs in ~1-3% of untreated infections
  • Bacteremic phase: fever, migratory polyarthralgia, petechial/maculopapular/pustular skin rash
  • Risk factors: complement deficiency (C5-C9 deficiency)
  • Septic arthritis: Purulent arthritis affecting large joints (elbow, knee); gonococci culturable from joint pus
  • Rare: endocarditis, meningitis

Diagnosis

Treatment & Resistance

• Current treatment of choice: Ceftriaxone (IM/IV) + azithromycin (dual therapy due to co-infection with Chlamydia and rising resistance)
• Antimicrobial resistance: Progressive resistance - to penicillin (via β-lactamase - PPNG), tetracycline (TRNG), fluoroquinolones, and now emerging high-level resistance to cephalosporins and azithromycin
• No effective vaccine available due to antigenic variation of pili and Opa proteins
• Contact tracing is essential

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3.2 Syphilis (Treponema pallidum subsp. pallidum)

The Organism

• Dimensions: 0.2 μm wide × 5-15 μm long
• Regular spiral coils spaced 1 μm apart
• Actively motile - rotates around endoflagella (periplasmic flagella)
• Cannot be cultured on artificial media, eggs, or tissue culture (unique among human pathogens)
• Survives 3-6 days at 25°C in suspending fluid; 24 hours in blood at 4°C
• Killed rapidly by drying and temperatures above 42°C
• Penicillin-sensitive (no resistance documented); slow killing rate due to slow division time (~30 hours)

• Does NOT stain well with aniline dyes (Gram stain useless)
• Visible with dark-field microscopy or immunofluorescence
• In tissues: visualized with silver impregnation methods (Warthin-Starry, Levaditi stains)

Pathogenesis and Virulence

• Hyaluronidase: Breaks down hyaluronic acid in tissue ground substance, facilitating invasion
• Outer membrane proteins with lipid anchors: poorly accessible to antibodies - explains immune evasion
• Endoflagella: In periplasmic space; mediate motility

Clinical Stages of Syphilis

• Incubation: 10-90 days (average ~21 days)
• Chancre: Painless, indurated ulcer with clean base and raised edges at inoculation site
• Accompanied by regional non-tender lymphadenopathy
• Spontaneous resolution in 3-6 weeks
• Highly infectious

• Spirochetemia; dissemination throughout body
• Skin rash: Classic palmoplantar involvement (maculopapular); affects palms and soles
• Condylomata lata: Moist, flat, highly infectious wart-like lesions in moist intertriginous areas
• Mucous patches: Highly infectious whitish plaques on oral/genital mucosa
• Systemic: fever, malaise, lymphadenopathy, alopecia, hepatitis, nephritis, meningitis
• Spontaneous resolution in weeks to months

• Early latent (<1 year): Still infectious; 25% relapse with secondary lesions
• Late latent (>1 year): Non-infectious; may persist for life

• Gummas: Granulomatous lesions in skin, bone, liver; few organisms
• Cardiovascular syphilis: Aortitis → aortic aneurysm (ascending aorta), aortic regurgitation
• Neurosyphilis:
  • Meningovascular: stroke-like syndromes
  • General paresis: dementia, psychiatric changes
  • Tabes dorsalis: posterior column degeneration; Argyll Robertson pupil, lightning pains, Romberg sign

• Spirochetes cross placenta after 16th week of gestation
• Early: Rhinitis ("snuffles"), maculopapular rash, hepatosplenomegaly, osteitis
• Late: Hutchinson's triad (interstitial keratitis, deafness, notched incisors), saddle nose, saber shins

Serological Diagnosis

• VDRL (Venereal Disease Research Laboratory) and RPR (Rapid Plasma Reagin)
• Detect antibodies to cardiolipin-cholesterol-lecithin complex (reagin antibodies)
• Quantitative (titer reflects disease activity; falls with successful treatment)
• False positives: SLE, antiphospholipid syndrome, pregnancy, viral infections, drug use
• Used for screening and monitoring treatment response

• FTA-ABS (Fluorescent Treponemal Antibody Absorbed)
• TP-PA (T. pallidum Particle Agglutination)
• TPHA / MHA-TP
• EIA/CIA (automated, increasingly used for high-throughput screening)
• Remain positive for life regardless of treatment (cannot be used to monitor response)
• Positive FTA-ABS in newborn CSF indicates congenital infection

Treatment

• Penicillin G benzathine (IM) is the drug of choice for all stages
• Primary/secondary/early latent: Single dose
• Late latent/tertiary: 3 doses over 3 weeks
• Neurosyphilis: IV aqueous penicillin G for 10-14 days
• Penicillin allergy: Doxycycline (non-pregnant); desensitize and treat with penicillin in pregnancy

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3.3 Chlamydial Infections (Chlamydia trachomatis)

The Organism

1. EB attaches to and enters host cell by endocytosis
2. EB differentiates into RB within membrane-bound inclusion
3. RB replicates by binary fission (36-48 hour cycle)
4. RB condenses back to EB
5. Inclusion ruptures, releasing EBs to infect adjacent cells

• EBs: Stain purple with Giemsa stain
• RBs: Stain blue with Giemsa stain
• C. trachomatis inclusions: Stain brown with iodine (glycogen matrix) - distinguishes from C. pneumoniae and C. psittaci
• Immunofluorescence: Inclusions glow bright yellow-green with labeled antibodies
• Gram-negative or variable - Gram stain NOT useful

Genital Tract Infections (Serovars D-K)

• Non-gonococcal urethritis (NGU): Most common STI in men; dysuria, mucopurulent urethral discharge (often watery/clear vs. the yellow discharge of gonorrhea); many asymptomatic
• Epididymitis in young men
• Proctitis (MSM)
• Reiter's syndrome (Reactive arthritis): Urethritis + arthritis + conjunctivitis/uveitis; triggered by chlamydial infection

• Cervicitis: Mucopurulent discharge; hypertrophic cervix ("strawberry cervix"); often asymptomatic
• Urethritis: Dysuria, "sterile pyuria" (WBCs but negative standard culture)
• Pelvic Inflammatory Disease (PID): Ascending infection; salpingitis; infertility and ectopic pregnancy
• Perihepatitis (Fitz-Hugh-Curtis syndrome): Extension of PID to liver capsule; right upper quadrant pain; violin-string adhesions between liver and abdominal wall

• Inclusion conjunctivitis: Purulent conjunctivitis appearing 5-14 days after birth; treated with erythromycin eye drops
• Neonatal pneumonia: Afebrile, staccato cough; bilateral interstitial infiltrates; at 2-12 weeks of age

Lymphogranuloma Venereum (LGV) - Serovars L1, L2, L3

1. Primary lesion: Small, transient, painless papule or vesicle on genitalia; often unnoticed; heals in days
2. Secondary (Inguinal) stage: Painful inguinal lymphadenopathy (buboes); nodes coalesce, become fluctuant, suppurate; overlying skin turns purplish; "groove sign" (nodes above and below Poupart's ligament); systemic symptoms: fever, headache, arthralgias
3. Tertiary (Genitoanorectal) stage: Fibrosis, lymphatic obstruction, rectal strictures; elephantiasis of penis, scrotum, or vulva

• NAAT (PCR) on swabs - detects but cannot differentiate LGV from D-K serovars
• Culture in McCoy cells
• Serology: CF titer >1:64 or rising titer
• Biopsy showing granulomatous inflammation

Diagnosis of Urogenital Chlamydia (D-K)

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3.4 Herpes Simplex Virus - Genital Herpes (HSV-2 > HSV-1)

• Primary infection: Painful vesicles on genital/perianal areas that ulcerate; bilateral tender inguinal lymphadenopathy; systemic symptoms (fever, malaise); lesions last 2-3 weeks
• Recurrences: HSV-2 recurs more frequently than HSV-1; often milder; preceded by prodromal tingling/burning
• Asymptomatic shedding: Major source of transmission
• Neonatal herpes: Acquired during delivery from active maternal lesions; can cause severe disseminated infection, encephalitis, or localized skin/eye disease
• Diagnosis: PCR (most sensitive), viral culture (cell lines), DFA, Tzanck smear (multinucleated giant cells - not specific)
• Treatment: Acyclovir, valacyclovir, famciclovir; daily suppressive therapy reduces recurrences and transmission

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3.5 Trichomonas vaginalis

• Exists only as trophozoite (no cyst stage)
• Pear-shaped (pyriform), ~20 μm long × 10 μm wide
• Four free anterior flagella + one flagellum forming an undulating membrane
• Sexually transmitted

• Women: Profuse, frothy, yellow-green vaginal discharge; vulval pruritus; burning; local tenderness; cervical petechiae ("strawberry cervix")
• Men: Usually asymptomatic; ~10% have thin white urethral discharge; may infect prostate, seminal vesicles
• Incubation period: 5-28 days
• Estimated 3.7 million infections in US; only 30% symptomatic

• Wet mount: Motile pear-shaped flagellated protozoa (sensitivity ~60-70%)
• NAAT: Highest sensitivity (>95%)
• Culture (CPLM or Diamond's medium)
• Vaginal pH >4.5

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3.6 Other Important STIs

Chancroid (Haemophilus ducreyi)

• Painful soft genital ulcer (vs. painless chancre of syphilis) with undermined edges
• Tender suppurative inguinal lymphadenopathy (bubo)
• Common in developing countries; co-factor for HIV transmission
• Diagnosis: Culture on special media (difficult); clinical
• Treatment: Azithromycin 1g single dose or ceftriaxone

Granuloma Inguinale (Donovanosis) (Klebsiella granulomatis)

• Chronic painless genital ulcer with beefy-red granulation tissue; progressive tissue destruction
• Donovan bodies: Intracellular organisms in mononuclear cells on Giemsa or Wright stain (pathognomonic)
• Treatment: Doxycycline × 3 weeks or azithromycin

Human Papillomavirus (HPV)

• Condylomata acuminata (genital warts): Types 6, 11 (low risk)
• Cervical cancer: Types 16, 18 (high risk oncogenic)
• Diagnosis: Clinical/colposcopy; Pap smear cytology; HPV DNA testing
• Treatment: Podophyllin, TCA, cryotherapy, imiquimod; vaccines (Gardasil 9 - 9-valent)

Genital Mycoplasmas

• Mycoplasma genitalium: Increasingly recognized as cause of NGU in men and cervicitis/PID in women; resistance to azithromycin emerging
• Ureaplasma urealyticum: Urease-producing; associated with NGU, preterm labor, neonatal disease
• M. hominis: Associated with BV, PID; highly prevalent in women with multiple sexual partners

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SECTION 4: INFECTIONS OF SPECIFIC STRUCTURES

4.1 Prostatitis

4.2 Epididymo-orchitis

4.3 Pelvic Inflammatory Disease (PID)

1. Neisseria gonorrhoeae
2. Chlamydia trachomatis

• Anaerobes (Bacteroides, Peptostreptococcus, Prevotella)
• Gardnerella vaginalis
• Enteric Gram-negative rods

• Inpatient: Cefoxitin/cefotetan + doxycycline, OR clindamycin + gentamicin
• Outpatient: Ceftriaxone IM + doxycycline ± metronidazole × 14 days

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SECTION 5: UROGENITAL TUBERCULOSIS

• Mycobacterium tuberculosis can seed the kidneys and genital tract hematogenously from primary lung focus
• Renal TB: "Sterile pyuria" (WBCs in urine but negative standard cultures); granulomatous inflammation with caseous necrosis; calcification
• Epididymitis - painless or mildly tender; classic "beaded" appearance on palpation
• Fallopian tube TB: Major cause of infertility in endemic regions
• Diagnosis: Early morning urine × 3 for AFB smear and culture (Lowenstein-Jensen medium); PCR; histology
• Treatment: Standard anti-TB regimen (2HRZE/4HR)

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SECTION 6: FUNGAL INFECTIONS OF THE GENITOURINARY TRACT

6.1 Vulvovaginal Candidiasis (VVC)

• Causative organism: Candida albicans (75-80%); C. glabrata, C. tropicalis (non-albicans increasing)
• Predisposing factors: Antibiotics (disrupt Lactobacillus), diabetes, pregnancy, immunosuppression, OCPs
• Clinical features: Vulval pruritus, burning; thick "cottage cheese" (curd-like) white discharge; satellite lesions; vulvovaginal erythema
• Diagnosis:
  • Wet mount with 10% KOH: Pseudohyphae and budding yeast cells
  • Culture on Sabouraud's dextrose agar
  • pH: <4.5 (distinguishes from BV and Trichomoniasis)
• Treatment: Azole antifungals (fluconazole 150mg PO single dose or topical azoles); recurrent VVC requires longer courses

6.2 Candidal UTI

• Common in catheterized patients, ICU patients, diabetics, post-antibiotics
• Often asymptomatic; treat if symptomatic or immunosuppressed
• Treatment: Fluconazole (preferred for C. albicans); amphotericin B bladder irrigation for resistant cases

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SECTION 7: SUMMARY TABLE - GU PATHOGENS AT A GLANCE

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SECTION 8: IMPORTANT CLINICAL POINTS

1. Urethral discharge differential:
   • Yellow-green purulent → N. gonorrhoeae
   • Watery/mucopurulent, clear → C. trachomatis
   • Always co-treat for both (30-50% co-infection rate)
2. Painless ulcer → Syphilis (chancre); Granuloma inguinale Painful ulcer → Chancroid (H. ducreyi); Herpes simplex
3. Sterile pyuria (WBCs in urine, negative standard culture):
   • C. trachomatis urethritis
   • Urogenital tuberculosis
   • Trichomonas vaginalis
4. Newborn protection:
   • Against gonococcal ophthalmia: Silver nitrate 1% or erythromycin eye drops at birth
   • Against chlamydial conjunctivitis: Erythromycin eye drops
5. Complement deficiency (C5-C9): Predisposes to recurrent Neisseria infections (both gonococcal DGI and meningococcemia)
6. Antibiotic resistance: N. gonorrhoeae has developed resistance to penicillin (PPNG - β-lactamase producing), tetracycline (TRNG), fluoroquinolones, and now cephalosporins - a major public health threat; M. genitalium now shows high azithromycin resistance
7. PID complications: Infertility, ectopic pregnancy, chronic pelvic pain, tubo-ovarian abscess - all related to fallopian tube scarring

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• Sherris & Ryan's Medical Microbiology, 8th Edition (Genitourinary Tract, Ch. 1 Normal Flora + Ch. 30 Neisseria)
• Jawetz, Melnick & Adelberg's Medical Microbiology, 28th Edition (Chlamydia, Treponema, Trichomonas chapters)
• Medical Microbiology, 9th Edition (Murray) (Neisseria, UTI pathogens)
• Goldman-Cecil Medicine (Genitourinary Tract Infections)
• Bailey and Love's Surgery (Genitourinary Tract section)

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Chapter Summary

What's covered:

Key Textbook Images Included:

• Vaginal Gram smear (Sherris & Ryan, p. 37) - showing Lactobacilli, yeast, and mixed flora
• N. gonorrhoeae electron micrograph - pili + attachment to urethral epithelial cells
• Tubo-ovarian abscess gross specimen - PID complication