Gonococcal Infections¶

Chapter 161 | Harrison's 22e · Part 5 – Infectious Diseases: Bacterial · Chapter 161

Key Clinical Points¶

Gonorrhea is a sexually transmitted infection (STI) causing cervicitis, urethritis, proctitis, and conjunctivitis.
Untreated infections may lead to pelvic inflammatory disease (PID), ectopic pregnancy, and infertility in women; epididymitis in men.
Disseminated gonococcemia presents with skin lesions (petechial rash → pustules → necrosis), tenosynovitis, septic arthritis, and rare endocarditis/meningitis.
Ceftriaxone is the preferred first-line treatment for uncomplicated infections due to high efficacy and low resistance rates (<1%).
Epidemiology shows a significant burden in young adults (15–29 years) with increasing global antibiotic resistance.
Diagnosis relies on NAAT, Gram stain (identifying intracellular diplococci), and culture on Thayer-Martin agar.

1. DEFINITION & OVERVIEW¶

• Definition (Harrison's 22e): Gonorrhea is a sexually transmitted infection (STI) of epithelium and commonly manifests as cervicitis, urethritis, proctitis, and conjunctivitis.

• Clinical Sites: Infection of mucosal surfaces of the genital tract, rectum, and conjunctiva.

• Complications of Untreated Infection: • Females: Endometritis, salpingitis, tuboovarian abscess, bartholinitis, peritonitis, perihepatitis (Fitz-Hugh-Curtis syndrome), ectopic pregnancy, and infertility. • Males: Periurethritis, epididymitis. • Neonates: Ophthalmia neonatorum.

• Systemic Manifestations: Disseminated gonococcemia → dermatologic lesions (petechial rash, pustules), tenosynovitis, septic arthritis (commonly knee, wrist), and rare endocarditis/meningitis.

2. MICROBIOLOGY¶

• Organism: Neisseria gonorrhoeae • Characteristics: • Gram-negative diplococcus. • Requires human host for survival. • Polyploidy (3 genome copies per cell) → enables antigenic variation. • Oxidase positive. • Distinguished by glucose utilization on selective media.

• Resistance Profiles: • Ceftriaxone: Resistance reported in <1% of isolates globally. • Fluoroquinolones: Resistance prevalent in North America, Europe, and Asia. • Rifampin: Fails to eradicate carriage in 15–20% of cases.

3. EPIDEMIOLOGY¶

• Global Burden: • WHO estimate: 82.4 million cases in adults aged 15–49 years (2020).

• United States Data: • 710,000 reported cases in 2021 (up 136% since 2009 low).

• Demographic Trends: • High Attack Rates: 15–24 year old women (730.5/100k) and 20–29 year old men (813.6/100k). • Ethnic Disparities: African Americans (652.9/100k) vs. Asian descent (37.8/100k).

• Transmission Dynamics: • Asymptomatic carriage common (especially in males). • Underreporting due to self-treatment and lack of symptoms.

4. CLINICAL MANIFESTATIONS¶

• Local Manifestations: • Cervicitis: Purulent vaginal discharge, dysuria. • Urethritis: Dysuria, mucopurulent urethral discharge. • Proctitis: Rectal discharge, tenesmus. • Conjunctivitis: Acute conjunctival hyperemia, purulent discharge.

• Systemic Complications: • Disseminated Gonococcemia: • Dermatologic Progression: Petechial rash → pustular lesions → mature lesions with central necrosis (Figure 161-2). • Joint Involvement: Septic arthritis (commonly knee, wrist). Note: Unlike reactive arthritis (which favors lower extremities and the spine/SI joints), gonococcal arthritis is typically asymmetric and involves both large and small joints (Figure 161-3). • Pelvic Inflammatory Disease (PID): Lower abdominal pain, fever, irregular bleeding. • Neonatal Ophthalmia Neonatorum: Bilateral conjunctivitis within 5–14 days postpartum.

5. DIAGNOSTIC APPROACH¶

Initial Screening: Nucleic acid amplification tests (NAATs) for urine, urethral, or vaginal specimens.
Microscopic Examination: Gram stain of genital secretions → identify intracellular diplococci in polymorphonuclear cells (Figure 161-1).
Culture: Growth on Thayer-Martin agar (requires CO2 incubation).

• Differential Diagnosis: • Chlamydia trachomatis: Similar symptoms but slower progression. • Herpes simplex virus (HSV): Characterized by vesicular lesions. • Syphilis: Primary stage presents as a chancre.

6. MANAGEMENT & TREATMENT¶

Uncomplicated Infections (Cervix, Urethra, Pharynx, or Rectum): • First-line: Ceftriaxone (500 mg IM, single dose). • Co-infection Coverage: Add Doxycycline (100 mg orally twice a day for 7 days) if chlamydial infection cannot be excluded. • Alternative Regimens (if Ceftriaxone is not available): • Option A: Gentamicin (240 mg IM, single dose) + Azithromycin (2 g orally as a single dose). • Option B: Cefixime (800 mg PO, single dose) OR Spectinomycin (2 g IM, single dose) + Doxycycline (100 mg orally twice a day for 7 days).
Pharyngeal/Gonococcal Pharyngitis: • Ceftriaxone (500 mg IM).
Pregnancy Management: • Ceftriaxone preferred over fluoroquinolones.
Ophthalmia Neonatorum: • Ceftriaxone (25–50 mg/kg IV, single dose, not to exceed 125 mg).
Partner Management: • Expedited Partner Therapy (EPT): Recommended for all cases. • Chemoprophylaxis: Ceftriaxone (250 mg IM) for close contacts.
Other Conditions: • Pelvic Inflammatory Disease: See Chapter 141. • Meningitis/Endocarditis: Refer to specific clinical guidelines.

• Haemophilus influenzae (Figure 162-1, Table 162-1): • Type b (Hib): Ribosyl-ribitol phosphate capsule; causes meningitis/invasive infections in children. • Non-typeable: Unencapsulated; causes otitis media and lower respiratory tract infections in adults. • Epidemiology: Significant burden from non-typeable strains and other serotypes (Hia, Hic, Hid, Hie, Hif) in infants (<1) and elderly (≥65).

• Moraxella catarrhalis & H. influenzae (Figure 162-2): • Significant role in community-acquired pneumonia (CAP) and exacerbations of COPD.

• Chancroid (Figure 162-3): • Caused by Haemophilus ducreyi. • Clinical features: Soft genital ulcers and associated inguinal adenitis (bubo).

Reference Tables¶

TABLE 161-1 Recommended Treatment for Gonococcal Infections: Adapted from the 2021 Guidelines for Gonococcal Infection…¶

Harrison's 22e, p.1259

DIAGNOSIS	TREATMENT OF CHOICEa
Uncomplicated gonococcal infection of the cervix, urethra, pharynx,b or rectum
First-line regimen	Ceftriaxone (500 mg IM, single dose)
	plus
	Doxycycline (100 mg orally twice a day for 7 days) for treatment of chlamydial infection if chlamydial infection cannot be excluded
Alternative regimens if ceftriaxone is not available	Gentamicin (240 mg IM, single dose) plus azithromycin (2 g orally as a single dose)c or Cefixime (800 mg PO, single dose) or spectinomycin (2 g IM, single dose)d,e plus Doxycycline (100 mg orally twice a day for 7 days) for treatment of chlamydial infection if chlamydial infection cannot be excluded
Pelvic inflammatory disease	See Chap. 141
Ophthalmia neonatorumg	Ceftriaxone (25–50 mg/kg IV, single dose, not to exceed 125 mg)
Meningitis or endocarditis	See text for specific recommendationsk

TABLE 162-1 Characteristics of Type b and Nontypeable Strains of Haemophilus influenzae FEATURE Capsule Pathogenesis…¶

Harrison's 22e, p.1260

FEATURE	TYPE b STRAINS	NONTYPEABLE STRAINS
Capsule	Ribosyl-ribitol phosphate	Unencapsulated
	Invasive infections due to hematogenous spread
Clinical manifestations	Meningitis and invasive infections in incompletely immunized infants and children	Otitis media in infants and children; lower respiratory tract infections in adults with chronic bronchitis
	Basically clonal
Vaccine	Highly effective conjugate vaccines	Protein D used as carrier protein in pneumococcal vaccine approved in Europe: GSK Synflorix. Others under development