Neisseria gonorrhoeae

Background

• Causes gonorrhea

Microbiology

• Gram-negative diplococcus within the genus Neisseria
• Resistance
  • MDR gonorrhea: resistance to one of azithromycin or a cephalosporin
  • XDR if resistance to both azithromycin and a cephalosporin

Epidemiology

• Resistance
  • About 50% resistance to fluoroquinolones
  • Rates of MDR gonorrhea is increasing in Canada, mostly driven by azithromycin resistance
  • XDR gonorrhea is still rare in Canada 1

Mechanisms of Resistance

• β-lactamases, most commonly a TEM-1-type contained on a Pc^R plasmid
• Altered penicillin-binding protein PBP-2, encoded by penA
• Altered or downregulated porins, encoded by penB
• Increased efflux pump, encoded by mtr

Clinical Manifestations

Genital Infections

• Causes cervicitis and urethritis
• In women, up to 70% are asymptomatic
  • In symptomatic women, the incubation period is about 10 days, followed by vaginal pruritis or mucopurulent discharge
  • May have intermenstrual bleeding or menorrhagia
• In men and women with urethritis, it is usually asymptomatic
  • Incubation period is usually about 3 to 5 days, followed by urethral discharge and dysuria
• Epididymitis in men is more commonly caused by Chlamydia trachomatis

Pelvic Inflammatory Disease

• See Pelvic inflammatory disease, of which about 40% of cases are caused by Neisseria gonorrhoeae
• Pelvic and abdominal pain, vaginal bleeding, and dyspareunia
• May be febrile and acutely unwell

Fitz-Hugh-Curtis Syndrome

• Aka perihepatitis, with inflammation of Glisson's capsule around the liver
• More often associated with Chlamydia trachomatis

Bartholinitis

• Inflammation of Bartholin's glands, which are behind the labia
• Labial pain, swelling, tenderness, and discharge

Anorectal Gonorrhea

• Often asymptomatic
• Can cause anorectal pain, discharge, and pruritis
• Anal intercourse not required, especially in women

Disseminated Gonococcal Infection

• Occurs in about 1% of patients with gonorrhea, and most strains do not cause urethritis
  • Risk factors include female sex, menstruation, pregnancy, and terminal complement deficiency
• Classically presents with either septic arthritis, or with a triad of tenosynovitis (often of wrists) dermatitis (with pustular lesions), and arthritis
• Diagnosed with genital testing for gonorrhea, ± blood cultures or arthrocentesis
• Other (rare) sites of dissemination include endocarditis, meningitis, and osteomyelitis

Conjunctivitis

• Occurs in infants born to untreated, infected mothers, and rarely from spread by fomites or flies

Differential Diagnosis

• Other causes of urethritis or septic arthritis or proctitis

Management

• Anogenital and pharyngeal infection in people ≥9 years of age
  • First-line: ceftriaxone 250 mg IM once plus azithromycin 1 g PO once
  • Second-line: gentamicin 240 mg IM once (in 2 doses) plus azithromycin 2 g PO once
  • Second-line: ciprofloxacin 500 mg PO once plus azithromycin 2 g PO once
• Disseminated gonococcal infection
  • Arthritis: ceftriaxone 2 g IV q24h for 7 days, plus azithromycin 1 g PO once
  • Meningitis: ceftriaxone 2 g IV q24h for 10-14 days, plus azithromycin 1 g PO once
  • Endocarditis: ceftriaxone 2 g IV q24h for 28 days, plus azithromycin 1 g PO once
  • Ophthalmia: ceftriaxone 2 g IV once, plus azithromycin 1 g PO once
• Repeat screening at 6 months

Test of Cure

• Done at 3 to 7 days if by culture or 14 to 21 days if NAAT
• Indications include:
  • Pharyngeal infection
  • Persistent signs or symptoms
  • Treated without ceftriaxone
  • Treated with fluoroquinolone, without susceptibility testing
  • Epidemiologic link to a resistant case
  • Documented microbiologic resistance
  • Epidemiologic link to treatment failure
  • Previous treatment failure
  • Uncertain adherence to treatment
  • Reexposure to untreated partener
  • Pregnancy
  • Disseminated gonococcal infection
  • Pediatric patient
  • Pelvic inflammatory disease with documented gonorrhea
  • Therapeutic abortion (increased risk of developing PID)

Further Reading

• Canadian Guidelines on Sexually Transmitted Infections