Second most reported STI in the US — gram-negative diplococcus (Neisseria gonorrhoeae); rising antimicrobial resistance has shaped current ceftriaxone-based therapy.
Also known as: gonorrhea, Neisseria gonorrhoeae, GC, the clap
Overview
Sexually transmitted infection caused by Neisseria gonorrhoeae, a fastidious gram-negative diplococcus. Infects mucosal columnar epithelium (cervix, urethra, rectum, pharynx, conjunctiva). Disseminated infection (DGI) involves skin, joints, and rarely endocardium/meninges.
Epidemiology
Over 700,000 US cases in 2022 (CDC); second most reported notifiable disease. Disproportionately affects young adults, MSM, and Black populations. Antimicrobial resistance is a major and growing concern — particularly emerging cephalosporin resistance.
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Question 1Infectious DiseaseMedium
A 23-year-old man has urethral discharge. NAAT confirms Neisseria gonorrhoeae. Which of the following is the most appropriate treatment?
AOral azithromycin monotherapy
BIntramuscular ceftriaxone dose
COral cefixime single oral dose
DOral ciprofloxacin single dose
Reveal answer & full explanation
Correct answer: B — Intramuscular ceftriaxone dose
AOral azithromycin monotherapy
BIntramuscular ceftriaxone dose✓
COral cefixime single oral dose
DOral ciprofloxacin single dose
Why Intramuscular ceftriaxone dose is correct
A single intramuscular dose of ceftriaxone is the CDC first-line treatment for uncomplicated urogenital gonorrhea.
Doxycycline is added when chlamydial coinfection has not been excluded.
Untreated gonorrhea can cause epididymitis, disseminated infection, and infertility.
Why the others are wrong
Oral ciprofloxacin single dose — Fluoroquinolones were dropped for gonorrhea because of widespread resistance; using ciprofloxacin risks treatment failure.
Oral azithromycin monotherapy — Azithromycin alone is inadequate for gonorrhea given rising macrolide resistance and is no longer recommended as monotherapy.
Oral cefixime single oral dose — Oral cefixime is only a backup when ceftriaxone is unavailable; it achieves lower tissue levels and is not first-line.
Question 2Infectious DiseaseMedium
A 24-year-old sexually active woman presents with 4 days of fever and migratory joint pain that started in her knees and has moved to her right wrist. She reports a new sexual partner in the past month and is currently menstruating. On exam, temperature is 38.4°C (101.1°F). She has pain and swelling along the tendon sheaths of her right wrist and several fingers, and a few scattered pustular lesions on the dorsa of her hands and forearms. Arthrocentesis of the wrist yields cloudy fluid with a negative Gram stain. Which of the following is the most likely diagnosis?
AReactive post-enteric arthritis
BDisseminated gonococcal infection
CPolyarticular rheumatoid arthritis
DStaphylococcal septic arthritis
Reveal answer & full explanation
Correct answer: B — Disseminated gonococcal infection
AReactive post-enteric arthritis
BDisseminated gonococcal infection✓
CPolyarticular rheumatoid arthritis
DStaphylococcal septic arthritis
Why Disseminated gonococcal infection is correct
The classic DGI arthritis-dermatitis syndrome is the triad of migratory asymmetric polyarthralgia/arthritis, tenosynovitis (especially wrists and fingers), and pustular skin lesions on the extremities, with fever.
DGI characteristically strikes young, sexually active patients, and women are at higher risk around menses and during pregnancy, fitting this menstruating 24-year-old with a recent new partner.
Joint fluid Gram stain and culture are frequently negative in the arthritis-dermatitis form because it is largely immune/bacteremic rather than purulent; diagnosis relies on NAAT or culture of genital and extragenital sites plus blood cultures.
CDC 2021 treatment of DGI is ceftriaxone 1 g IV/IM daily for at least 7 days plus empiric chlamydia coverage; recurrent DGI should prompt evaluation for terminal complement deficiency (C5-C9, order CH50).
Why the others are wrong
Reactive post-enteric arthritis is an asymmetric oligoarthritis with conjunctivitis and urethritis after a GU/GI infection (HLA-B27 associated); it does not produce pustular skin lesions with tenosynovitis and fever in this acute STI context.
Staphylococcal septic arthritis is the most common bacterial monoarthritis, but it produces a single hot purulent joint with a frequently positive Gram stain, not migratory polyarthralgia, tenosynovitis, and pustular skin lesions.
Polyarticular rheumatoid arthritis is a symmetric small-joint polyarthritis with morning stiffness developing over weeks to months; it does not present acutely with fever, pustular skin lesions, and a recent sexual-exposure history.
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Age <25, multiple partners, new partner within 60 days
Inconsistent condom use
Sex work, MSM (pharyngeal/rectal infection)
Concurrent STIs (especially chlamydia)
Mother with untreated gonorrhea (neonatal ophthalmia)
Pathophysiology
Pili and outer membrane proteins (Opa) mediate attachment to columnar epithelium. Bacteria invade epithelial cells, induce inflammation, and produce purulent exudate. Antigenic variation of pili allows immune evasion and reinfection. Disseminated infection occurs in 0.5-3%, often associated with complement deficiency (C5-C9).
Clinical presentation
Symptoms
Men (urethritis): purulent yellow-green urethral discharge, dysuria 2-5 days post-exposure; ~10% asymptomatic
Neonate: copious purulent conjunctival discharge with eyelid edema
Classic findings
Young sexually active patient with copious purulent urethral discharge — gonorrhea until proven otherwise. DGI: polyarthralgia, tenosynovitis, and pustular skin lesions in a young woman around menses or pregnancy.
Differential diagnosis
Chlamydia — Less purulent discharge, frequent coinfection; treat both if clinical PID
Mycoplasma genitalium — Persistent urethritis after treatment; NAAT
UTI — Dysuria with pyuria, no urethral discharge; positive urine culture
Septic arthritis from other pathogens — S. aureus most common monoarthritis; arthrocentesis with Gram stain/culture
Reactive arthritis — Asymmetric oligoarthritis with conjunctivitis/urethritis after GU/GI infection; HLA-B27
Diagnostic workup
Diagnostic criteria
Positive NAAT, culture, or Gram stain (men with symptomatic urethritis) for N. gonorrhoeae.
Labs
Nucleic acid amplification test (NAAT) — preferred for genital, rectal, and pharyngeal sites (sensitivity >95%)
Specimens: first-catch urine or urethral swab (men), endocervical or vaginal swab (women), pharyngeal and rectal swabs as exposure dictates
Culture (with antimicrobial susceptibility testing) — important when treatment failure suspected; required at extragenital sites in some labs
Gram stain of urethral discharge (men): gram-negative intracellular diplococci have high PPV in symptomatic men
Test for concurrent chlamydia, syphilis, HIV; consider hepatitis B/C
Blood and joint cultures for DGI; arthrocentesis with Gram stain/culture/NAAT
Imaging
Pelvic ultrasound if PID/tubo-ovarian abscess suspected
Joint imaging for septic arthritis
Diagnostic algorithm
Site/Syndrome
Therapy
Co-coverage
Urogenital/rectal/pharyngeal
Ceftriaxone 500 mg IM x 1
Doxycycline 100 mg BID x 7 d if chlamydia not excluded
Pharyngeal — test of cure
7-14 days post-treatment
NAAT or culture
DGI / septic arthritis
Ceftriaxone 1 g IV daily x 7+ d
Joint drainage if purulent
Endocarditis
Ceftriaxone 1-2 g IV q12-24h x 4 wk
Surgical evaluation
Neonatal ophthalmia
Ceftriaxone 25-50 mg/kg IV/IM x 1
Saline irrigation; admit
Severe beta-lactam allergy
Gentamicin 240 mg IM + azithromycin 2 g PO
Less effective; reserve
CDC 2021 gonorrhea treatment regimens by site and severity.
Treatment
First-line
Uncomplicated urogenital, rectal, or pharyngeal gonorrhea (CDC 2021):
• Ceftriaxone 500 mg IM × 1 (1 g IM if patient weighs ≥150 kg)
• Empiric chlamydia coverage with doxycycline 100 mg PO BID × 7 days IF chlamydia not excluded (azithromycin 1 g PO × 1 if pregnant)
• Mantra: 'Ceftriaxone for gonorrhea + doxycycline for chlamydia'
Disseminated gonococcal infection: ceftriaxone 1 g IV/IM daily × 7+ days; switch to oral therapy after improvement (cefixime if susceptibility confirmed)
Gonococcal arthritis/endocarditis/meningitis: ceftriaxone 1-2 g IV q12-24h × longer course (7-14 days arthritis, 4 weeks endocarditis, 10-14 days meningitis)
Disseminated gonococcal infection: arthritis (purulent or arthralgia-tenosynovitis-dermatitis syndrome), rarely endocarditis or meningitis
Neonatal: ophthalmia neonatorum with risk of corneal perforation and blindness, scalp abscess, sepsis
Increased HIV transmission risk
Antimicrobial resistance threatening current regimens
PANCE pearls
Ceftriaxone dose was DOUBLED to 500 mg IM in CDC 2021 guidelines to combat emerging resistance.
Pharyngeal gonorrhea is hard to eradicate — perform test of cure 7-14 days after treatment.
Always co-treat for chlamydia if not excluded by NAAT — coinfection is common.
DGI: think of complement deficiency (C5-C9) in recurrent disseminated gonococcal infection — order CH50.
Newborn with bilateral purulent conjunctivitis at 2-5 days of life — assume gonococcal until proven otherwise; emergency treatment to prevent corneal perforation.
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