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
About 650,000 reported 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.
Try two board-style Gonorrhea questions
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Question 1RenalMedium
A 24-year-old sexually active man presents with dysuria and yellow urethral discharge for 3 days. Gram stain of the discharge reveals gram-negative intracellular diplococci. He is treated with intramuscular ceftriaxone and oral doxycycline. He returns 2 weeks later with right scrotal pain and swelling. Which of the following is the most likely complication of his initial infection?
AEpididymitis
BIsolated orchitis
CAcute prostatitis
DFournier gangrene
EProstate abscess
Reveal answer & full explanation
Correct answer: A — Epididymitis
AEpididymitis✓
BIsolated orchitis
CAcute prostatitis
DFournier gangrene
EProstate abscess
Why Epididymitis is correct
This patient had gonococcal urethritis; the most common local complication in young sexually active men is acute epididymitis from retrograde ascent of organisms through the vas deferens.
Untreated or partially treated urethritis from Neisseria gonorrhoeae or Chlamydia trachomatis can extend up the genital tract, producing unilateral scrotal pain, swelling, and tenderness consistent with this presentation.
Epididymitis is by far the most frequent complication of sexually transmitted urethritis in men under 35.
Why the others are wrong
Isolated orchitis — orchitis without epididymal involvement is uncommon and usually viral (classically mumps); bacterial orchitis almost always arises by contiguous spread from the epididymis, so ascending gonococcal or chlamydial infection causes epididymitis or epididymo-orchitis rather than isolated orchitis (confused-with adjacent structure).
Fournier gangrene — a rare necrotizing fasciitis of the perineum seen in immunocompromised or diabetic patients, not a typical urethritis sequela (anchoring on rare complication).
Prostate abscess — rare and typically occurs in older men or those with diabetes or instrumentation rather than as a routine complication of urethritis (premature closure).
Acute prostatitis — urethral infection can ascend to the prostate, but acute bacterial prostatitis typically causes fever, perineal or low back pain, and voiding symptoms with a tender prostate rather than unilateral scrotal pain and swelling, and it is much less common than epididymitis in young men (confused-with ascending infection site).
Question 2Infectious DiseaseMedium
A 23-year-old man has urethral discharge. NAAT confirms Neisseria gonorrhoeae. Which of the following is the most appropriate treatment?
AIntramuscular ceftriaxone dose
BOral cefixime single dose
COral azithromycin single dose
DIntramuscular penicillin G dose
EOral ciprofloxacin single dose
Reveal answer & full explanation
Correct answer: A — Intramuscular ceftriaxone dose
AIntramuscular ceftriaxone dose✓
BOral cefixime single dose
COral azithromycin single dose
DIntramuscular penicillin G dose
EOral 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
Intramuscular penicillin G dose — Penicillin was abandoned for gonorrhea because of penicillinase-producing and chromosomally resistant strains; IM benzathine penicillin G is the syphilis regimen and will not reliably cure this infection.
Oral cefixime single dose — Oral cefixime is only a backup when ceftriaxone is unavailable; it achieves lower tissue levels and is not first-line.
Oral ciprofloxacin single dose — Fluoroquinolones were dropped for gonorrhea because of widespread resistance; using ciprofloxacin risks treatment failure.
Oral azithromycin single dose — azithromycin was once paired with ceftriaxone for gonorrhea, but rising macrolide resistance means it is no longer used alone; even the 2-g dose is reserved for pairing with gentamicin when ceftriaxone cannot be given.
Additional high-yield points
Azithromycin is no longer used alone for gonorrhea because of rising macrolide resistance; a 2-g dose is paired with gentamicin 240 mg IM only as an alternative when ceftriaxone cannot be given.
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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%; risk factors include female sex, menstruation, pregnancy, and terminal complement (C5-C9) deficiency, which should be sought in recurrent DGI.
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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