Gonorrhea

Gonorrhea is a sexually transmitted infection caused by the bacterium Neisseria gonorrhoeae. The infection most commonly affects individuals between 15–24 years of age and has an incubation period of 2–8 days. Gonorrhea is commonly asymptomatic, especially in individuals with female genitalia, which increases the risk of spread and complications. Genitourinary (GU) symptoms include purulent urethral or vaginal discharge and dysuria; affected individuals may also present with signs of epididymitis or pelvic inflammatory disease (PID). Gonorrhea can cause extragenital infections, such as proctitis, conjunctivitis, and pharyngitis. Rarely, disseminated gonococcal infection occurs and typically manifests with a triad of arthralgia, dermatitis, and tenosynovitis. Diagnosis of gonorrhea is usually made with a nucleic acid amplification test (NAAT) and/or culture of affected sites. Management consists of antibiotic therapy for gonorrhea, identification and management of coinfections, and treatment of sexual partners. Untreated infection may lead to complications such as urethral strictures, infertility in those with female genitalia, and vertical transmission. Patient education on the prevention of STIs and regular screening of at-risk individuals can mitigate transmission.

• Incidence ^[1][2]
  • Second most commonly reported infectious disease in the US after Chlamydia
  • ∼ 820,000 cases per year in the US
• Age: primarily individuals between 15–24 years of age

Epidemiological data refers to the US, unless otherwise specified.

• Pathogen
  • Neisseria gonorrhoeae (N. gonorrhoeae, gonococcus)
  • Gram-negative, intracellular, aerobic, diplococci
  • The incubation time is typically 2–8 days.
• Transmission
  • Sexual (oral, genital, or anal)
  • Perinatal
• Risk factors (see “Risk factors for STIs”)
  • High-risk sexual behaviors (lack of barrier protection, multiple partners)
  • Asplenia, complement deficiencies
• Risk groups
  • Men who have sex with men (MSM)
  • Individuals with low socioeconomic status

Uncomplicated GU gonococcal infections

• Gonococcal urethritis
  • Mucopurulent urethral discharge (yellow-green, possibly blood-tinged)
  • Dysuria
  • ↑ Urinary frequency
  • Individuals with female genitalia are often asymptomatic; can be associated with:
    • Bartholin gland abscess: pain, edema, and discharge on the labia ^[3]
    • Vulvovaginitis (rare) ^[4][5]
  • Individuals with male genitalia may have penile shaft edema and/or prostatitis.
• Gonococcal cervicitis
  • May be asymptomatic
  • Mucopurulent, yellow, malodorous cervical or vaginal discharge
  • Pelvic examination: cervical erythema and, upon manipulation, cervical pain and bleeding (i.e., friable cervix) ^[5]
  • Postcoital or intermenstrual bleeding

Complicated GU gonococcal infections

• Gonococcal pelvic inflammatory disease (PID)
  • Fever, abdominal pain, pelvic pain and/or dyspareunia
  • Abnormal intermenstrual bleeding or menorrhagia
  • Abnormal vaginal discharge (yellow/green color)
  • May progress to Fitz-Hugh-Curtis syndrome, e.g., RUQ pain due to perihepatitis
  • See also “Clinical features of PID.”
• Epididymitis and/or orchitis ^[6][7]
  • Orchitis: enlarged, swollen, tender testicles
  • Epididymitis: typically one-sided scrotal pain and swelling ^[6]

Scrotal pain and swelling indicate a complicated genitourinary infection.

Extragenital gonococcal infections ^[8]

• Gonococcal conjunctivitis
  • Affects newborns (vertical transmission) and sexually active individuals
  • Manifests as hyperacute conjunctivitis
  • See “Gonococcal conjunctivitis” and “Neonatal gonococcal conjunctivitis.”
• Gonococcal pharyngitis
  • Occurs via oral-genital contact
  • May be asymptomatic
  • Sore throat
  • Pharyngeal exudate
  • Cervical lymphadenitis
• Gonococcal proctitis
  • Occurs via receptive anal intercourse or spread from adjacent genitourinary sites ^[5][8]
  • May be asymptomatic
  • Purulent discharge
  • Anorectal bleeding and pain
  • Rectal mucosa inflammation
  • Perianal abscess (uncommon) ^[9]
  • Constipation
  • Tenesmus

Gonococcal urethritis is usually symptomatic in individuals with male genitalia. ^[10]

Gonococcal infections of the pharynx, rectum, and female genitalia are frequently asymptomatic. ^[8]

Invasive gonococcal infections

• See “Clinical features of DGI.”

Multiple medical organizations recommend screening for asymptomatic individuals who are at increased risk for gonorrhea infection and its complications. ^[8][11][12]

• NAAT is recommended for screening.
• Screening for chlamydia is typically performed concurrently using the same specimen.
• If screening is positive, see “Management of gonorrhea” and screen for other STIs (e.g., chlamydia, syphilis, HIV).

Best practices for screening transgender individuals have not been established; screening methods should be individualized based on the patient's anatomy. See also “Principles of transgender health care.” ^[8][13]

Patients can self-swab for gonorrhea screening. ^[8]

NAAT and/or culture are most commonly used to diagnose gonorrhea; gram stain can be used as an alternative in individuals with male genitalia who present with symptomatic urethritis). Chlamydia testing is typically performed concurrently using the same specimen. For individuals with disseminated gonococcal infection, see “Diagnostics of DGI” for additional studies. ^[8]

NAAT ^[8][13][14]

• Indication: NAAT is the preferred test for diagnosis and screening due to higher sensitivity compared to culture.
• Specimen collection: swab of an affected site (e.g., urethra, endocervix, rectum, conjunctiva, pharynx) OR first-void urine ^[15]
• For urogenital infections, first-void urine is preferred in individuals with male genitalia, and a vaginal swab is preferred in individuals with female genitalia.
• Point-of-care testing is available for rapid results.

With proper instruction, patients may collect their own NAAT samples using first-void urine or swabs of the vagina, rectum, and/or oropharynx.

Gram stain ^[8][13][14]

• Indication: can be used in place of NAAT for individuals with male genitalia who present with symptomatic urethritis
• Specimen collection: swab of urethral discharge or secretions
• Findings: polymorphonuclear leukocytes and intracellular gram-negative diplococci

N. meningitidis and N. gonorrhoeae are often indistinguishable when evaluated with gram stain. If the gram stain is positive and NAAT is negative, suspect N. meningitidis and obtain a culture for confirmation. ^[8]

Culture ^[8][14]

Cultures are typically performed in combination with NAAT, and results take ∼ 48 hours.

• Indications
  • NAAT is unavailable ^[14]
  • For antibiotic sensitivity testing, e.g., treatment failure, severe or complicated infections, such as PID and DGI
  • Diagnosis in children (under the guidance of a child abuse specialist) ^[8][16]
• Specimen collection: swab of an affected site
• Method: The swab is plated on Thayer-Martin agar.

Approach ^[8][13]

All patients with suspected or confirmed gonorrhea should receive the following recommendations. Additional treatment for DGI may be required.

• Administer antibiotic therapy for gonorrhea; directly observed therapy is recommended.
• Provide antibiotics to the most recent sexual partner and all partners from the preceding 60 days (see “ STI management of sexual partners”). ; ^[8][17]
  • Preferred treatment: ceftriaxone IM
  • Alternative: expedited partner therapy with cefixime
• Instruct the patient to avoid all sexual contact until
  • 7 days after treatment of the patient and their sexual partners
  • Symptoms have resolved
• Offer to screen for other STIs, evaluate for pregnancy, and prescribe or refer for contraception.
• Counsel on gonorrhea prevention and STI prevention. ^[8]
• Arrange for appropriate follow-up.

Ensure all cases of gonorrhea are reported to the local health department. ^[18]

Antibiotic therapy for gonorrhea ^[8][13][17]

• Uncomplicated GU and extragenital infections: Ceftriaxone (single IM dose) is the first-line treatment.
• Complicated GU infections: Ceftriaxone is combined with additional antibiotics (e.g., doxycycline± metronidazole). ^[8]
• Disseminated gonococcal infections: Prolonged courses of ceftriaxone IV are given.
• All patients: If coinfection with Chlamydia trachomatis has not been excluded, provide additional treatment for genitourinary chlamydia.
  • Nonpregnant individuals: doxycycline
  • Pregnant individuals: azithromycin ^[8]

Sexual partners must be treated simultaneously to avoid reinfections.

Pregnant patients can be safely treated with ceftriaxone; for patients with cephalosporin allergy, consult infectious diseases. ^[8]

Follow-up ^[8][13]

• Resolution of symptoms
  • Test-of-cure: not needed for most patients; obtain for pharyngeal gonorrhea 7–14 days after treatment
  • All patients: Retest at 3 months.
  • Pregnant individuals: Retest during the 3^rd trimester if ongoing risk factors are present (see “Prenatal screening for gonorrhea”).
• Persistent symptoms 3–5 days after treatment or positive repeat testing ^[8][19]
  • Ensure the patient and partners have been treated; most suspected treatment failures are reinfections.
  • Obtain both NAAT and culture with antibiotic sensitivity testing (see “Diagnostics for gonorrhea”).
  • Repeat treatment
    • Suspected reinfection or an alternative treatment regimen was used: Administer ceftriaxone.
    • Suspected cephalosporin resistance: Contact infectious diseases and consider gentamicin PLUS azithromycin .
  • Individualize treatment based on antibiotic sensitivity testing.
  • Obtain a test-of-cure with NAAT and culture 7–14 days after retreatment. ^[8]

A test-of-cure is not indicated for most patients whose symptoms resolve with appropriate treatment. ^[8]

• Hymenal and tubal synechiae, tubal motility disorders → female infertility
• Gonococcal conjunctivitis (particularly in neonates, see “Neisserial conjunctivitis”)
• Disseminated gonococcal infection and its associated complications, e.g., sepsis with endocarditis, meningitis, osteomyelitis, or pneumonia

We list the most important complications. The selection is not exhaustive.

Epidemiology

• Occurs in < 2% of individuals with gonorrhea ^[20][21][22]
• Traditionally, more common in individuals < 40 years of age and female individuals ^[21][22]
• Immunocompromised individuals appear to be at increased risk. ^[8][23]

Etiology

• Hematogenous spread of N. gonorrhoeae from an untreated mucosal gonococcal infection ^[24]

Clinical features of DGI ^[13]

DGI typically manifests as gonococcal arthritis without symptoms of a localized mucosal infection. ^[25]

• Arthritis-dermatitis syndrome
  • Polyarthralgias: migratory, asymmetric arthritis that can become purulent ^[8][25]
  • Tenosynovitis: simultaneous inflammation of several tendons (e.g., in the fingers, toes, wrists, ankles) ^[25]
  • Dermatitis
    • Vesicular, pustular, or maculopapular lesions, possibly with a necrotic or hemorrhagic center ^[26]
    • Distribution: acral (i.e., the extensor surfaces of the hands and feet, sometimes involving the palms and soles), the trunk ^[25][27]
    • Typically < 10 lesions that resolve within 3–4 days ^[25][28]
  • Additional manifestations: fever and chills (especially in the acute phase) ^[25][27]
• Purulent gonococcal arthritis ^[5][29]
  • Abrupt monoarticular or oligoarticular inflammation
  • Commonly affects knees, ankles, elbows, and wrists ^[25][30]
  • Skin manifestations and tenosynovitis are typically absent. ^[25]
• Complications ^[8][25]
  • Bacterial meningitis (gonococcal meningitis)
  • Infective endocarditis (gonococcal endocarditis)
  • Perihepatitis due to PID

Do not confuse gonococcal arthritis with reactive arthritis. See “Differential diagnoses of infection-associated arthritis.”

Diagnostics of DGI ^[8]

• All patients: : Obtain NAAT and culture with antibiotic sensitivity testing from
  • All sites of exposure ^[24]
  • Blood ^[5]
• Patients with gonococcal arthritis: synovial fluid analysis
  • Aspirate: clear (nonpurulent) or cloudy (purulent)
  • Gram stain: positive in < 25–50% of cases ^[26][31]
  • ↑ Leukocyte count
    • Purulent arthritis: 50,000–100,000 cells/mm³ with ↑ segmented neutrophils
    • Nonpurulent arthritis: < 20,000 cells/mm^{3 [26]}
• Patients with meningismus: CSF analysis
• Patients with skin lesions: NAAT and culture of lesions

Cultures taken from sites of dissemination are often negative. Obtain cultures from all sites of exposure even if signs of a localized mucosal infection are absent. ^[24]

Treatment of DGI ^[8]

• All patients
  • Evaluate for signs of sepsis and start management of sepsis if required.
  • Admit patients with DGI to the hospital for initial management.
  • Initiate antibiotics for gonorrhea.
  • If chlamydia coinfection has not been excluded, also provide treatment for genitourinary chlamydia.
  • Consult infectious diseases and other specialists (e.g., orthopedics, cardiology) as needed.
  • See “Management of gonorrhea” for additional information.
• Additional management
  • Purulent gonococcal arthritis: therapeutic arthrocentesis of affected joints; see “Treatment of septic arthritis” for additional management.
  • Gonococcal meningitis: See “Supportive treatment of meningitis” for additional management.
  • Gonococcal endocarditis: See “Management of infectious endocarditis' for additional management.

Prevention of GU gonococcal infections ^[8]

• All sexually active patients
  • Discuss condom use and additional STI prevention.
  • Recommend STI screening for sexually active patients and their sexual partners. ^[32][33]
• In patients who have experienced sexual assault, provide antibiotic prophylaxis for gonococcal infections (see “Management of recent sexual violence”).
• The meningococcal B vaccine, if otherwise indicated, may provide some protection against gonorrhea. ^[14][34][35]
• Offer doxycycline postexposure prophylaxis to MSM and transgender women with ≥ 1 bacterial STI in the past 12 months (see “Postexposure prophylaxis for STIs”). ^[36]

Prevention of neonatal gonococcal infections ^[8]

• In pregnant individuals
  • Provide prenatal screening for gonorrhea.
  • Promptly initiate treatment of gonorrhea infections.
• In newborns: Provide routine neonatal ophthalmic antibiotic prophylaxis at birth.
• See “Prevention of neonatal conjunctivitis.”

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