Gonococcal Infections

Gonococcal Infections in Adolescents and Adults

In the United States, an estimated 820,000 new N. gonorrhoeae infections occur each year (533). Gonorrhea is the second most commonly reported communicable disease (118). Urethral infections caused by N. gonorrhoeae among men can produce symptoms that cause them to seek curative treatment soon enough to prevent sequelae, but often not soon enough to prevent transmission to others. Among women, gonococcal infections are commonly asymptomatic or might not produce recognizable symptoms until complications (e.g., PID) have occurred. PID can result in tubal scarring that can lead to infertility and ectopic pregnancy.

Annual screening for N. gonorrhoeae infection is recommended for all sexually active women aged <25 years and for older women at increased risk for infection (e.g., those who have a new sex partner, more than one sex partner, a sex partner with concurrent partners, or a sex partner who has an STI) (108). Additional risk factors for gonorrhea include inconsistent condom use among persons who are not in mutually monogamous relationships, previous or coexisting sexually transmitted infections, and exchanging sex for money or drugs. Clinicians should consider the communities they serve and might opt to consult local public health authorities for guidance on identifying groups at increased risk. Gonococcal infection, in particular, is concentrated in specific geographic locations and communities. Subgroups of MSM are at high risk for gonorrhea infection and should be screened at sites of exposure (see MSM). Screening for gonorrhea in men and older women who are at low risk for infection is not recommended (108). A recent travel history with sexual contacts outside of the United States should be part of any gonorrhea evaluation.

Diagnostic Considerations

Specific microbiologic diagnosis of infection with N. gonorrhoeae should be performed in all persons at risk for or suspected to have gonorrhea; a specific diagnosis can potentially reduce complications, reinfections, and transmission. Culture and NAAT are available for the detection of genitourinary infection with N. gonorrhoeae (394); culture requires endocervical (women) or urethral (men) swab specimens. NAAT allows for the widest variety of FDA-cleared specimen types, including endocervical swabs, vaginal swabs, urethral swabs (men), and urine (from both men and women). However, product inserts for each NAAT manufacturer must be carefully consulted because collection methods and specimen types vary. Culture is available for detection of rectal, oropharyngeal, and conjunctival gonococcal infection, but NAAT is not FDA-cleared for use with these specimens. Some laboratories have met CLIA regulatory requirements and established performance specifications for using NAAT with rectal and oropharyngeal swab specimens that can inform clinical management. Certain NAATs that have been demonstrated to detect commensal Neisseria species might have comparable low specificity when testing oropharyngeal specimens for N gonorrhoeae (394). The sensitivity of NAAT for the detection of N. gonorrhoeae in urogenital and nongenital anatomic sites is superior to culture, but varies by NAAT type (394,505-508). In cases of suspected or documented treatment failure, clinicians should perform both culture and antimicrobial susceptibility testing because nonculture tests cannot provide antimicrobial susceptibility results. Because N. gonorrhoeae has demanding nutritional and environmental growth requirements, optimal recovery rates are achieved when specimens are inoculated directly and when the growth medium is promptly incubated in an increased CO2 environment (394). Several non-nutritive swab transport systems are available that might maintain gonococcal viability for up to 48 hours in ambient temperatures (534-536).

Because of its high specificity (>99%) and sensitivity (>95%), a Gram stain of urethral secretions that demonstrates polymorphonuclear leukocytes with intracellular Gram-negative diplococci can be considered diagnostic for infection with N. gonorrhoeae in symptomatic men. However, because of lower sensitivity, a negative Gram stain should not be considered sufficient for ruling out infection in asymptomatic men. Detection of infection using Gram stain of endocervical, pharyngeal, and rectal specimens also is insufficient and is not recommended. MB/GV stain of urethral secretions is an alternative point-of-care diagnostic test with performance characteristics similar to Gram stain. Presumed gonococcal infection is established by documenting the presence of WBC containing intracellular purple diplococci in MB/GV smears.

NOTE

Updated recommendations for uncomplicated gonorrhea infections in adolescents and adults are found in the MMWR special policy note titled, “Update to CDC’s Treatment Guidelines for Gonococcal Infection, 2020” published in December 2020. Outdated information in this document has been redacted accordingly. Please refer to the MMWR. Updates for the remaining gonorrhea recommendations are forthcoming.

Regimen for uncomplicated gonococcal infections of the cervix, urethra, or rectum:
  • Ceftriaxone 500 mg IM as a single dose for persons weighing <150 kg (300 lb)
    • For persons weighing ≥150 kg (300 lb), 1 g of IM ceftriaxone should be administered.

If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally twice daily for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.

Alternative regimens for uncomplicated gonococcal infections of the cervix, urethra, or rectum if ceftriaxone is not available:
  • Gentamicin 240 mg IM as a single dose plus azithromycin 2 g orally as a single dose
    OR
  • Cefixime 800 mg orally as a single dose. If treating with cefixime, and chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally twice daily for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.
Regimen for uncomplicated gonococcal infections of the pharynx:
  • Ceftriaxone 500 mg IM as a single dose for persons weighing <150 kg (300 lb)
    • For persons weighing ≥150 kg (300 lb), 1 g of IM ceftriaxone should be administered.

If chlamydia coinfection is identified when pharyngeal gonorrhea testing is performed, providers should treat for chlamydia with doxycycline 100 mg orally twice a day for 7 days. During pregnancy, azithromycin 1 g as a single dose is recommended to treat chlamydia.

No reliable alternative treatments are available for pharyngeal gonorrhea. For persons with a history of a beta-lactam allergy, a thorough assessment of the reaction is recommended. For more information, see Management of Persons Who Have a History of Penicillin Allergy in the 2015 STD Treatment Guidelines.

For persons with an anaphylactic or other severe reaction (e.g., Steven’s Johnson syndrome) to ceftriaxone, consult an infectious disease specialist for an alternative treatment.

Follow-Up

A test-of-cure is not needed for persons who receive a diagnosis of uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens; however, any person with pharyngeal gonorrhea who is treated with any regimen should return 714 days after treatment for a test-of cure using either culture or NAAT. All positive cultures for test-of-cure should undergo antimicrobial susceptibility testing.

Symptoms that persist after treatment should be evaluated by culture for N. gonorrhoeae (with or without simultaneous NAAT), and any gonococci isolated should be tested for antimicrobial susceptibility. Persistent urethritis, cervicitis, or proctitis also might be caused by other organisms (see Urethritis, Cervicitis, and Proctitis sections).

A high prevalence of N. gonorrhoeae infection has been observed among men and women previously treated for gonorrhea (86,480,481,577). Rather than signaling treatment failure, most of these infections result from reinfection caused by failure of sex partners to receive treatment or the initiation of sexual activity with a new infected partner, indicating a need for improved patient education and treatment of sex partners. Men or women who have been treated for gonorrhea should be retested 3 months after treatment regardless of whether they believe their sex partners were treated. If retesting at 3 months is not possible, clinicians should retest whenever persons next present for medical care within 12 months following initial treatment.

Special Considerations

Allergy, Intolerance, and Adverse Reactions

Allergic reactions to first-generation cephalosporins occur in <2.5% of persons with a history of penicillin allergy and are uncommon with third-generation cephalosporins (e.g., ceftriaxone and cefixime) (428,430,464). Use of ceftriaxone or cefixime is contraindicated in persons with a history of an IgE-mediated penicillin allergy (e.g., anaphylaxis, Stevens Johnson syndrome, and toxic epidermal necrolysis) (428,431). Data are limited regarding alternative regimens for treating gonorrhea among persons who have either a cephalosporin or IgE-mediated penicillin allergy. A potential therapeutic option is dual treatment with intramuscular gentamicin 240 mg plus oral azithromycin 2 g (569). Spectinomycin for treatment of urogenital and anorectal gonorrhea can be considered when available. Providers treating persons with cephalosporin or IgE-mediated penicillin allergy should consult an infectious-disease specialist.

HIV Infection

Persons who have gonorrhea and HIV infection should receive the same treatment regimen as those who are HIV negative. For more information, see appropriate treatment sections under Gonoccocal Infections.

Suspected Cephalosporin Treatment Failure

Cephalosporin treatment failure is the persistence of N. gonorrhoeae infection despite appropriate cephalosporin treatment and is indicative of infection with cephalosporin-resistant gonorrhea in persons whose partners were adequately treated and whose risk for reinfection is low. Suspected treatment failure has been reported among persons receiving oral and injectable cephalosporins (541-557,578). Treatment failure should be considered in 1) persons whose symptoms do not resolve within 3–5 days after appropriate treatment and report no sexual contact during the post-treatment follow-up period and 2) persons with a positive test-of-cure (i.e., positive culture >72 hours or positive NAAT ≥7 days after receiving recommended treatment) when no sexual contact is reported during the post-treatment follow-up period (579). Treatment failure should also be considered in persons who have a positive culture on test-of-cure (if obtained) if there is evidence of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the post-treatment follow-up period.

Most suspected treatment failures in the United States are likely to be re-infections rather than actual treatment failures (86,480,481,577). However, in cases where reinfection is unlikely and treatment failure is suspected, before retreatment, relevant clinical specimens should be obtained for culture (preferably with simultaneous NAAT) and antimicrobial susceptibility testing if N. gonorrhoeae is isolated. Phenotypic antimicrobial susceptibility testing should be performed using disk diffusion, Etest (BioMérieux, Durham, NC), or agar dilution. Data are limited on the use of DNA amplification and sequencing for detection of genetic mutations associated with gonococcal antimicrobial resistance. All isolates of suspected treatment failures should be sent to CDC for antimicrobial susceptibility testing by agar dilution; local laboratories should store isolates for possible further testing if needed. Testing and/or storage of specimens or isolates should be facilitated by the state or local health department according to local public health protocol. Instructions for shipping isolates to CDC are available at www.cdc.gov/std/gonorrhea/arg/specimen_shipping_instructions1-29-08.pdfpdf icon.

For persons with suspected cephalosporin treatment failure, the treating clinician should consult an infectious-disease specialist, an STD/HIV Prevention Training Center clinical expert (http://www.nnptc.orgexternal icon), the local or state health department STD program, or CDC (telephone: 404-718-5447) for advice on obtaining cultures, antimicrobial susceptibility testing, and treatment. Suspected treatment failure should be reported to CDC through the local or state health department within 24 hours of diagnosis.

Suspected treatment failures first should be retreated routinely with the recommended regimen, because reinfections are more likely than actual treatment failures. However, in situations with a higher likelihood of treatment failure than reinfection, relevant clinical specimens should be obtained for culture (preferably with simultaneous NAAT) and antimicrobial susceptibility testing performed before retreatment. Dual treatment with single doses of intramuscular gentamicin 240 mg plus oral azithromycin 2 g can be considered, particularly when isolates are found to have elevated cephalosporin MICs (569). A test-of-cure at relevant clinical sites should be obtained 7–14 days after retreatment; culture is the recommended test, preferably with simultaneous NAAT and antimicrobial susceptibility testing of N gonorrhoeae if isolated. Clinicians should ensure that the patient’s sex partners from the preceding 60 days are evaluated promptly with culture and presumptively treated using the same regimen used for the patient.

Gonococcal Conjunctivitis

In the only published study (conducted in 1989) of the treatment of gonococcal conjunctivitis among adults, all 12 study participants responded to a single 1-g IM injection of ceftriaxone (580). On the basis of experience with other microbes that have developed antimicrobial resistance rapidly, a theoretical basis exists for combination therapy using two antimicrobials with different mechanisms of action (e.g., a cephalosporin plus azithromycin) to improve treatment efficacy and potentially slow the emergence and spread of resistance to cephalosporins. Because gonococcal conjunctivitis is uncommon and data on treatment of gonococcal conjunctivitis in adults are limited, consultation with an infectious-disease specialist should be considered.

Recommended Regimen
  • Ceftriaxone 1 g IM in a single dose
    PLUS
  • Azithromycin 1 g orally in a single dose

Consider one-time lavage of the infected eye with saline solution.

Management of Sex Partners

Patients should be instructed to refer their sex partners for evaluation and treatment. For more information, see Gonococcal Infections, Management of Sex Partners.

Disseminated Gonococcal Infection

Disseminated gonococcal infection (DGI) frequently results in petechial or pustular acral skin lesions, asymmetric polyarthralgia, tenosynovitis, or oligoarticular septic arthritis (581). The infection is complicated occasionally by perihepatitis and rarely by endocarditis or meningitis. Some strains of N. gonorrhoeae that cause DGI can cause minimal genital inflammation. If DGI is suspected, NAAT or culture specimens from urogenital and extragenital sites, as applicable, should be collected and processed in addition to specimens from disseminated sites of infection (e.g., skin, synovial fluid, blood, and the CNS). All N. gonorrhoeae isolates should be tested for antimicrobial susceptibility.

Hospitalization and consultation with an infectious-disease specialist are recommended for initial therapy, especially for persons who might not comply with treatment, have an uncertain diagnosis, or have purulent synovial effusions or other complications. Examination for clinical evidence of endocarditis and meningitis should be performed.

Treatment of Arthritis and Arthritis-Dermatitis Syndrome
Recommended Regimen
  • Ceftriaxone 1 g IM or IV every 24 hours
    PLUS
  • Azithromycin 1 g orally in a single dose
Alternative Regimens
  • Cefotaxime 1 g IV every 8 hours
    OR
  • Ceftizoxime 1 g IV every 8 hours
    PLUS
  • Azithromycin 1 g orally in a single dose

When treating for the arthritis-dermatitis syndrome, the provider can switch to an oral agent guided by antimicrobial susceptibility testing 24–48 hours after substantial clinical improvement, for a total treatment course of at least 7 days.

Treatment of Gonococcal Meningitis and Endocarditis
Recommended Regimen
  • Ceftriaxone 1–2 g IV every 12–24 hours
    PLUS
  • Azithromycin 1 g orally in a single dose

No recent studies have been published on the treatment of DGI. The duration of treatment of DGI has not been systematically studied and should be determined in consultation with an infectious-disease specialist. Treatment for DGI should be guided by the results of antimicrobial susceptibility testing. Pending antimicrobial susceptibility results, treatment decisions should be made on the basis of clinical presentation. Therapy for meningitis should be continued with recommended parenteral therapy for 10–14 days. Parenteral antimicrobial therapy for endocarditis should be administered for at least 4 weeks.

Management of Sex Partners

Gonococcal infection frequently is asymptomatic in sex partners of persons who have DGI. Providers should instruct patients to refer partners with whom they have had sexual contact in the past 60 days for evaluation, testing, and presumptive treatment (see Gonococcal Infection, Management of Sex Partners).

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Gonococcal Infections Among Neonates

Prenatal screening and treatment of pregnant women is the best method for preventing GC infection among neonates. Gonococcal infection among neonates results from perinatal exposure to the mother’s infected cervix. It is usually an acute illness that manifests 2–5 days after birth. The prevalence of infection among infants depends on the prevalence of infection among pregnant women, whether pregnant women are screened and treated for gonorrhea, and whether newborns receive ophthalmia prophylaxis. The most severe manifestations of N. gonorrhoeae infection in newborns are ophthalmia neonatorum and sepsis, which can include arthritis and meningitis. Less severe manifestations include rhinitis, vaginitis, urethritis, and infection at sites of fetal monitoring.

Ophthalmia Neonatorum Prophylaxis

To prevent gonococcal ophthalmia neonatorum, a prophylactic agent should be instilled into both eyes of all newborn infants; this procedure is required by law in most states. Ocular prophylaxis is warranted because it can prevent sight-threatening gonococcal ophthalmia, has an excellent safety record, is easy to administer, and is inexpensive. The recommended prophylactic regimen prevents gonococcal ophthalmia; however, its efficacy for prevention of chlamydial ophthalmia is less clear, and it does not eliminate nasopharyngeal colonization by C. trachomatis.

Recommended Regimen
  • Erythromycin (0.5%) ophthalmic ointment in each eye in a single application at birth

This preparation should be instilled into both eyes of all neonates as soon as possible after delivery, regardless of whether they are delivered vaginally or by cesarean section. Ideally, ointment should be applied using single-use tubes or ampules rather than multiple-use tubes. If prophylaxis is delayed (i.e., not administered in the delivery room), a monitoring system should be established to ensure that all infants receive prophylaxis.

Erythromycin is the only antibiotic ointment recommended for use in neonates. Silver nitrate and tetracycline ophthalmic ointment is no longer manufactured in the United States, bacitracin is not effective, and povidone iodine has not been studied adequately (582,583). Gentamicin ophthalmic ointment has been associated with severe ocular reactions in neonates and should not be used for ocular prophylaxis (584,585). If erythromycin ointment is not available, infants at risk for exposure to N. gonorrhoeae (especially those born to a mother at risk for gonococcal infection or with no prenatal care) can be administered ceftriaxone 25–50 mg/kg IV or IM, not to exceed 125 mg in a single dose (586).

N. gonorrhoeae causes ophthalmia neonatorum relatively infrequently in the United States (587). However, identifying and treating this infection is especially important, because ophthalmia neonatorum can result in perforation of the globe of the eye and blindness (588).

Diagnostic Considerations

Infants at increased risk for gonococcal ophthalmia include those who did not receive ophthalmia prophylaxis and whose mothers had no prenatal care or have a history of STDs or substance abuse. Gonococcal ophthalmia is strongly suspected when intracellular gram-negative diplococci are identified on Gram stain of conjunctival exudate, justifying presumptive treatment for gonorrhea after appropriate cultures and antimicrobial susceptibility testing for N. gonorrhoeae are performed. Presumptive treatment for N. gonorrhoeae might be indicated for newborns at increased risk for gonococcal ophthalmia who have increased WBCs (but not intracellular gram negative diplococci) in a Gram-stained smear of conjunctival exudate. Nongonococcal causes of neonatal ophthalmia include Moraxella catarrhalis and other Neisseria species, organisms that are indistinguishable from N. gonorrhoeae on Gram-stained smear but can be differentiated in the microbiology laboratory.

Treatment

Recommended Regimen
  • Ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg

One dose of ceftriaxone is adequate therapy for gonococcal conjunctivitis. Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely. No data exist on the use of dual therapy for the treatment of gonococcal ophthalmia. Topical antibiotic therapy alone is inadequate and unnecessary if systemic treatment is administered.

Other Management Considerations

Appropriate chlamydial testing should be done simultaneously from the inverted eyelid specimen (see Ophthalmia Neonatorum Caused by C. trachomatis). Infants who have gonococcal ophthalmia should be evaluated for signs of disseminated infection (e.g., sepsis, arthritis, and meningitis). Infants who have gonococcal ophthalmia should be managed in consultation with an infectious-disease specialist.

Follow-up

Infants who have ophthalmia neonatorum should be managed in consultation with an infectious-disease specialist.

Management of Mothers and Their Sex Partners

Mothers of infants with ophthalmia neonatorum caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s). For more information, see Gonococcal Infections in Adolescents and Adults.

DGI and Gonococcal Scalp Abscesses in Neonates

DGI might present as sepsis, arthritis, or meningitis and is a rare complication of neonatal gonococcal infection. Localized gonococcal infection of the scalp can result from fetal monitoring through scalp electrodes. Detection of gonococcal infection in neonates who have sepsis, arthritis, meningitis, or scalp abscesses requires cultures of blood, CSF, and joint aspirate. Specimens obtained from the conjunctiva, vagina, oropharynx, and rectum are useful for identifying the primary site(s) of infection. Antimicrobial susceptibility testing of all isolates should be performed. Positive Gram-stained smears of exudate, CSF, or joint aspirate provide a presumptive basis for initiating treatment for N. gonorrhoeae.

Recommended Regimens
  • Ceftriaxone 25–50 mg/kg/day IV or IM in a single daily dose for 7 days, with a duration of 10–14 days if meningitis is documented
    OR
  • Cefotaxime 25 mg/kg IV or IM every 12 hours for 7 days, with a duration of 10–14 days if meningitis is documented

Ceftriaxone should be administered cautiously to hyperbilirubinemic infants, especially those born prematurely. No data exist on the use of dual therapy for the treatment of DGI or gonococcal scalp abscesses.

Other Management Considerations

Appropriate chlamydial testing should be done simultaneously in neonates with gonococcal infection. For more information, see Chlamydia Infection in Neonates. Infants who have DGI should be managed in consultation with an infectious-disease specialist.

Management of Mothers and Their Sex Partners

Mothers of infants who have DGI or scalp abscesses caused by N. gonorrhoeae should be evaluated, tested, and presumptively treated for gonorrhea, along with their sex partner(s). For more information, see Gonococcal Infections in Adolescents and Adults.

Neonates Born to Mothers Who Have Gonococcal Infection

Neonates born to mothers who have untreated gonorrhea are at high risk for infection. Neonates should be tested for gonorrhea at exposed sites and treated presumptively for gonorrhea as recommended in these guidelines. No data exist on the use of dual therapy to treat neonates born to mothers who have gonococcal infection.

Recommended Regimen in the Absence of Signs of Gonococcal Infection
  • Ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg
Other Management Considerations

Appropriate chlamydial testing should be done simultaneously in neonates with gonococcal infection. For more information, see Chlamydia Infection in Neonates. Follow-up examination is not required.

Management of Mothers and Their Sex Partners

Mothers who have gonorrhea and their sex partners should be evaluated, tested, and presumptively treated for gonorrhea. For more information, see Gonococcal Infections.

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Gonococcal Infections Among Infants and Children

Sexual abuse is the most frequent cause of gonococcal infection in infants and children (see Sexual Assault or Abuse of Children). For preadolescent girls, vaginitis is the most common manifestation of this infection; gonococcal-associated PID after vaginal infection can be less common in preadolescents than adults. Among sexually abused children, anorectal and pharyngeal infections with N. gonorrhoeae are frequently asymptomatic.

Diagnostic Considerations

NAAT can be used to test vaginal and urine specimens from girls (see Sexual Assault or Abuse of Children), although data are insufficient to recommend the use of these tests in boys and from extragenital sites (rectum and pharynx) in boys and girls (394). Culture remains the preferred method for diagnosing boys and for detecting infection in specimens obtained from extragenital sites regardless of gender (394). Gram stains are inadequate for evaluating prepubertal children for gonorrhea and should not be used to diagnose or exclude gonorrhea. If evidence of disseminated gonococcal infection exists, gonorrhea culture and antimicrobial susceptibility testing should be obtained from relevant clinical sites (see DGI).

Recommended Regimen for Infants and Children Who Weigh ≤45 kg and Who Have Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis
  • Ceftriaxone 25–50 mg/kg IV or IM in a single dose, not to exceed 125 mg IM
Recommended Regimen for Children Who Weigh >45 kg and Who Have Uncomplicated Gonococcal Vulvovaginitis, Cervicitis, Urethritis, Pharyngitis, or Proctitis
  • Treat with one of the regimens recommended for adults (see Gonococcal Infections)
Recommended Regimen for Children Who Weigh ≤45 kg and Who Have Bacteremia or Arthritis
  • Ceftriaxone 50 mg/kg (maximum dose: 1 g) IM or IV in a single dose daily for 7 days
Recommended Regimen for Children Who Weigh >45 kg and Who Have Bacteremia or Arthritis
  • Ceftriaxone 1 g IM or IV in a single dose daily every 24 hours for 7 days

No data exist regarding the use of dual therapy for treating children with gonococcal infection.

Other Management Considerations

Follow-up cultures are unnecessary. Only parenteral cephalosporins (i.e., ceftriaxone) are recommended for use in children. All children found to have gonococcal infections should be tested for C. trachomatis, syphilis, and HIV. For a discussion of concerns regarding sexual assault, see Sexual Assault or Abuse of Children.

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