Gonococcal Infections Among Adolescents and Adults

In the United States, an estimated 1,568,000 new N. gonorrhoeae infections occur each year (141,838), and gonorrhea is the second most commonly reported bacterial communicable disease. Urethral infections caused by N. gonorrhoeae can produce symptoms among men 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 or 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 aged ≥25 years 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) (149). Additional risk factors for gonorrhea include inconsistent condom use among persons who are not in mutually monogamous relationships, previous or coexisting STIs, and exchanging sex for money or drugs. Clinicians should consider the communities they serve and consult local public health authorities for guidance regarding identifying groups at increased risk. Gonococcal infection, in particular, is concentrated in specific geographic locations and communities. MSM at high risk for gonococcal infection (e.g., those with multiple anonymous partners or substance abuse) or those at risk for HIV acquisition should be screened at all anatomic sites of exposure every 3–6 months (see Men Who Have Sex with Men). At least annual screening is recommended for all MSM. Screening for gonorrhea among heterosexual men and women aged >25 years who are at low risk for infection is not recommended (149). A recent travel history with sexual contacts outside the United States should be part of any gonorrhea evaluation.

Diagnostic Considerations

Specific microbiologic diagnosis of N. gonorrhoeae infection should be performed for all persons at risk for or suspected of having gonorrhea; a specific diagnosis can potentially reduce complications, reinfections, and transmission. Culture, NAAT, and POC NAAT, such as GeneXpert (Cepheid), are available for detecting genitourinary infection with N. gonorrhoeae (149); culture requires endocervical (women) or urethral (men) swab specimens. Culture is also available for detecting rectal, oropharyngeal, and conjunctival gonococcal infection. NAATs and POC NAATs allow for the widest variety of FDA-cleared specimen types, including endocervical and vaginal swabs and urine for women, urethral swabs and urine for men, and rectal swabs and pharyngeal swabs for men and women (www.accessdata.fda.gov/cdrh_docs/reviews/K121710.pdfpdf iconexternal icon). However, product inserts for each NAAT manufacturer should be consulted carefully because collection methods and specimen types vary. Certain NAATs that have been demonstrated to detect commensal Neisseria species might have comparable low specificity when testing oropharyngeal specimens for N. gonorrhoeae (553). NAAT sensitivity for detecting N. gonorrhoeae from urogenital and nongenital anatomic sites is superior to culture but varies by NAAT type (553,800803). For urogenital infections, optimal specimen types for gonorrhea screening using NAATs include first-void urine for men and vaginal swab specimens for women (553). Patient-collected samples can be used in place of provider-collected samples in clinical settings when testing by NAAT for urine (men and women), vaginal swabs, rectal swabs, and oropharyngeal swabs after patient instructions have been provided (209,806,839842). Patient-collected specimens are reasonable alternatives to provider-collected swabs for gonorrhea screening by NAAT.

In cases of suspected or documented treatment failure, clinicians should perform both culture and antimicrobial susceptibility testing because NAATs 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 carbon dioxide (CO2) environment (553). Nonnutritive swab transport systems are available that might maintain gonococcal viability for <48 hours in ambient temperatures (843845).

Because of its high specificity (>99%) and sensitivity (>95%), a Gram stain of urethral discharge or secretions that demonstrate polymorphonuclear leukocytes with intracellular gram-negative diplococci can be considered diagnostic for infection with N. gonorrhoeae among symptomatic men. However, because of lower sensitivity, a negative Gram stain should not be considered sufficient for ruling out infection among asymptomatic men. Infection detection by using Gram stain of endocervical, pharyngeal, and rectal specimens also is insensitive and is not recommended. MB or GV stain of urethral secretions is an alternative POC diagnostic test with performance characteristics similar to Gram stain. Gonococcal infection is diagnosed among symptomatic men by documenting the presence of a WBC-containing intracellular purple diplococci in MB or GV smears.

Antimicrobial-Resistant N. gonorrhoeae

Gonorrhea treatment is complicated by the ability of N. gonorrhoeae to develop resistance to antimicrobials (846848). In 1986, the Gonococcal Isolate Surveillance Project (GISP), a national sentinel surveillance system, was established to monitor trends in antimicrobial susceptibilities of urethral N. gonorrhoeae strains in the United States (849). The epidemiology of antimicrobial resistance guides decisions about gonococcal treatment recommendations and has evolved because of shifts in antimicrobial resistance patterns. During 2007, emergence of fluoroquinolone-resistant N. gonorrhoeae in the United States prompted CDC to cease recommending fluoroquinolones for gonorrhea treatment, leaving cephalosporins as the only remaining class of antimicrobials available for gonorrhea treatment in the United States (850). Reflecting concern about emerging gonococcal resistance, CDC’s 2010 STD treatment guidelines recommended dual therapy for gonorrhea with a cephalosporin plus either azithromycin or doxycycline, even if NAAT for C. trachomatis was negative at the time of treatment (851)However, during 2006–2011, the minimum concentrations of cefixime needed to inhibit in vitro growth of the N. gonorrhoeae strains circulating in the United States and other countries increased, demonstrating that cefixime effectiveness might be waning (851). In addition, treatment failures with cefixime or other oral cephalosporins were reported in Asia (852855), Europe (856860), South Africa (861), and Canada (862,863). During that time, case reports of ceftriaxone treatment failures for pharyngeal infections reported in Australia (864,865), Japan (866), and Europe were concerning (856,867). Consequently, CDC no longer recommends cefixime as a first-line regimen for gonorrhea treatment in the United States (868). Since 2013, the proportion of GISP isolates that demonstrate reduced susceptibility (minimal inhibitory concentration [MIC] ≥2.0 µg/mL) to azithromycin has increased almost tenfold, to 5.1% in 2019 (141). Unlike the appearance of ciprofloxacin resistance in the early 2000s, and cefixime reduced-susceptibility isolates during 2010–2011, emergence of azithromycin resistance is not concentrated among certain populations (e.g., MSM in the western United States). Azithromycin has unique pharmacokinetic properties that might predispose to resistance due to its prolonged half-life (869,870). With the exception of a small cluster of gonorrhea strains with azithromycin resistance and reduced susceptibility to cefixime and ceftriaxone among seven patients during 2016, all gonorrhea strains identified by GISP are susceptible to either or both azithromycin and ceftriaxone or cefixime. In addition, since 2013, antimicrobial stewardship has become an urgent public health concern in the United States as described in Antimicrobial Resistant Threats in the United States (871). Emergence of azithromycin resistance is not isolated to N. gonorrhoeae; it has also been demonstrated in M. genitalium and such enteric pathogens as Shigella and Campylobacter (see Mycoplasma genitalium; Proctitis, Proctocolitis, and Enteritis). Finally, concern exists regarding azithromycin treatment efficacy for chlamydia (see Chlamydial Infections).

Dual therapy for gonococcal infection with ceftriaxone and azithromycin recommended in previous guidance might have mitigated emergence of reduced susceptibility to ceftriaxone in N. gonorrhoeae; however, concerns regarding potential harm to the microbiome and the effect on other pathogens diminishes the benefits of maintaining dual therapy. Consequently, only ceftriaxone is recommended for treating gonorrhea in the United States (872). Clinicians remaining vigilant for treatment failures is paramount, and CDC plans to continue to monitor for changing ceftriaxone MICs until additional antimicrobials or a vaccine is available. In cases in which chlamydial infection has not been excluded, patients should also receive antichlamydial therapy. CDC and state health departments participate in CDC-supported gonorrhea surveillance activities (https://www.cdc.gov/std/gisp) and can provide the most current information regarding gonococcal susceptibility.

Criteria for resistance to cefixime and ceftriaxone have not been defined by the Clinical and Laboratory Standards Institute (CLSI). However, isolates with cefixime or ceftriaxone MICs ≥0.5 µg/mL are considered to have decreased susceptibility (873). In the United States, the proportion of isolates in GISP demonstrating decreased susceptibility to ceftriaxone or cefixime has remained low; during 2019, <0.1% of isolates with decreased susceptibility (MIC ≥0.5 µg/mL) to ceftriaxone or cefixime were identified (141). Because increasing MICs might predict resistance emergence, GISP established lower cephalosporin MIC threshold values that are lower than the susceptibility breakpoints set by CLSI to provide greater sensitivity in detecting decreasing gonococcal susceptibility for surveillance purposes. The percentage of isolates with cefixime MICs ≥0.25 µg/mL increased from 0.1% during 2006 to 1.4% during 2011 (851,874) and declined to 0.3% during 2019 (141). The percentage of isolates with ceftriaxone MICs ≥0.125 µg/mL increased from <0.1% in 2006 to 0.4% in 2011 and decreased to 0.1% in 2019 (141). Isolates with high-level cefixime and ceftriaxone MICs (MICs = 1.5–8.0 µg/mL and MICs = 1.5–4.0 µg/mL, respectively) have been identified in Japan (866), France (867,875), Spain (876,877), the United Kingdom, and Australia (878,879). Decreased susceptibility of N. gonorrhoeae to cephalosporins and other antimicrobials is expected to continue; state and local surveillance for antimicrobial resistance is crucial for guiding local therapy recommendations (846,847). Although approximately 3% of all U.S. men who have gonococcal infections are sampled through GISP, surveillance by clinicians also is crucial. Clinicians who diagnose N. gonorrhoeae infection in a person with suspected cephalosporin treatment failure should perform culture and AST of relevant clinical specimens, consult an infectious disease specialist or an STD clinical expert (https://www.stdccn.org/render/Publicexternal icon) for guidance in clinical management, and report the case to CDC through state and local public health authorities within 24 hours. Isolates should be saved and sent to CDC through local and state public health laboratory mechanisms. Health departments should prioritize notification and culture evaluation for sexual partners of persons with N. gonorrhoeae infection thought to be associated with cephalosporin treatment failure or persons whose isolates demonstrate decreased susceptibility to cephalosporin. Agar dilution is the reference standard and preferred method of antimicrobial susceptibility testing with N. gonorrhoeae. Antibiotic gradient strips, such as Etest (bioMérieux), can be used and are considered an acceptable alternative for quantitative antimicrobial susceptibility testing with N. gonorrhoeae when manufacturer instructions are followed. Disc diffusion only provides qualitative susceptibility results.

Uncomplicated Gonococcal Infection of the Cervix, Urethra, or Rectum

Recommended Regimen for Uncomplicated Gonococcal Infection of the Cervix, Urethra, or Rectum Among Adults and Adolescents

Ceftriaxone 500 mg* IM in a single dose for persons weighing <150 kg

If chlamydial infection has not been excluded, treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days.

* For persons weighing ≥150 kg, 1 g ceftriaxone should be administered.

Although clinical data confirm that a single injection of ceftriaxone 250 mg is >99% (95% confidence interval [CI]: 97.6%–99.7%) effective in curing anogenital gonorrhea of circulating isolates (MIC = 0.03 µg/mL), a higher dose is likely necessary for isolates with elevated MICs (880,881). Effective treatment of uncomplicated urogenital gonorrhea with ceftriaxone requires concentrations higher than the strain MIC for approximately 24 hours; although individual variability exists in the pharmacokinetics of ceftriaxone, a 500-mg dose of ceftriaxone is expected to achieve in approximately 50 hours MIC >0.03 µg/mL (880,881). The pharmacokinetics of ceftriaxone might be different in the pharynx with longer times higher than the strain MIC likely needed to prevent selection of mutant strains in the pharynx (882).

Single-dose injectable cephalosporin regimens, other than ceftriaxone, that are safe and have been effective against uncomplicated urogenital and anorectal gonococcal infections in the past include ceftizoxime (500 mg IM), cefoxitin (2 g IM with probenecid 1 g orally), and cefotaxime (500 mg IM). None of these injectable cephalosporins offer any advantage over ceftriaxone 250 mg for urogenital infection, and efficacy for pharyngeal infection is less certain (883,884). Because the ceftriaxone dose has been increased and the pharmacokinetics of other cephalosporins have not been evaluated, these dosing regimens might be at a disadvantage over ceftriaxone 500 mg.

Alternative Regimens if Ceftriaxone Is Not Available

Gentamicin 240 mg IM in a single dose

PLUS

Azithromycin 2 g orally in a single dose

OR

Cefixime 800 mg* orally in a single dose

* If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days.

In one clinical trial, dual treatment with single doses of IM gentamicin 240 mg plus oral azithromycin 2 g cured 100% of cases (lower one-sided 95% CI bound: 98.5%) and can be considered an alternative to ceftriaxone for persons with cephalosporin allergy (885). This trial was not powered enough to provide reliable estimates of the efficacy of these regimens for treatment of rectal or pharyngeal infection; however, this regimen cured the few extragenital infections among study participants. Notably, gastrointestinal adverse events, primarily vomiting <1 hour after dosing, occurred among 3%–4% of persons treated with gentamicin plus azithromycin, necessitating retreatment with ceftriaxone and azithromycin. A similar trial that studied gentamicin 240 mg plus azithromycin 1 g determined lower cure rates at extragenital sites; 80% (95% CI: 72%–88%) of pharyngeal and 90% (95% CI: 84%–95%) of rectal infections were cured with this regimen (886). Gemifloxacin plus azithromycin has been studied and is no longer recommended as an alternative regimen because of limited availability, cost, and antimicrobial stewardship concerns (885).

An 800-mg oral dose of cefixime should be considered only as an alternative cephalosporin regimen because it does not provide as high, nor as sustained, bactericidal blood levels as a 500-mg IM dose of ceftriaxone. Furthermore, it demonstrates limited efficacy for treatment of pharyngeal gonorrhea (92.3% cure; 95% CI: 74.9%–99.1%); in older clinical studies, cefixime cured 97.5% of uncomplicated urogenital and anorectal gonococcal infections (95% CI: 95.4%–99.8%) (883,884). The increase in the prevalence of isolates obtained through GISP with elevated cefixime MICs might indicate early stages of development of clinically significant gonococcal resistance to cephalosporins. Changes in cefixime MICs can result in decreasing effectiveness of cefixime for treating urogenital gonorrhea. Furthermore, as cefixime becomes less effective, continued used of cefixime might hasten the development of resistance to ceftriaxone, a safe, well-tolerated, injectable cephalosporin and the last antimicrobial known to be highly effective in a single dose for treatment of gonorrhea at all anatomic infection sites. Other oral cephalosporins (e.g., cefpodoxime and cefuroxime) are not recommended because of inferior efficacy and less favorable pharmacodynamics (883).

Monotherapy with azithromycin 2 g orally as a single dose has been demonstrated to be 99.2% effective against uncomplicated urogenital gonorrhea (95% CI: 97.3%–99.9%) (883). However, monotherapy is not recommended because of concerns about the ease with which N. gonorrhoeae can develop resistance to macrolides, the high proportion of isolates with azithromycin decreased susceptibility, and documented azithromycin treatment failures (859). Strains of N. gonorrhoeae circulating in the United States are not adequately susceptible to penicillin, tetracycline, and older macrolides (e.g., erythromycin), and thus use of these antimicrobials cannot be recommended.

Spectinomycin is effective (98.2% in curing uncomplicated urogenital and anorectal gonococcal infections) but has poor efficacy for pharyngeal infections (883,887). It is unavailable in the United States, and the gentamicin alternative regimen has replaced the need for spectinomycin, if a cephalosporin allergy exists, in the United States.

Uncomplicated Gonococcal Infection of the Pharynx

The majority of gonococcal infections of the pharynx are asymptomatic and can be relatively common among certain populations (800,801,888890). Although these infections rarely cause complications, they have been reported to be a major source of community transmission and might be a driver of antimicrobial resistance (891,892). Gonococcal infections of the pharynx are more difficult to eradicate than infections at urogenital and anorectal sites (862). Few antimicrobial regimens reliably cure >90% of gonococcal pharyngeal infections (883,884). Providers should ask their patients with urogenital or rectal gonorrhea about oral sexual exposure; if reported, pharyngeal testing should be performed.

Recommended Regimen for Uncomplicated Gonococcal Infection of the Pharynx Among Adolescents and Adults

Ceftriaxone 500 mg* IM in a single dose for persons weighing <150 kg

* For persons weighing ≥150 kg, 1 g ceftriaxone should be administered.

If chlamydial infection is identified when pharyngeal gonorrhea testing is performed, treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days. No reliable alternative treatments are available for pharyngeal gonorrhea. For persons with an anaphylactic or other severe reaction (e.g., Stevens Johnson syndrome) to ceftriaxone, consult an infectious disease specialist for an alternative treatment recommendation.

Other Management Considerations

To maximize adherence with recommended therapies and reduce complications and transmission, medication for gonococcal infection should be provided on-site and directly observed. If medications are unavailable when treatment is indicated, linkage to an STI treatment facility should be provided for same-day treatment. To minimize disease transmission, persons treated for gonorrhea should be instructed to abstain from sexual activity for 7 days after treatment and until all sex partners are treated (7 days after receiving treatment and resolution of symptoms, if present). All persons who receive a diagnosis of gonorrhea should be tested for other STIs, including chlamydia, syphilis, and HIV. Those persons whose HIV test results are negative should be offered HIV PrEP.

Follow-Up

A test of cure (i.e., repeat testing after completion of therapy) is unnecessary for persons who receive a diagnosis of uncomplicated urogenital or rectal gonorrhea who are treated with any of the recommended or alternative regimens. Any person with pharyngeal gonorrhea should return 7–14 days after initial treatment for a test of cure by using either culture or NAAT; however, testing at 7 days might result in an increased likelihood of false-positive tests. If the NAAT is positive, effort should be made to perform a confirmatory culture before retreatment, especially if a culture was not already collected. 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 antimicrobial susceptibility. Persistent urethritis, cervicitis, or proctitis also might be caused by other organisms (see Urethritis; Cervicitis; Proctitis).

A high prevalence of N. gonorrhoeae infection has been observed among men and women previously treated for gonorrhea (137,753,754,893). The majority 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; scheduling the follow-up visit at the time of treatment is encouraged. If retesting at 3 months is not possible, clinicians should retest whenever persons next seek medical care <12 months after initial treatment.

Management of Sex Partners

Recent sex partners (i.e., persons having sexual contact with the infected patient <60 days preceding onset of symptoms or gonorrhea diagnosis) should be referred for evaluation, testing, and presumptive treatment. If the patient’s last potential sexual exposure was >60 days before onset of symptoms or diagnosis, the most recent sex partner should be treated.

If health department partner-management strategies (e.g., disease intervention specialists) are impractical or unavailable for persons with gonorrhea and partners’ access to prompt clinical evaluation and treatment is limited, EPT can be delivered to the partner by the patient or a collaborating pharmacy as permitted by law (see Partner Services). Treatment of the sexual partner with cefixime 800 mg as a single dose is recommended, provided that concurrent chlamydial infection has been excluded. If a chlamydia test result has not been documented, the partner may be treated with a single dose of oral cefixime 800 mg plus oral doxycycline 100 mg 2 times/day for 7 days. If adherence with multiday dosing is a considerable concern, azithromycin 1 g can be considered but has lower treatment efficacy among persons with rectal chlamydia (see Chlamydial Infections). Provision of medication by EPT should be accompanied by written materials (125,127) for educating partners about gonorrhea, their exposure to gonorrhea, and the importance of therapy. These materials should also educate partners about seeking clinical evaluation for adverse reactions or complications and general follow-up when able. Educational materials for female partners should include information about the importance of seeking medical evaluation for PID, especially if symptomatic; undertreatment of PID among female partners and missed opportunities for diagnosing other STIs among women are of concern. MSM with gonorrhea have a high risk for coexisting infections (especially undiagnosed HIV) among their partners, and they might have partners without HIV who could benefit from PrEP. Data are also limited regarding the effectiveness of EPT in reducing persistent or recurrent gonorrhea among MSM (133,135); thus, shared clinical decision-making regarding EPT for MSM is recommended (see Partner Services). To avoid reinfection, sex partners should be instructed to abstain from condomless sexual intercourse for 7 days after they and their sex partners have completed treatment and after resolution of symptoms, if present.

Suspected Cephalosporin Treatment Failure

Cephalosporin treatment failure is the persistence of N. gonorrhoeae infection despite recommended cephalosporin treatment; such failure is indicative of infection with cephalosporin-resistant gonorrhea among persons whose partners were treated and whose risk for reinfection is low. Suspected treatment failure has been reported among persons receiving oral and injectable cephalosporins (852855,857,859,861,863,864,867,875,894). Treatment failure should be considered for persons whose symptoms do not resolve within 3–5 days after recommended treatment and report no sexual contact during the posttreatment follow-up period and 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 posttreatment follow-up period (874). Treatment failure should also be considered for persons who have a positive culture on test of cure, if obtained, if evidence exists of decreased susceptibility to cephalosporins on antimicrobial susceptibility testing, regardless of whether sexual contact is reported during the posttreatment follow-up period.

The majority of suspected treatment failures in the United States are likely to be reinfections rather than actual treatment failures (137,753,754,894). However, in cases in which 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 by using Etest or agar dilution. 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 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 https://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, the National Network of STD Clinical Prevention Training Center clinical consultation line (https://www.stdccn.org/render/Publicexternal icon), the local or state health department STI program, or CDC (telephone: 800-232-4636) for advice about obtaining cultures, antimicrobial susceptibility testing, and treatment. Suspected treatment failure should be reported to CDC through the local or state health department <24 hours after diagnosis.

Patients with suspected treatment failures should first be retreated routinely with the initial regimen used (ceftriaxone 500 mg IM), with the addition of doxycycline if chlamydia infection exists, 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 before retreatment. Dual treatment with single doses of IM gentamicin 240 mg plus oral azithromycin 2 g can be considered, particularly when isolates are identified as having elevated cephalosporin MICs (885,886,895). Persons with suspected treatment failure after treatment with the alternative regimen (cefixime or gentamicin) should be treated with ceftriaxone 500 mg as a single IM dose or as a single dose with or without an antichlamydial agent on the basis of chlamydia infection status. 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 patients’ sex partners from the preceding 60 days are evaluated promptly with culture and presumptively treated by using the same regimen used for the patients.

Special Considerations

Drug Allergy, Intolerance, and Adverse Reactions

The risk for penicillin cross-reactivity is highest with first-generation cephalosporins but is rare (<1%) with third-generation cephalosporins (e.g., ceftriaxone and cefixime) (631,680,896). Clinicians should first thoroughly assess a patient’s allergy history, including type of reaction, associated medications, and previous prescription records. If IgE-mediated penicillin allergy is strongly suspected, dual treatment with single doses of IM gentamicin 240 mg plus oral azithromycin 2 g can be administered (885,886). If a patient is asymptomatic and the treating facility is able to perform gyrase A (gyrA) testing to identify ciprofloxacin susceptibility (wild type), oral ciprofloxacin 500 mg in a single dose can be administered. Providers treating persons with IgE-mediated cephalosporin or penicillin allergy should refer to the section of these guidelines regarding evaluation (see Management of Persons Who Have a History of Penicillin Allergy).

Pregnancy

Pregnant women infected with N. gonorrhoeae should be treated with ceftriaxone 500 mg in a single IM dose plus treatment for chlamydia if infection has not been excluded. When cephalosporin allergy or other considerations preclude treatment with this regimen, consultation with an infectious disease specialist or an STD clinical expert is recommended (https://www.stdccn.org/render/Publicexternal icon). Gentamicin use is cautioned during pregnancy because of risk for neonatal birth defects, nephrotoxicity, or ototoxicity (897).

HIV Infection

Persons who have gonorrhea and HIV infection should receive the same treatment regimen as those who do not have HIV.

Gonococcal Conjunctivitis

In the only published study of the treatment regarding gonococcal conjunctivitis among adults, all 12 study participants responded to a single 1-g IM injection of ceftriaxone (898). Because gonococcal conjunctivitis is uncommon and data regarding treatment of gonococcal conjunctivitis among adults are limited, consultation with an infectious disease specialist should be considered.

Recommended Regimen for Gonococcal Conjunctivitis Among Adolescents and Adults

Ceftriaxone 1 gm IM in a single dose

Providers should 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 (see Gonococcal Infections, Management of Sex Partners).

Disseminated Gonococcal Infection

Infrequently, N. gonorrhoeae can cause disseminated infection. Disseminated gonococcal infection (DGI) frequently results in petechial or pustular acral skin lesions, asymmetric polyarthralgia, tenosynovitis, or oligoarticular septic arthritis (899901). Rarely, DGI is complicated by perihepatitis associated with gonococcal PID, endocarditis, or meningitis. Certain strains of N. gonorrhoeae that cause DGI can cause minimal genital inflammation, and urogenital or anorectal infections are often asymptomatic among DGI patients. If DGI is suspected, NAAT or culture specimens from all exposed urogenital and extragenital sites should be collected and processed, in addition to NAAT and culture specimens from disseminated sites of infection (e.g., skin, synovial fluid, blood, or CNS). All N. gonorrhoeae isolates should be tested for antimicrobial susceptibility. Risk factors for dissemination have included female sex, menstruation, pregnancy, and terminal complement deficiency (899); however, reports are increasing among men (900,901). Persons receiving eculizumab, a monoclonal antibody that inhibits terminal complement activation, also might be at higher risk for DGI (902).

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 for Gonococcal-Related Arthritis and Arthritis-Dermatitis Syndrome

Ceftriaxone 1 g IM or by IV every 24 hours

If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days.

Alternative Regimens

Cefotaxime 1 g by IV every 8 hours

OR

Ceftizoxime 1 g every 8 hours

If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days.

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 for Gonococcal Meningitis and Endocarditis

Ceftriaxone 1–2 g IV every 24 hours

If chlamydial infection has not been excluded, providers should treat for chlamydia with doxycycline 100 mg orally 2 times/day for 7 days.

No recent studies have been published regarding treatment of DGI involving the CNS or cardiovascular system. The duration of treatment for DGI in these situations 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. Length of treatment should be determined based on 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 >4 weeks. Treatment of gonococcal perihepatitis should be managed in accordance with the recommendations for PID in these guidelines.

Management of Sex Partners

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