The American College of

Obstetricians and Gynecologists

WOMEN’S HEALTH CARE PHYSICIANS

COMMITTEE OPINION
Number 645 • November 2015

Committee on Gynecologic Practice

This document reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information should
not be construed as dictating an exclusive course of treatment or procedure to be followed.

Dual Therapy for Gonococcal Infections

ABSTRACT: Gonorrhea is the second most commonly reported bacterial sexually transmitted disease in the
United States, with an estimated 820,000 new Neisseria gonorrhoeae infections occurring each year. Antimicrobial
resistance limits treatment success, heightens the risk of complications, and may facilitate the transmission of
sexually transmitted infections. Neisseria gonorrhoeae has developed resistance to the sulfonamides, the tetracy-
clines, and penicillin. Dual therapy with ceftriaxone and azithromycin remains the only recommended first-line regi-
men for the treatment of gonorrhea in the United States. Dual therapy with ceftriaxone and azithromycin should
be administered together on the same day, preferably simultaneously, and under direct observation. Pregnant
women who are infected with N gonorrhoeae should be treated with the recommended dual therapy. A test-of-
cure is not needed for individuals diagnosed with uncomplicated urogenital or rectal gonorrhea who are treated
with the recommended or alternative regimens. Repeat N gonorrhoeae infection is prevalent among patients who
have been diagnosed with and treated for gonorrhea in the preceding several months. Most of these infections
result from reinfection; therefore, clinicians should advise patients with gonorrhea to be retested 3 months after
treatment. Pregnant women with antenatal gonococcal infection should be retested in the third trimester unless
recently treated.

Recommendations the treatment of gonococcal infections is likely

Based on the following information, the American Col- to evolve in the coming years, and obstetrician–
lege of Obstetricians and Gynecologists makes these gynecologists should remain aware of new develop-
recommendations: ments in this area. The CDC web site (www.cdc.
gov/std/gisp/) and state health departments can pro-
• Dual therapy with ceftriaxone and azithromycin vide the most current information on gonococcal
should be administered. It should be administered susceptibility.
together on the same day, preferably simultaneously,
and under direct observation. Gonorrhea is the second most commonly reported bac-
terial sexually transmitted disease (STD) in the United
• Test-of-cure is not recommended for women diag-
States, with an estimated 820,000 new Neisseria gonor-
nosed with uncomplicated urogenital or rectal gon-
rhoeae infections occurring each year (1). Antimicrobial
orrhea treated with the recommended or alternative
resistance limits treatment success, heightens the risk of
regimens.
complications, and may facilitate the transmission of sex-
• Pregnant women treated with dual therapy for gon- ually transmitted infections (STIs). Neisseria gonorrhoeae
orrhea do not require a test-of-cure. has developed resistance to sulfonamides, tetracyclines,
• Women with pharyngeal gonorrhea treated with an and penicillin. In 2007, emergence of fluoroquinolone-
alternative regimen should return 14 days after treat- resistant N gonorrhoeae prompted the CDC to no longer
ment for a test-of-cure using either culture or nucleic recommend fluoroquinolones for treatment of gonor-
acid amplification test (NAAT). rhea, leaving cephalosporins as the only remaining class
• The Centers for Disease Control and Prevention’s of recommended antimicrobials (2).
(CDC) guidance (www.cdc.gov/mmwr/preview/ In an attempt to prevent development of resis-
mmwrhtml/rr6403a1.htm?s_cid=rr6403a1_e) on tance to cephalosporins, the CDC’s 2010 STD treatment
guidelines recommended combination therapy for gon- is safe and effective for the treatment of uncomplicated
orrhea with a cephalosporin plus either azithromycin or gonorrhea at all anatomic sites, curing more than 98%
doxycycline, even if NAAT for Chlamydia trachomatis of all infections (6, 7). The use of azithromycin as the
was negative at the time of treatment (3). This emerging second antimicrobial is preferred to doxycycline because
cephalosporin resistance was manifested from 2006 to of the convenience and adherence advantages of single-
2011, when the minimum inhibitory concentrations of dose therapy and the substantially higher prevalence of
cefixime needed to inhibit the growth in vitro of N gonor- gonococcal resistance to tetracycline than to azithromycin
rhoeae strains in the United States increased, suggesting (1, 8). The use of ceftriaxone or cefixime is contraindi-
that the effectiveness of cefixime might be waning (4, 5). cated in those patients with a history of an IgE mediated
As a result, cefixime is no longer a first-line regimen. Dual b-lactam allergy, such as anaphylaxis, Stevens–Johnson
therapy with ceftriaxone and azithromycin remains the syndrome, or toxic epidermal necrolysis (see Box 1 for
only recommended first-line regimen for the treatment alternate treatment regimens) (9, 10).
of gonorrhea in the United States (1, 5). Recent clinical trials showed that dual treatment
with a single 320-mg dose of oral gemifloxacin plus a
Treatment Regimens 2-g dose of oral azithromycin, or dual treatment with
Dual therapy with ceftriaxone and azithromycin should a single 240-mg dose of IM gentamicin plus a 2-g dose
be administered together on the same day, preferably of oral azithromycin, were effective for uncomplicated
simultaneously, and under direct observation (see Box 1). urogenital gonorrhea (11). Either of these regimens may
Ceftriaxone in a single-intramuscular (IM) injection of be considered as alternative treatment options when cef-
250 mg provides sustained, high bactericidal levels in triaxone is contraindicated. Monotherapy with a 2-g dose
the blood; clinical experience indicates that ceftriaxone of oral azithromycin as a single dose in women who are
not pregnant is no longer recommended in the United
States (12–16).
Box 1. Recommended Antibiotic Pregnancy
Regimens for Treatment of Pregnant women who are infected with N gonorrhoeae
Uncomplicated Gonococcal Infections of should be treated with the recommended dual therapy. A
the Cervix, Urethra, and Rectum ^ test-of-cure is not needed for individuals diagnosed with
Preferred Regimen (First Line)
uncomplicated urogenital or rectal gonorrhea who are
treated with the recommended or alternative regimen.
Ceftriaxone, 250 mg, single-intramuscular dose Patients with severe penicillin or cephalosporin allergy
plus can be administered dual therapy with a 240-mg dose
Azithromycin, 1 g, single-oral dose* of IM gentamicin and 2-g oral azithromycin. The use of
Alternative Regimens (Second Line) gentamicin to treat chorioamnionitis demonstrates its
If ceftriaxone is not available
safety in pregnancy (17, 18). Based on expert opinion,
another alternative is a 2-g single dose of oral azithro-
Cefixime, 400 mg, single-oral dose mycin in patients who are allergic to gentamicin and
plus cephalosporins, but this category of patients need a test-
Azithromycin, 1 g, single-oral dose* of-cure 1 week after treatment. Such patients also may
If the patient has a severe penicillin allergy be referred to an infectious disease specialist. Dual therapy
Gemifloxacin, 320 mg, single-oral dose with ceftriaxone and azithromycin is recommended if the
patient has a history of rash without anaphylaxis manifes-
plus
tations. Neither doxycycline nor quinolones are recom-
Azithromycin, 2 g, single-oral dose mended during pregnancy.
or
Gentamicin, 240 mg, single-intramuscular dose Human Immunodeficiency Virus
plus
Infection
Azithromycin, 2 g, single-oral dose* Patients infected with human immunodeficiency virus
(HIV) with gonococcal infection should receive the same
*If azithromycin is not available or if the patient is allergic to recommended dual therapy as those who do not have HIV
azithromycin, doxycycline (100 mg orally twice a day for 7 days)
may be substituted as the second antimicrobial. (1). See general treatment recommendations described
Note the following: under “Treatment Regimens.”
• Dose of azithromycin is increased to 2 g when used with the
alternative antibiotics, gemifloxacin or gentamicin. Management of Sex Partners
• Dual therapy with gentamicin and azithromycin or azithromy- Recent sex partners within 60 days of diagnosis should
cin alone should be used during pregnancy. be encouraged to seek evaluation and presumptive treat-
ment for N gonorrhoeae and C trachomatis infections.

2 Committee Opinion No. 645

If the last potential exposure was greater than 60 days, failure also should be considered in individuals who have
the most recent sex partner should be treated. Patients a positive culture on test-of-cure (if obtained) and there
and sex partners should abstain from sexual activity for is evidence of decreased susceptibility to cephalospo-
7 days after treatment and until sex partners are adequately rins on antimicrobial susceptibility testing, regardless of
treated. If an obstetrician–gynecologist or other health whether sexual contact is reported during the posttreat-
care provider cannot ensure that an infected patient’s ment follow-up period.
partner will be promptly linked to care, and where In cases where reinfection is unlikely and treatment
legally accepted, expedited partner therapy with cefixime failure is suspected, before retreatment of the individual,
(400 mg) and azithromycin (1 g) should be delivered to relevant clinical specimens should be obtained for culture
the partner by the patient, a disease investigation special- (preferably with simultaneous NAAT) and antimicrobial
ist, or through a collaborating pharmacy. The CDC main- susceptibility testing should be performed if N gonor-
tains a web site with information about the legal status rhoeae is isolated. All isolates should be sent to the CDC
of expedited partner therapy in all 50 states and other for antimicrobial susceptibility testing; local laboratories
jurisdictions (19); additional information is available should store isolates for possible further testing if needed.
from the Guttmacher Institute (20). More information Instructions for shipping isolates to CDC can be found
on expedited partner therapy is available in the American at www.cdc.gov/std/gonorrhea/arg/specimen_shipping_
College of Obstetricians and Gynecologists’ Committee instructions1-29-08.pdf (24).
Opinion Number 632, Expedited Partner Therapy in the For individuals with suspected cephalosporin treat-
Management of Gonorrhea and Chlamydial Infection (21). ment failure, the treating clinician should consult an
Expedited partner therapy should be accompanied by infectious disease specialist, an STD/HIV Prevention
written materials educating partners about their exposure Training Center clinical expert (www.nnptc.org) (25),
to gonorrhea, the importance of therapy, and when to the local or state health department STD program, or
seek clinical evaluation for reactions or complications. the CDC for advice. Dual treatment with a single 320-mg
dose of oral gemifloxacin plus a 2-g dose of oral azithro-
Retesting mycin or dual treatment with a single 240-mg dose of
Appropriately treated patients do not need a test-of-cure. gentamicin IM plus a 2-g dose of oral azithromycin may
Retesting to detect repeat infection is distinct from test- be considered, particularly when isolates are found to
of-cure to detect therapeutic failure. For patients who get have elevated cephalosporin minimum inhibitory con-
retested and receive positive test results, most are more centrations (26). Individuals with suspected treatment
likely to be from reinfection than from treatment failure. failure after treatment with the alternative regimen (cefix-
Such patients should be retreated with the recommended ime and azithromycin) should be treated with a single
dual regimen (250 mg of ceftriaxone IM plus 1 g of azith- 250-mg IM dose of ceftriaxone and a single 2-g oral dose
romycin orally). Patients who have symptoms that per- of azithromycin. A test-of-cure at relevant clinical sites
sist after treatment should be evaluated by culture for should be obtained 7–14 days after retreatment; culture
N gonorrhoeae (preferably with simultaneous NAAT), and is the recommended test, preferably with simultaneous
any gonococci isolated should be tested for antimicrobial NAAT and antimicrobial susceptibility testing of N gon-
susceptibility. Persistent urethritis, cervicitis, or proctitis orrhoeae if isolated. Obstetrician–gynecologists or other
also might be caused by C trachomatis or other organisms. health care providers should encourage the patient’s
sex partners from the preceding 60 days to seek prompt
Suspected Cephalosporin Treatment evaluation with culture and presumptive treatment using
Failure the same regimen used for the patient.
Cephalosporin treatment failure is defined as the persis-
tence of N gonorrhoeae infection despite appropriate Follow-Up
cephalosporin treatment and is indicative of infection Repeat N gonorrhoeae infection is prevalent among
with cephalosporin-resistant gonorrhea in individuals patients who have been diagnosed with and treated for
whose partners were adequately treated and whose risk of gonorrhea in the preceding several months (27–29).
reinfection is low. Suspected treatment failure has been Most of these infections result from reinfection and
reported among individuals receiving oral and inject- clinicians should therefore advise patients with gonor-
able cephalosporins (22, 23). Treatment failure should rhea to be retested 3 months after treatment. If patients
be considered in individuals whose symptoms do not do not seek medical care for retesting in 3 months,
resolve within 3–5 days after appropriate treatment and obstetrician–gynecologists or other health care provid-
who report no sexual contact during the posttreatment ers are encouraged to test these patients whenever they
follow-up period, and in individuals with a positive test- next seek medical care within the following 12 months,
of-cure (eg, a positive culture after more than 72 hours or regardless of whether the patients believe that their sex
a positive NAAT result 7 or more days after receiving rec- partners were treated. Pregnant women with antenatal
ommended treatment) and who report no sexual contact gonococcal infection should be retested in the third
during the posttreatment follow-up period. Treatment trimester unless recently treated.

Committee Opinion No. 645 3

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Committee Opinion No. 645 5