Alternatives to Spectinomycin for the Treatment of Neisseria Gonorrhoeae

The recent announcement of the discontinuation of spectinomycin production in the United States has prompted alternative recommendations for the treatment of Neisseria gonorrhoeae in those persons with contraindications to cephalosporins and fluoroquinolones. There are relatively few indications for which spectinomycin was the preferred treatment option, as it is expensive and must be injected. Such scenarios include pregnant women with documented cephalosporin allergy (as fluoroquinolones are contraindicated in pregnancy), and persons with documented cephalosporin allergies acquired in geographic areas where fluoroquinolone-resistant gonorrhea is endemic. The following interim recommendations are given below.

PREGNANT WOMEN WITH DOCUMENTED CEPHALOSPORIN ALLERGY

Immediate (30-60 minutes after administration) and accelerated (1-12 hours after administration) immunoglobin E medicated anaphylactic or urticarial reactions to cephalosporins are rare relative to those associated with penicillin [1]. Cephalosporin reactions occur in 1%-7% of persons with a history of penicillin allergy [2]. There is no available test that can predict who is at risk for these reactions, as skin testing for cephalosporins is unreliable. Therapy with non-beta lactam antibiotics should be used if severe beta lactam reactions, especially those mediated by IgE, have occurred.

The 1998 CDC STD Treatment Guidelines [3] recommend that pregnant women should not be treated with quinolone antibiotics. The selection of alternative antibiotic therapy in persons with a history of a reaction to a cephalosporin must be guided by the severity of the reaction and the availability of suitable alternative regimens.

There have been no studies documenting the efficacy of alternative agents in pregnant women. As such, management of gonococcal infection in the pregnant women should include rapid cephalosporin desensitization in consultation with an expert. Although azithromycin 2 gm orally in a single dose is effective against uncomplicated gonococcal infection, there are no data documenting safety and efficacy for this regimen in pregnant women, which causes significant gastrointestinal distress in non-pregnant adults at this dose. As persons infected with N. gonorrhoeae often are coinfected with C. trachomatis treatment of presumptive or diagnosed C. trachomatis infection during pregnancy should include either erythromycin (500 mg orally four times daily for seven days) or amoxicillin (500 mg orally three times daily for seven days).

FLUOROQUINOLONE RESISTANCE (QRNG) AND DOCUMENTED CEPHALOSPORIN ALLERGY

Although infections with QRNG are endemic in many Asian countries and the Pacific, reports have documented only sporadic isolation of these strains in the United States, except in Hawaii. Less than 0.4% of 5180 isolates collected by CDC's Gonococcal Isolate Surveillance Project (GISP) during 1999 had minimum inhibitory concentrations (MICs) ≥ 1.0 µg/mL to ciprofloxacin. The resistant isolates made up 0.2% of the GISP sample of the 25 GISP cities in the continental United States and Alaska but comprised 14.3% of the Honolulu GISP sample. Because of these and other data, quinolones are no longer recommended for the treatment of gonorrhea in the state of Hawaii and should not be used to treat infections that may have been acquired in Asia or the Pacific (including Hawaii).

There are no standard alternative regimens for non-pregnant persons who acquire gonorrhea infection in areas with endemic QRNG and who have documented cephalosporin allergy. Administration of azithromycin 2 gm orally is approved for gonorrhea therapy by the Food and Drug Administration, but the current CDC guidelines do not recommend its routine use in nonpregnant adults because of gastrointestinal intolerance at this dose [3] . Efficacy of this regimen in clinical trials has demonstrated acceptable cure rates of 97.2%-99.9% for urogenital and rectal infections. However due to the possibility of severe gastrointestinal distress, persons should be observed for at least 30 minutes after ingestion to monitor tolerance of the medication. Administration of azithromycin at a one gram dose is insufficiently effective and is not recommended.

1. Lin R. A perspective on penicillin allergy. Arch Intern Med 1992;152:930-937.

2. Saxon A, Beall GN, Rohr AS, et al. Immediate hypersensitivity reactions to beta-lactam antibiotics. Ann Intern Med 1987;107:204-215.

3. CDC. 1998 Guidelines for the treatment of sexually transmitted diseases. MMWR 1998;47(no. RR-1):1-116.