Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Cefixime was as effective as ceftriaxone in gonorrhea

ACP J Club. 1992 Mar-April;116:52. doi:10.7326/ACPJC-1992-116-2-052


Source Citation

Handsfield HH, McCormack WM, Hook EW 3d, et al. A comparison of single-dose cefixime with ceftriaxone as treatment for uncomplicated gonorrhea. N Engl J Med. 1991 Nov 7;325:1337-41.


Abstract

Objective

To evaluate the efficacy of single-dose oral cefixime compared with intramuscular ceftriaxone in patients with Neisseria gonorrhoeae.

Design

Randomized, multicenter trial.

Setting

Sexually transmitted disease clinics in 4 U.S. cities.

Patients

Participants (209 men and 124 women) had gram-negative diplococci within polymorphonuclear leukocytes on urethral or endocervical smear or, if women, had a history of sexual exposure to a man with gonorrhea. Pregnant or nursing patients and those with gastrointestinal, hepatic, or renal disease; complicated gonorrhea; or hypersensitivity to β-lactam drugs were excluded. Efficacy was evaluated 3 to 10 days after treatment in 275 of 333 patients enrolled (83%); tolerance was assessed in 302 patients (91%).

Intervention

Patients were randomly assigned to treatment with oral cefixime, 400 mg or 800 mg, or intramuscular ceftriaxone, 250 mg.

Main outcome measures

Efficacy was based on pre- and post-treatment culture results obtained from urethral, pharyngeal, or rectal specimens from men or from endocervical, rectal, or pharyngeal specimens from women. Gonococcal isolates were confirmed by carbohydrate-utilization tests or immunochemical methods. β-lactamase production was determined by the chromogenic cephalosporin method. Plasmid-mediated tetracycline resistance was defined by a tetracycline minimal inhibitory concentration (MIC) of ≥ 16 mg/L. Chromosomally mediated resistance was present if the MIC of tetracycline was 2.0 to 8.0 mg/L or if the isolate did not produce β-lactamase and the MIC of penicillin G was ≥ 2.0 mg/L.

Main results

The cure rates for treatment with cefixime, 400 mg; cefixime, 800 mg; and ceftriaxone, 250 mg, were 96% (95% CI 94% to 98%), 98% (CI 95% to 100%), and 98% (CI 95% to 100%), respectively. Gonorrhea was cured in 164 of 167 patients (98%) infected with susceptible strains, in 23 of 24 patients (96%) with chromosomally mediated resistance, in 70 of 73 patients (96%) with β-lactamase producing strains, and in 28 of 29 patients (97%) with plasmid-mediated tetracycline-resistant gonococci. There was no overall difference in adverse effects (n = 44; 86% mild, 14% moderate), although more patients receiving cefixime, 800 mg, had gastrointestinal side effects (16 patients [18%] vs 9 patients given cefixime, 400 mg [8%] and 4 patients given ceftriaxone [4%], P = 0.004).

Conclusion

Single doses of oral cefixime, 400 mg or 800 mg, and of intramuscular ceftriaxone, 250 mg, had similar efficacy for the treatment of uncomplicated gonorrhea.

Source of funding: Lederle Laboratories.

Address for article reprint: Dr. H.H. Handsfield, Harborview Medical Center ZA-89, 325 Ninth Avenue, Seattle, WA 98104, USA.


Commentary

In the United States during the last 2 decades, gonorrhea was the only sexually transmitted infection that decreased in incidence. Although this is good news, the decline in overall gonorrhea rates represented the aggregate effect of 2 competing trends: the rapid decline of N. gonorrhoeae strains sensitive to penicillin and the slower rise in gonococcal strains resistant to this antibiotic (1). As a result, by 1992, gonococcal organisms resistant to penicillin formed more than 10% of strains in North America and a much larger percentage of strains worldwide.

The study by Handsfield and coworkers reflects our continued attempts to keep the treatment regimens for gonorrhea ahead of the microorganism's ability to resist them. Because of widespread antimicrobial resistance to penicillin, intramuscular ceftriaxone (250 mg) had become the drug of choice for gonorrhea (2). However, a single-dose oral antibiotic regimen would be preferable, given its ease of administration, higher compliance, and greater patient comfort (3).

In this randomized trial, the study group in the 4 sexually transmitted disease clinics had at least 1 type of resistance demonstrated in 39% of cases, which approaches the prevalence of resistance seen in some centers in both developed and underdeveloped countries. Despite this high level of resistance, all 3 drug regimens tested were associated with cure rates of 95% or more and with minimal side effects. In conclusion, this study demonstrated that oral cefixime is a useful addition as a therapeutic agent against uncomplicated gonorrhea infections.

Willard Cates, Jr., MD, MPH
Centers for Disease ControlAtlanta, Georgia, USA


References

1. Schwarcz SK, Zenilman JM, Schnell D, et al. JAMA. 1990;264:1413-7.

2. Centers for Disease Control. MMWR. 1989;38(S-8):21-3.

3. Moran JS, Zenilman JM. Rev Infect Dis. 1990;12(Suppl 6):S633-44.


Author's Response

The Medical Letter (1991 Dec 27;33:119-24) recommended cefixime, 400 mg, as an effective oral single-dose alternative to ceftriaxone for gonorrhea.

H. Hunter Handsfield, MD