Treatment options narrow for gonorrhea

With fluoroquinolone-resistant gonorrhea becoming more common in the United States, clinicians have looked to two treatment alternatives, cefixime and ceftriaxone, to combat the sexually transmitted disease (STD). With news that the manufacturer of cefixime has discontinued U.S. production of the drug, clinicians need to review their strategy to battle the infection.

The fluoroquinolones ciprofloxacin, ofloxacin, and levofloxacin are not recommended for treatment of gonorrhea infections acquired in Hawaii, California, Asia, the Pacific, and in other areas with increased prevalence of fluoroquinolone resistance, according to the Atlanta-based Centers for Disease Control and Prevention (CDC).1 Providers in other areas of the United States can continue to use the drugs for gonococcal infections in areas where the prevalence of fluoroquinolone resistance is less than 1%; however, clinicians should be alert to the possible appearance of fluoroquinolone-resistant strains of the infection.

"Our current recommendations for the treatment of uncomplicated urogenital Neisseria gonorrhoeae infections in the absence of cefixime is to use ceftriaxone," says Kimberly Workowski, MD, chief of the guidelines unit in the epidemiology and surveillance branch of the division of STD prevention of the CDC. "Ceftriaxone or the quinolones should be used, except in the known fluoroquinolone-resistant areas where we are not recommending treatment for infection, which are Hawaii, California, Asia, and the Pacific."

Take aim at the STD

Each year, about 650,000 people in the United States are infected with gonorrhea. In 1999, the rate of reported infections was 132.2 per 100,000 persons, a 9.2% increase above 1997 figures.2 Caused by the bacteria Neisseria gonorrhoeae, gonorrhea is considered a "smart" bacteria since it has developed mechanisms to resist other antibiotics, including penicillin. Fluoroquinolones have been top-line treatments since the 1980s, when gonorrhea grew resistant to tetracycline.

When the CDC issued its revised STD guidelines in 2002, it recommended several single dose treatment options for uncomplicated Neisseria gonorrhoeae urogenital infections: cefixime 400 mg orally, ceftriaxone 125 mg intramuscularly, ciprofloxacin 500 mg orally, ofloxacin 400 mg orally, or levofloxacin 250 mg orally.3

The company that manufacturers cefixime, Wyeth Pharmaceuticals in Collegeville, PA, has discontinued manufacturing cefixime (Suprax) tablets in the United States. In October 2002, the company ceased marketing its 200-mg and 400-mg cefixime tablets because of depletion of company inventory. The company’s patent for cefixime expired on Nov. 10, 2002; no other pharmaceutical company manufactures or sells cefixime tablets in the United States, according to the CDC.4

What are the options?

Clinicians in the areas identified as fluoroquinolone-resistant now look to use of ceftriaxone, a third-generation cephalosporin antibiotic marketed as Rocephin by Hoffmann-La Roche, based in Nutley, NJ. Rocephin is available in intramuscular or intravenous formulations. According to the company, adverse clinical effects in adults to the drug occur at levels similar to those of other cephalosporins: diarrhea (2.7%), rash (1.7%), and local reactions (<1%).

Cefixime was a valuable drug in treating gonorrhea because it was available in tablet form, observes Alan Tice, MD, associate professor at the John A. Burns School of Medicine at the University of Hawaii in Honolulu. While ceftriaxone has maintained its effectiveness against the infection, it must be given via injection. Clinicians in fluoroquinolone-resistant areas now will have to have partners of gonorrhea-infected patients come in for a shot, rather than providing pills for them, he notes.

Several clinicians have expressed interest in oral alternatives to cefixime in treatment of gonorrhea, says Workowski. She points to the CDC’s alternative oral regimens, which have been posted on the STD division’s web site, www.cdc.gov/nchstp/dstd. (Click on the link "Oral Alternatives to Cefixime for the Treatment of Uncomplicated Neisseria Gonorrhoeae Urogenital Infections" listed on the opening page.)

For the CDC to recommend a drug for treatment of uncomplicated gonorrhea, it requires two things: The regimen must cure more than 95% of urogenital infections, and studies that document efficacy must have a sufficient sample size so that the lower limit of the confidence interval of the cure rate is above 95%. At the present time, available data do not show that any single-dose oral antimicrobial regimen, other than cefixime or the fluoroquinolones, meet these efficacy criteria for gonococcal urogenital infection, states the CDC.1

Fluoroquinolone-resistant gonorrhea constitutes a substantial proportion of total gonorrhea cases in Hawaii and Southeast Asia; about 14% of gonorrhea cases in Hawaii were classified resistant in 2002.5 Resistance is being noted in other countries as well; preliminary results from the 2002 collection of data in England and Wales show marked increases in resistant strains.6 Antimicrobial susceptibility monitoring should be routinely performed to ensure that current drug regimens continue to be effective, advises the CDC.

"Prevalence varies by location; it remains important that local communities maintain the capacity to perform testing that will guide their gonorrhea treatment recommendations," says Workowski.

References

1. Centers for Disease Control and Prevention. Oral Alternatives to Cefixime for the Treatment of Uncomplicated Neisseria Gonorrhoeae Urogenital Infections. Atlanta; Dec. 17, 2002. Accessed at www.cdc.gov/std/treatment/Cefixime.htm.

2. Centers for Disease Control and Prevention. Gonorrhea. Atlanta; May 2001. Accessed at www.cdc.gov/nchstp/dstd/Fact_Sheets/FactsGonorrhea.htm.

3. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines 2002. MMWR 2002; 51(RR-6):1-80.

4. Notice to readers: Discontinuation of cefixime tablets — United States. MMWR 2002; 51:1,052.

5. Chase M. Some strains of gonorrhea resist Cipro. Wall Street Journal, March 5, 2002:B5.

6. Dramatic increase in ciprofloxacin-resistant gonorrhoea in England and Wales. CDR Weekly 2003; 13(15). Accessed at www.phls.org.uk/publications/cdr/pages/news.html#grasp.