Literature Commentary by Dr. John G. Bartlett: Sexually Transmitted Infections, January 2008

John G. Bartlett, MD


January 24, 2008

Fluoroquinolone Resistance in Gonococcal Infections and Treatment Options

Centers for Disease Control and Prevention (CDC). Update to CDC's Sexually Transmitted Diseases Treatment Guidelines, 2006: Fluoroquinolones no longer recommended for treatment of gonococcal infections. MMWR Morb Mortal Wkly Rep. 2007;56:332-336. The CDC has announced that fluoroquinolones are no longer recommended for the treatment of uncomplicated gonorrhea.

Methods: This decision is made on the basis of the CDC-sponsored sentinel surveillance system that includes approximately 6000 gonococcal (ie, Neisseria gonorrhoeae) isolates from infected men attending 26-30 sexually transmitted disease (STD) clinics in the United States.

Results: The experience in terms of sensitivity testing to ciprofloxacin is summarized in Table 1 , which indicates sharp increases in resistance to the fluoroquinolone ciprofloxacin in recent years. As noted in the footnote to the table, the rates are particularly high in the category of men who have sex with men. There have also been some substantial geographic differences. Cities with rates exceeding 20% resistance include Honolulu, Hawaii; Long Beach, Orange County, San Diego, and San Francisco, California; Seattle, Washington; and Philadelphia, Pennsylvania. Cities with rates below 3% include Denver, Colorado; Phoenix, Arizona; Chicago, Illinois; Cleveland, Ohio; Minneapolis, Minnesota; Baltimore, Maryland; and Birmingham, Alabama.

Recommendations: On the basis of these observations, the CDC no longer recommends fluoroquinolones for the treatment of gonococcal infections. The result is the following recommendation for treatment of urogenital and anorectal gonorrhea: ceftriaxone 125 mg intramuscularly (IM). Alternative antimicrobial regimens include:

  • Cefixime, single dose of 400 mg once daily. However, the 400-mg tablet of cefixime is no longer available in the United States so that the only available formulation is a suspension.

  • Single IM dose of ceftizoxime 500 mg, cefoxitin 2 g with probenecid 1 g orally, or cefotaxime 500 mg: These cephalosporin regimens do not offer an advantage over ceftriaxone.

  • Spectinomycin 2 g as a single IM dose. However, spectinomycin is no longer available in the United States.

  • Azithromycin 2 g as a single oral dose. However, there are concerns about an increase in the minimum inhibitory concentration since 1999, and there are continuing concerns about gastrointestinal tolerance and the cost of this drug.

  • Cefpodoxime 400 mg or cefuroxime axetil 1 g as single oral doses. "Some evidence" suggests efficacy.

In regard to follow-up, no test of cure is recommended for patients treated with recommended regimens. However, patients with persistent symptoms or recurrent infections should have cultures and susceptibility testing. Treatment failures and resistant isolates should be reported to the CDC at (404) 639-8373.

Comment: This development presents a dilemma for many involved in the management of gonococcal infections. In essence, the only oral treatment that remains is cefixime, which is only available as a suspension. The only recommended treatment still available for the patient with beta-lactam hypersensitivity is spectinomycin, which is simply not available in the United States. It is possible that oral fluoroquinolones could be used in those cities that report a very low prevalence of fluoroquinolone resistance, particularly in women and heterosexual men, but it is probably best done in consultation with authorities in the field, including local health departments.

Wang SA, Harvey AB, Connor SM, et al. Antimicrobial resistance for Neisseria gonorrhoeae in the United States, 1988 to 2003: The spread of fluoroquinolone resistance. Ann Intern Med. 2007;147:81-88. The purpose is to report the prevalence of antibiotic resistance by N gonorrhoeae from 1988 to 2003.

Methods: The analysis is based on a total of 82,064 episodes of gonococcal urethritis in patients seen at STD clinics in 37 cities.

Results: The average age of the patients was 26 years, and 74% were black. The percentage treated with fluoroquinolones increased from 0% in 1988 to 42% in 2003. The percentage resistant to penicillin during this time reached a peak of 19.6% in 1991 and then decreased to 6.5% in 2003. Other observations regarding the in-vitro sensitivity test results with different antimicrobials are shown in Table 2 .

Conclusions: The authors concluded that penicillin resistance is decreasing and that fluoroquinolone resistance is increasing, trends that reflect changing antimicrobial usage patterns for treating gonorrhea.

Comment: This report was published in the Annals of Internal Medicine in July 2007 and included results through 2003, but it was clearly upstaged by the more recent resistance data for fluoroquinolones through 2006 published in the April 13, 2007 edition of MMWR, discussed above. However, this article provides some additional data on trends in treatment and some substantial information about activity of various drugs.


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