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Antimicrobial Resistance and Neisseria gonorrhoeae

• General Information
• Surveillance
• Trends
• Challenges
• Laboratory Issues
• CDC Role

Antimicrobial resistance in N. gonorrhoeae remains an important challenge to controlling gonorrhea; gonococcal strains may be resistant to penicillins, tetracyclines, spectinomycin, and fluoroquinolones. Resistance to CDC-recommended doses of ciprofloxacin and ofloxacin exceeds 40% in some Asian countries (World Health Organization (WHO) Western Pacific Region Gonococcal Antimicrobial Susceptibility Programme (GASP) Report- 2000. Commun Dis Intell 2001; 25:274-277).

Fluoroquinolone-resistant strains of N. gonorrhoeae have also been reported in the United States and Canada. The proportion of gonococcal isolates in Hawaii that are fluoroquinolone-resistant currently exceeds 13% and increasing numbers of resistant strains have been identified in the continental United States (Gonococcal Isolate Surveillance Project (GISP) Annual Report - 2003).

Antimicrobial resistance in N. gonorrhoeae occurs as plasmid-mediated resistance to penicillin and tetracycline, and chromosomally mediated resistance to penicillins, tetracyclines, spectinomycin, and fluoroquinolones.

Surveillance for antimicrobial resistance in N. gonorrhoeae in the United States is conducted through the Gonococcal Isolate Surveillance Project (GISP). The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 to monitor trends in antimicrobial susceptibilities of strains of N. gonorrhoeae in the United States and to establish a rational basis for the selection of gonococcal therapies. Approximately 26 cities participate in GISP. Data from this project have been reported and used to revise the CDC's STD Treatment Guidelines in 1989, 1993, 1998, and 2002.

View GISP Annual Reports

Antimicrobial resistance remains an important consideration in the treatment of gonorrhea. Overall, 16.4%of isolates collected in  2003 by GISP were resistant to penicillin, tetracycline, or both. The percentage of GISP isolates that were penicillinase-producing Neisseria gonorrhoeae (PPNG) declined from a peak of 11.0% in 1991 to 1.0% in 2003. In contrast, the percentage of isolates with chromosomally mediated resistance to penicillin (PenR) had increased from 0.5% in 1988 to 5.7% in 1999 and then declined to 1.3% in 2003. The prevalence of chromosomally mediated tetracycline resistance (TetR) decreased every year since 1995, until 2002. when it slightly increased.  In 2003 there was another slight increase to 6.2% . The prevalence of isolates with chromosomally mediated resistance to penicillin and tetracycline (CMRNG) increased from  3.0% in 1989 to to a peak of 8.7% in 1997 and declined to 3.8% in 2003.

Resistance to ciprofloxacin was first identified in GISP in 1991. From 1991 to 1998, fewer than 9 ciprofloxacin-resistant isolates were identified each year and such isolates were identified in only a few GISP clinics. In 2000, similar to 1999, 19 (0.4%) ciprofloxacin-resistant GISP isolates were identified in 7 of the 25 GISP clinics. In 2001, 38 (0.7%) ciprofloxacin-resistant GISP isolates were identified in 6 clinics.   Two hundred seventy (4.1%) of GISP isolates were resistant to ciprofloxacin (MICs >1.0 g/ml) in 2003, which was two times the proportion identified in 2002 (2.2%, 116/5367).  Ciprofloxacin-resistant isolates were identified in 70% (21/30) sentinel sites in 2003. 

In 2003, no GISP isolates had decreased susceptibility to cefixime or ceftriaxone. The proportion of GISP isolates demonstrating decreased susceptibility to ceftriaxone or cefixime has remained very low over time. To date, no cephalosporin resistance has been identified in GISP. However, it was notable that three of the four isolates with decreased susceptibility to cefixime were also resistant to penicillin, tetracycline, and ciprofloxacin; such multi-drug resistance in combination with decreased susceptibility to cefixime has rarely been identified in the United States (Wang SA, Lee MV, Iverson CJ, O'Connor N, Ohye RG, Hale JA, Knapp JS, Effler PV, Weinstock HS. Multi-drug resistant Neisseria gonorrhoeae with decreased susceptibility to cefixime, Hawaii 2001. [Abstract] International Conference on Emerging Infectious Diseases, Atlanta, Georgia, March 25, 2002.) [Note: no NCCLS criteria currently exist for resistance of N. gonorrhoeae to cephalosporins].

The proportion of GISP isolates demonstrating elevated minimum inhibitory concentrations (MICs) to azithromycin has been increasing since GISP began monitoring azithromycin susceptibility in 1992. In 1992, 0.9% of GISP isolates had azithromycin MIC 0.5 µg/ml compared with 2.2% in 2003. In 1992, there were no isolates with azithromycin MIC 1.0 µg/ml, but in 2003 there were 26 such isolates. [Note: no NCCLS criteria currently exist for susceptibility or resistance of N. gonorrhoeae to azithromycin].

Major challenges to monitoring antimicrobial resistance of N. gonorrhoeae include substantial declines in the use of gonorrhea culture for testing and declines in the number of laboratories performing gonorrhea susceptibility testing. There has been a proliferation of non-culture diagnostic testing for gonorrhea. In many clinical settings, non-culture testing has completely replaced testing using culture. Currently, susceptibility testing can only be performed on N. gonorrhoeae growing in culture. Technology that allows susceptibility testing from non-culture specimens is needed. Research into determining mechanisms of resistance for the newer antimicrobials and for determining the upper limits of resistance conferred by currently recognized mechanisms of resistance to fluoroquinolones is ongoing.

Research into determining mechanisms of resistance for the newer antimicrobials and for determining the upper limits of resistance conferred by currently recognized mechanisms of resistance to fluoroquinolones is ongoing.

CDC conducts national surveillance for antimicrobial resistance in N. gonorrhoeae via GISP and performs outbreak investigations of resistant gonococcal infections as needed. CDC also performs laboratory confirmation for clinicians who identify or suspect antimicrobial resistance in patients with gonorrhea. CDC publishes updated STD Treatment Guidelines on a regular basis to guide use of appropriate and effective antimicrobial therapy for gonorrhea and other STD treatment.