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From the MMWR
January 2001

Fluoroquinolone-Resistance in Neisseria gonorrhoeae, Hawaii, 1999, and Decreased Susceptibility to Azithromycin in N. gonorrhoeae, Missouri, 1999

Author Affiliations

Copyright 2001 American Medical Association. All Rights Reserved. Applicable FARS/DFARS Restrictions Apply to Government Use.2001

Arch Dermatol. 2001;137(1):106-107. doi:10-1001/pubs.Arch Dermatol.-ISSN-0003-987x-137-1-dmm00006

IN 1999, 360,076 cases of gonorrhea were reported in the United States.1 Gonorrhea is a major cause of pelvic inflammatory disease, often leadingto ectopic pregnancy and infertility, and it can facilitate human immunodeficiencyvirus (HIV) transmission.2 During the 1980s, resistance to penicillinand tetracycline among gonococcal isolates became widespread; as a result,CDC recommended that other antimicrobial agents be used to treat gonorrhea.This report summarizes investigations of an increase in fluoroquinolone-resistant Neisseria gonorrhoeae in Hawaii and of a cluster of N. gonorrhoeae infections with decreased susceptibilityto azithromycin in Missouri.

N. gonorrhoeae With Fluoroquinolone-Resistance, Hawaii

The susceptibility of N. gonorrhoeae to ciprofloxacinis used to assess susceptibility to all equivalent fluoroquinolone antimicrobials.The Hawaii Department of Health State Laboratory (HSL) routinely performsantimicrobial susceptibility testing on all gonococcal isolates identifiedby culture. HSL also submits gonococcal isolates from the Diamond Head HealthCenter STD and HIV Clinic in Honolulu, Hawaii, to the Gonococcal Isolate SurveillanceProject (GISP), a CDC-sponsored sentinel surveillance system that monitorsantimicrobial resistance of N. gonorrhoeae. The 26sexually transmitted disease (STD) clinics in the United States that participatein GISP collect male urethral gonococcal cultures and submit them to one offive regional GISP laboratories for antimicrobial susceptibility testing.

An increase in the number of ciprofloxacin-resistant (CipR)* gonococcalisolates submitted by HSL to CDC for reference characterization in 19993 prompted CDC and the Hawaii Department of Health (HDH) to initiatean investigation in September 1999. Military, public, and private laboratorieswere contacted to ascertain routine gonorrhea testing methods (culture versusnonculture). In 1998, 507 gonorrhea cases were reported to HDH. Of these,256 (50%) were diagnosed by culture and underwent antimicrobial susceptibilitytesting at HSL. Antimicrobial susceptibility testing records of gonococcalisolates originating in Hawaii from HSL, GISP, and CDC were reviewed to identifyCipR gonococcal isolates and determine their prevalence in Hawaii.

From January 1990 through September 1999, 105 gonococcal isolates wereidentified that were CipR (n = 48) or had intermediate resistance to ciprofloxacin(CipI)† (n = 57). For CipR isolates, the median ciprofloxacin minimalinhibitory concentration (MIC) was 2.0 µg/mL (range: 1.0–16.0µg/mL). The percentage of gonococcal isolates in Hawaii that were CipRincreased from 1.4% (four of 290) in 1997 to 9.5% (22 of 231) in 1999 (Figure).

Of the 105 patients with CipR/CipI gonorrhea, sex was known for 97;medical records were available for 81. The median age was 30 years (range:1653 years), and 68 (70%) were male. Of 79 with reported race/ethnicity, 42(53%) were Asians/Pacific Islanders, and 20 (25%) were white. The median numberof reported sexual partners during the preceding 30 days was one (range: 0–3).Five (9%) of 55 persons identified themselves as homosexual or bisexual. Nine(12%) of 73 reported antimicrobial use (fluoroquinolone use was reported byone patient) during the 30 days before diagnosis of gonorrhea. Thirty (48%)of 62 denied foreign travel during the 30 days before diagnosis or havinga sex partner with a similar history; 72 (91%) of 79 were treated with ceftriaxoneor cefixime for their gonorrhea.

Of 75 CipR/CipI isolates, 48 (64%) were resistant to penicillin; 28(37%) were penicillinase-producing N. gonorrhoeae.In addition, 33 (44%) were resistant to tetracycline; one had plasmid-mediatedtetracycline resistance. Among isolates tested for susceptibility to otherantimicrobial agents, no evidence was found of decreased susceptibility toceftriaxone, cefixime, or azithromycin, or resistance to spectinomycin.

N. gonorrhoeae With Decreased Susceptibilityto Azithromycin, Kansas City, Missouri

During March–December 1999, GISP identified a cluster of 12 menwith gonorrhea who had decreased susceptibility to azithromycin (AziDS)§. The patients were seen at the Kansas City, Missouri STD clinic.In February 2000, CDC, the Missouri Department of Health and the Kansas CityHealth Department investigated this cluster. Medical records of the 12 patientswere reviewed. The median age was 33 years (range: 23–44 years), and10 were black. Six reported sex with a commercial sex worker, and all 12 deniedsexual contact with other men. Two were HIV infected. Two reported antimicrobialuse during the 30 days before diagnosis. All 12 were treated with cefixime.

The median MIC for azithromycin was 2.0 µg/mL (range: 1.0–4.0µg/mL). Preliminary laboratory data, including antimicrobial susceptibilityresults, auxotype, serovar, and Lip subtype,4 suggest the gonococcalstrains were identical among the 12 patients. All isolates were susceptibleto ceftriaxone, cefixime, spectinomycin, ciprofloxacin, and penicillin. Elevenof the gonococcal isolates had intermediate resistance to tetracycline (MIC= 1.0 µg/mL); the remaining isolate was resistant to tetracycline (MIC= 2.0 µg/mL) but was within testing variability of the results for theother 11.

Reported by:

R Ohye, MS, V Lee, MS, P Whiticar, MA, P Effler, MD, Hawaii Dept ofHealth; H Domen, MS, Hawaii Dept of Health State Laboratory. G Hoff, PhD,J Joyce, R Archer, MD, Kansas City Health Dept, Kansas City; M Hayes, MissouriDept of Health. J Hale, MS, K Holmes, MD, Seattle GISP Regional Laboratory,Univ of Washington, Seattle. L Doyle, MASCP, G Procop, MD, Cleveland GISPRegional Laboratory, Cleveland Clinic Foundation, Cleveland, Ohio. Epidemiologyand Surveillance Br, Div of STD Prevention, National Center for HIV, STD andTB Prevention; Bacterial STD Br, Div of AIDS, STD and TB Laboratory Research,National Center for Infectious Diseases; and EIS officers, CDC.

Editorial Note:

Antimicrobial resistance is an ongoing challenge for gonorrhea treatmentand control. These investigations highlight an increased prevalence of fluoroquinolone-resistantgonorrhea in Hawaii and the emergence in Kansas City of the first reportedcluster of patients with AziDS gonorrhea. These reports are limited to describingdata routinely documented in medical records. Interviews with the patientsand prospective data collection at STD clinics in both areas will providedetailed information on risk factors (e.g., recent travel, recent antimicrobialuse, and contact with commercial sex workers).

CDC recommendations for gonorrhea therapy include use of either of twofluoroquinolone antimicrobials (ciprofloxacin or ofloxacin) because they areinexpensive, single-dose, oral medications.5 Fluoroquinolones areused widely in the United States to treat gonorrhea. Although infections withfluoroquinolone-resistant N. gonorrhoeae are endemicin many Asian countries,6 reports have documented only sporadicisolation of these strains in the United States.1 Excluding Hawaii,0.2% of GISP isolates in 1999 were resistant to fluoroquinolones.1Fluoroquinolone-resistant N. gonorrhoeae were firstreported in the continental United States in 1995 in eight patients in Washingtonand one in Colorado.7

HDH and CDC recommend clinicians in Hawaii no longer use fluoroquinoloneantimicrobials to treat gonorrhea. Absence of foreign travel among 48% ofpatients with CipR/CipI gonorrhea or their reported sex partners suggestsCipR N. gonorrhoeae are being spread endemicallyin Hawaii. Therefore, for patients with gonorrhea in the United States, travelhistory, including sex partner travel history, should be obtained. If patientsor their sex partners are likely to have acquired gonococcal infections inHawaii, the Pacific Islands, or Asia, they should not be treated with fluoroquinoloneantimicrobials; instead, ceftriaxone or cefixime should be used. For thoseunable to tolerate a cephalosporin, spectinomycin should be used.

AziDS gonococcal isolates rarely have been reported in the United Statesor worldwide.8-10 Azithromycin is used widely to treat many community-acquiredinfections in the United States. In addition, a 1 g dose of azithromycin isrecommended by CDC to treat Chlamydia trachomatisinfections.5 However, this dose is inadequate to treat gonorrhea.Although a 2 g dose of azithromycin is approved for gonorrhea therapy by theU.S. Food and Drug Administration, CDC does not recommend routine treatmentof gonorrhea infections with azithromycin because of cost and gastrointestinalintolerance at this dose.5

N. gonorrhoeae must be grown in culture forantimicrobial susceptibility testing to be performed. The increasingly widespreaduse of nonculture methods for gonorrhea diagnosis is a major challenge tomonitoring antimicrobial resistance in N. gonorrhoeae.The changes in antimicrobial resistance patterns described in this reportwere identified only because culture was used as the diagnostic testing methodin these sites and because susceptibilities were being measured through GISPfor Kansas City. HSL is one of the few state public health laboratories performingantimicrobial susceptibility testing on all gonococcal isolates identifiedby culture.

Clinicians who suspect or identify a N. gonorrhoeae infection treatment failure should submit a gonococcal culture specimento the local health laboratory for susceptibility testing. CDC requests reportsof treatment failures or resistant gonococcal isolates from clinicians orlaboratories (National Center for HIV, STD and TB Prevention, Division ofSTD Prevention, telephone [404] 639-8373). CDC recommends that local healthlaboratories with the capacity to perform antimicrobial susceptibility testingon N. gonorrhoeae isolates routinely test for susceptibilityto antimicrobials used locally for gonorrhea treatment (e.g., a fluoroquinolone,cefixime or ceftriaxone, azithromycin, and spectinomycin). Gonococcal isolatesresistant to these classes of antimicrobials can be forwarded to CDC's NeisseriaReference Laboratory (telephone [404] 639-2134) for confirmation and furtherevaluation.

MMWR. 2000;49:833-837.

1 figure and 10 references omitted.

*Resistance to ciprofloxacin is defined by the National Committee onClinical Laboratory Standards as a minimal inhibitory concentration of ≥1.0µg/mL by agar dilution or disk diffusion zone size of ≤27 mm.

†Intermediate resistance to ciprofloxacin is defined by NationalCommittee on Clinical Laboratory Standards as minimum inhibiting concentration= 0.125–0.5 µg/mL by agar dilution or a disk diffusion zone sizeof 28–35 mm.

§Decreased susceptibility to azithromycin was defined for thisinvestigation as MIC of ≥1.0 µg/mL. No National Committee on ClinicalLaboratory Standards criteria exist for decreased susceptibility or resistanceto azithromycin for N. gonorrhoeae.