Factors Related to Increasing Prevalence of Resistance to Ciprofloxacin and Other Antimicrobial Drugs in Neisseria gonorrhoeae, United States

Edward Goldstein

, Robert D. Kirkcaldy, David Reshef, Stuart Berman, Hillard Weinstock, Pardis Sabeti, Carlos Del Rio, Geraldine Hall, Edward W. Hook, and Marc Lipsitch

Author affiliations: Harvard School of Public Health, Boston, Massachusetts, USA (E. Goldstein, M. Lipsitch); Centers for Disease Control and Prevention, Atlanta, Georgia, USA (R.D. Kirkcaldy, S. Berman, H. Weinstock); Oxford University, Oxford, UK (D. Reshef); Harvard University, Cambridge, Massachusetts, USA (P. Sabeti); Emory University, Atlanta (C. Del Rio); Cleveland Clinic, Cleveland, Ohio, USA (G. Hall); University of Alabama at Birmingham, Birmingham, Alabama, USA (E.W. Hook); and Jefferson County Department of Health, Birmingham (E.W. Hook)

Abstract

Using data from the Gonococcal Isolate Surveillance Project, we studied changes in ciprofloxacin resistance in Neisseria gonorrhoeae isolates in the United States during 2002–2007. Compared with prevalence in heterosexual men, prevalence of ciprofloxacin-resistant N. gonorrhoeae infections showed a more pronounced increase in men who have sex with men (MSM), particularly through an increase in prevalence of strains also resistant to tetracycline and penicillin. Moreover, that multidrug resistance profile among MSM was negatively associated with recent travel. Across the surveillance project sites, first appearance of ciprofloxacin resistance in heterosexual men was positively correlated with such resistance for MSM. The increase in prevalence of ciprofloxacin resistance may have been facilitated by use of fluoroquinolones for treating gonorrhea and other conditions. The prominence of multidrug resistance suggests that using other classes of antimicrobial drugs for purposes other than treating gonorrhea helped increase the prevalence of ciprofloxacin-resistant strains that are also resistant to those drugs.

Gonorrhea is the second most frequently reported communicable disease in the United States (1). Following implementation of a national gonorrhea control program in the mid-1970s, gonorrhea incidence in the Unites States declined by 74.3% from 1975 to 1997 (2). However, during this time, the treatment and control of gonorrhea have been complicated by the appearance and spread of antimicrobial drug resistance in Neisseria gonorrhoeae (3,4). Cephalosporins and fluoroquinolones became recommended for treating gonorrhea in the United States in 1993 (5), prompted by the rise in resistance to penicillins and tetracyclines, the antimicrobial agents previously recommended for treatment. In the past decade, several countries reported a sharp rise in the proportion of N. gonorrhoeae strains resistant to fluoroquinolones (QRNG) (1,4,6–9). Increasing QRNG prevalence in the United States led to a series of changes in treatment recommendations away from fluoroquinolones. In 2002, the Centers for Disease Control and Prevention (CDC; Atlanta, Georgia, USA) recommended that cephalosporins be used instead of fluoroquinolones as first-line treatment for gonorrhea acquired in Hawaii or California (8); in 2004, fluoroquinolones were no longer recommended as a first line of treatment for infected men who have sex with men (MSM) and, as of 2007, fluoroquinolones were no longer recommended, and cephalosporins were the only recommended class of drugs for treatment of gonococcal infections in the United States (10). As treatment failures for oral cephalosporins are documented in Asia (3,11,12), and strains with reduced susceptibility to cephalosporins have begun to appear in the West, including the United States (3,13,14), the origins and causes of increased drug resistance in N. gonorrhoeae need to be understood in order to improve control measures for emerging resistant strains and thereby maintain the utility of the few existing antimicrobial drug options for treatment of gonorrhea.
We examined several hypotheses to explain the increased prevalence of QRNG during 2002–2007, with the objective of identifying principles that may be informative for predicting and preventing the spread of resistance to cephalosporins or other drug classes. We considered the role of travel as a contributing factor for the growth of resistance, in heterosexual men and MSM. Having observed a difference in travel patterns between men of differing sexual orientation, we hypothesized about a potential role that multidrug resistance may play in the propagation of that resistance profile. Additionally, we studied the association between the times of first appearance of ciprofloxacin resistance in heterosexual men and in MSM in several different Gonococcal Isolate Surveillance Project (GISP) sites, examining the possibility that resistance spread in persons of one sexual orientation led to the appearance of resistance in persons of another sexual orientation.

Medscape CME articles
Volume 18, Number 8–August 2012

Factors Related to Increasing Prevalence of Resistance to Ciprofloxacin and Other Antimicrobial Drugs in Neisseria gonorrhoeae, United States

MEDSCAPE CME

Medscape, LLC is pleased to provide online continuing medical education (CME) for this journal article, allowing clinicians the opportunity to earn CME credit.
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All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at www.medscape.org/journal/eid ; (4) view/print certificate.

Release date: July 16, 2012; Expiration date: July 16, 2013

Learning Objectives

Upon completion of this activity, participants will be able to:
• Describe overall patterns of drug resistance stratified by sexual orientation, based on an analysis of data from GISP
• Describe the association of recent travel with drug resistance in MSM and heterosexuals, based on an analysis of data from GISP
• Describe the first appearance of drug resistance in heterosexuals and MSM, based on an analysis of data from GISP.

CME Editor

Carol E. Snarey, MA, Technical Writer/Editor, Emerging Infectious Diseases. Disclosure: Carol E. Snarey, MA, has disclosed no relevant financial relationships.

CME AUTHOR

Laurie Barclay, MD, freelance writer and reviewer, Medscape, LLC. Disclosure: Laurie Barclay, MD, has disclosed no relevant financial relationships.

AUTHORS

Disclosures: Edward Goldstein, PhD; Robert D. Kirkcaldy, MD, MPH; David Reshef; Stuart Berman, MD; Hillard Weinstock, MD, MPH; Pardis Sabeti, MD, DPhil; Geraldine Hall, PhD; and Marc Lipsitch, PhD, have disclosed no relevant financial relationships. Carlos Del Rio, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Gilead Sciences; received grants for clinical research from Merck and Co. Edward W. Hook, MD, has disclosed the following relevant financial relationships: served as an advisor or consultant for Cempra; served as a speaker or a member of a speakers bureau for Becton Dickinson; received grants for clinical research from Becton Dickinson, Cepheid, Roche Molecular, Gen-Probe Inc., Cempra, Siemens, GlaxoSmithKline; acted as a book editor and received royalties from McGraw Hill.