1. Rapid Emergence of Gonococcal Fluoroquinolone Resistance in Men Who Have Sex with Men in King County, WA WLH Whittington MR Golden KK Winterscheid SA Wang KK Holmes HH Handsfield Department of Medicine, University of Washington, Public Health--Seattle & King County & Centers for Disease Control

2. Background  Effective gonorrhea therapy reduces disease spread by reducing duration of infection  Fluoroquinolone gonococcal resistance has been reported in the Pacific rim, including Hawaii & California  Therapy choices limited by discontinuation by the manufacturer of adult dosage cefixime  In King County, from 1993-2001, prevalence of fluoroquinolone resistance was consistently <1%

3. Objectives  Assess trends in fluoroquinolone resistance in King County, WA  Describe contemporary outbreak caused by fluoroquinolone resistant gonococci

4. Methods  Isolates from private and public clinical laboratories in King County (Schwebke et. al.)  Antimicrobial susceptibilities determined by agar dilution tests (NCCLS)  For assessment of contemporary outbreak, disk diffusion tests (NCCLS) performed immediately

5. Methods (con’t)  Fluoroquinolone resistance defined by an agar dilution MIC  1  g ciprofloxacin/ml  Gonococcal phenotypes said to differ if auxotype differed or susceptibilities differed by >2 dilutions to >2 classes of antimicrobials  Patients & isolate characteristics compared between those with ciprofloxacin resistant and susceptible infections using parametric and non-parametric tests; logistic regression utilized to control for covariates

6. Proportion of infections caused by ciprofloxacin resistant* gonococci 1993-2002 isolates (1208) (996) (726) (624) (815) * By criterion of NCCLS

7. Fluoroquinolone Resistance 1993-2002  Small outbreak during 1995 associated with commercial sex work (Whittington et. al.)  Excess cases during 2002 among men, often MSM However, no additional cases detected by screening of 240 gonococcal isolates from October 2003 through April 2004 However, no additional cases detected by screening of 240 gonococcal isolates from October 2003 through April 2004

8. Proportion of infections caused by ciprofloxacin resistant* gonococci by quarter, 2003 *By criterion of NCCLS History suggestive of acquisition elsewhere

9. Resistance by gender, source of care and sexual preference % (n/total) % (n/total) Source of care STD Clinic 12% (21/171) STD Clinic 12% (21/171) Other 6% (7/121) Other 6% (7/121)Gender Male 12% (27/222)** Male 12% (27/222)** Female 1% (1/70) Female 1% (1/70) Sexual preference* Heterosexual 3% (2/76) Heterosexual 3% (2/76) MSM 22% (19/85)** MSM 22% (19/85)** *STD Clinic patients only **P<0.05

10. Characteristics of infecting gonococci by fluoroquinolone resistance Resistant Susceptible Resistant Susceptible (n=28) (n=264) (n=28) (n=264) Different Phenotypes* 3 ~20 Median (range) MIC (  g/ml) Penicillin G 1.0 (0.25-2.0)** 0.25 (0.03-2.0) Penicillin G 1.0 (0.25-2.0)** 0.25 (0.03-2.0) Tetracycline HCl 1.0 (0.5-4.0)** 0.5 (0.06-4) Tetracycline HCl 1.0 (0.5-4.0)** 0.5 (0.06-4) Erythromycin 1.0 (0.5-2.0)** 0.5 (0.008-16.0) Erythromycin 1.0 (0.5-2.0)** 0.5 (0.008-16.0) Azithromycin 0.125 (0.06-0.25)** 0.06 (0.008-2.0) Azithromycin 0.125 (0.06-0.25)** 0.06 (0.008-2.0) *Based on antibiogram and auxotype; PFGE pending; 1 cipR phenotype dominant **P<0.05

11. Limitations  Based only on those infections from which isolates were received Previously shown that samples were representative of all reported cases Previously shown that samples were representative of all reported cases However, recent use of NAAT by many providers introduces potential for bias, e.g. women may be underrepresented However, recent use of NAAT by many providers introduces potential for bias, e.g. women may be underrepresented

12. Summary & Significance  Spread was rapid—from undetected to 16% of isolates in < 6 months  Most (86%) resistant isolates had ciprofloxacin MICs >4  g/ml Failure rates of ~50% after ciprofloxacin therapy (Aplasca et. al.) Treatment failure was documented in 4 local patients  Spread was most efficient among MSM Due to behaviors or selective advantage of resistant strains (ciprofloxacin resistance or macrolide resistance as marker of resistance to killing by fecal lipids?)

13. Intervention  Immediate disk diffusion testing permitted timely identification of this problem  Local treatment recommendations changed in November 2003 to include cefpodoxime 400mg P.O. plus doxycycline or azithromycin; fluoroquinolones no longer recommended

14. Addendum  During January-February 2004, prevalence of fluoroquinolone resistant gonococci remained high (20%, 20/98)  Resistant isolates were recovered from 2 additional women during this period

15. Acknowledgements  Sarah Lam for performance of disk diffusion susceptibility tests  Olusegnu Soge for performance of PFGE  Financial support from the CDC and NIAID

17. Disk diffusion antimicrobial susceptibilities: cefpodoxime and cefixime (n=220) Cefpodoxime (mm) Cefixime r=0.78

18. Selection of Gonorrhea Therapy