# Presentation: 391201

## Update on Gonococcal Resistance in the United States Susan A. Wang, MD, MPHDivision of STD PreventionNational Center for HIV, STD, and TB Preventionswang3@cdc.govMarch 2004

## The continuing saga: history of antimicrobial resistance in Neisseria gonorrhoeae in the United States

- 1936: sulfanilamide introduced
- 1945: 1/3 of gonorrhea sulfanilamide-resistant; 50,000 units of penicillin becomes therapy of choice
- 1972: therapeutic penicillin dose reaches 4.8 million units
- 1976: PPNG first identified in U.S. patient with recent travel to Southeast Asia

## History -  Part II

- early 1980s: PPNG strains spread in the U.S.;  beta-lactamase testing commonplace
- 1985: widespread tetracycline-resistance among gonococci; CDC recommends that tetracycline not be used for gonorrhea therapy
- 1987: penicillin abandoned; ceftriaxone becomes primary treatment
- 1989: ciprofloxacin (FQ) recommended by CDC
- 1991: QRNG identified in Hawaii

## History -  Part III

- 1998: marked QRNG increase in Hawaii
- 2000: CDC recommends that FQs no longer be used to treat gonorrhea acquired in Hawaii, Pacific Islands, or Asia; need travel hx for all GC pts
- 2002: CDC recommends that use of FQs in California and in other areas with increased QRNG may be inadvisable
- 2002-2004: local QRNG alerts and treatment recommendation changes

## Quinolone Resistance Among Gonococci Elsewhere in the World

- Australia – 8.1%			England & Wales – 9.8%
- China – 92.5%			     	*(GRASP, 2002)*
- Japan – 73.4% 			 Norway - 15%
- Korea – 63.3%				 *(Aavitsland, et al 2002)*
- Phillippines – 57.5%		Canada – 2.1%
- Singapore – 46.5%			 	*(Sarwal, et al, 2001)*
- Vietnam – 46.0%			Israel – 61% 			*(WHO WPR GASP, 2002) **	**	**	**(Dan, et al, 2000)*
*	**	**	**	**	**	*
*	**	**	**	**	**	**	*

## Surveillance for gonococcal resistance in the United States

- National sentinel surveillance
- Local susceptibility surveillance

## The Gonococcal Isolate Surveillance Project (GISP)

- National sentinel surveillance established in 1986 by CDC to monitor trends in antimicrobial susceptibilities of *N. gonorrhoeae*
- Consists of public STD clinics* *in* *26-30 cities and 5 Regional Laboratories
- Every month each clinic submits first 25 male urethral gonococcal isolates to a Regional Laboratory
- Each Regional Lab performs antimicrobial susceptibility testing by agar dilution
- Each clinic also submits patient demographic and clinical data for all submitted isolates  allows us to monitor characteristics of patients with gonorrhea

## Gonococcal Isolate Surveillance Project (GISP)

**Locations of clinics and regional laboratories:  **
**United States, 2003**

- Phoenix

- Albuquerque

- Dallas

- San Diego

- Orange Co.

- Las
-  Vegas

- Portland

- Anchorage

- New

- Orleans

- Honolulu

- San Francisco

- Long Beach

- Minneapolis

- Philadelphia

- Cincinnati

- Baltimore

- St. Louis

- Chicago

- Miami

- Denver

- Atlanta

- Birmingham

- Seattle

- Cleveland

- Birmingham

- Regional Labs

- Atlanta

- Denver

- Seattle

- Cleveland

- Tripler AMC

- Los Angeles

- Greensboro

- Detroit

- Salt Lake
- City

- Oklahoma
- City

## Gonorrhea treatment for GISP participants, 

**1988-2003***

- *2003 data are preliminary.

## Percentage of GISP isolates with intermediate resistance or resistance to ciprofloxacin, 1990-2003*

- *2003 data are preliminary.

## Ciprofloxacin-resistant GISP isolates in the U.S.

**Year****	****  Sentinel Sites****	****	****	****      ****	****     ****	****	****Isolates**
- 1991	   Honolulu						   1
- 1993	   Honolulu					  	   1
- 1994	   Honolulu, San Francisco			   	   	   2
- 1995	   Honolulu, San Francisco, Seattle, Denver	  		   8
- 1996	   Seattle					   	  	   2
- 1997	   Honolulu, San Diego, Portland, Atlanta		   	   	   5
- 1998	   Honolulu, San Francisco, Cincinnati			   	   4
- 1999	   Honolulu, San Francisco, San Diego, Orange Co,
- 		   Seattle, Anchorage, Denver, Cincinnati,
- 		   New Orleans, Fort Bragg				 	 19
- 2000	   Honolulu, San Francisco, San Diego, Orange Co,
- 		   Seattle, Anchorage					 19
- 2001	   Honolulu, San Francisco, San Diego, Orange Co,
- 		   Long Beach, Denver					 38
- 2002	   Honolulu, San Francisco, San Diego, Orange Co,
- 		   Long Beach, Anchorage, Portland, Seattle, Phoenix,
- 		   Minneapolis, Cincinnati, Philadelphia, Miami	              	                116
- 2003*	   Honolulu, Tripler, San Francisco, Los Angeles, San Diego,
- prelim	   Orange Co, Long Beach, Portland, Seattle, Las Vegas,
- 		   Phoenix, Denver, Minneapolis, Chicago, Cincinnati, Cleveland,
- 		   Philadelphia, Baltimore, Dallas, New Orleans, Miami	                259*

## Prevalence of ciprofloxacin-resistant Neisseria gonorrhoeae among tested gonococcal isolates,* and gonorrhea rate, Hawaii, 1993-2003**

- *Includes GISP and non-GISP isolates for every year except 2003.
- **2003 data are preliminary and only GISP data.

## Prevalence of ciprofloxacin-resistant GISP isolates and gonorrhea rate, California, 1993-2003*

- *2003 data are preliminary

## Percent ciprofloxacin-resistant isolates in GISP, excluding Hawaii and California, 1990-2003*

- *2003 data are preliminary.

## Preliminary 2003 GISP Data – QRNG (incomplete)

-     QRNG (all sites)			4.1% (243/5936)
- Orange Co			32.5% (49/151)
- Long Beach			21.5% (17/79)
- San Francisco			19.0% (51/268)
- Los Angeles			13.3% (22/165)
- Honolulu				13.3% (16/120)
- San Diego 			12.1% (26/215)
- Seattle			  	  7.0% (18/258)
- Tripler				  4.2% (1/24)
- Portland				  3.0% (4/132)
- Las Vegas			  2.4% (7/287)

## Preliminary 2003 GISP Data - QRNG

- Minneapolis		2.3% (5/215)
- Phoenix 			2.2% (4/183)
- Chicago			2.1% (6/285)
- Dallas			2.1% (6/288)
- Philadelphia		1.3% (4/316)
- Miami			1.2% (2/164)
- New Orleans 		0.7% (1/152)
- Cincinnati 		0.4% (1/276)
- Denver			0.4% (1/250)
- Baltimore			0.4% (1/289)
- Cleveland			0.3% (1/292)

## GISP QRNG by Sexual Orientation, 2002 and 2003*

- All sites

- Excluding Hawaii and California

- *2003
- data are
- preliminary

## Preliminary Non-GISP QRNG in 2003incomplete

- New Hampshire – 28.6% (6/21)
- Massachusetts – 13.9% (56/402)
- Michigan – 2.9% (17/582)
- New York City – 2.9% (30/1026)
- Indianapolis – 0.4 (2/491)
- Other places where QRNG have been identified: Kansas (1), Maine (1), New Jersey (2), New York (1), Ohio (1), Utah (1)
- In 2002, no health dept susceptibility testing data for 72% of STD programs and limited susceptibility data available for the other 28%

## QRNG clusters in 2003

- New York City *(Reddy, P013)*: ~8% GC cases tested; 13% QRNG among MSM, 2% among MSW and among women
- Massachusetts *(Ratelle, P014)*: ~12% GC cases tested; 11% QRNG among MSM and 2% among MSW
- Michigan *(Macomber, LB10)*: ~4% GC cases tested; 12% QRNG among MSM, 9% among MSW, 2% among women
- Seattle *(Whittington, Tues LB)*:  22% QRNG among MSM and 3% among MSW and women
- Cost-effectiveness model to identify threshold for changing treatment *(Roy, P068)*

## Factors Associated with Acquisition of QRNG(in areas where QRNG is not endemic)

- Residence in or history of recent travel to Asia or the Pacific Islands, Hawaii, California, or other areas with increased QRNG prevalence or sex partner with such history
- Asian and White races
- Heterosexual transmission (England, Norway, Australia, U.S.)
- In 2002-2003, MSM transmission in the U.S.

## GISP Trends for Other Antimicrobials

- In 2002, prevalence of resistance for penicillin was 8.2% and for tetracycline was 14.7%
- No isolates resistant to spectinomycin since 1994
- Proportion of isolates with azithromycin Minimum Inhibitory Concentrations (MICs)  1.0 mg/L increased from 0 in 1992 to 0.6% in 2002
- No isolates with decreased susceptibility to ceftriaxone since 1997 (but trend toward higher MICs).

## GISP Trends for Other Antimicrobials, 

- Multi-drug resistant isolates identified in 2001 in Hawaii and again in 2003 in Los Angeles:  resistant to penicillin, tetracycline, ciprofloxacin; decreased susceptible to cefixime and azithromycin
- these types of isolates identified since 1999 in Japan where cefixime treatment failures have also been reported

## The Challenges of Monitoring Gonococcal Resistance

- Few laboratories performing susceptibility testing
- primarily public health laboratories, yet >60% of GC reported from private sector
- Absence of culture testing so no organism to susceptibility test
- non-culture tests (NAATs) rapidly replacing culture; some health depts no longer have GC culture capacity at all

## The Challenges of Monitoring Gonococcal Resistance

- Bias toward over representation of data from rectal and pharyngeal isolates since only culture has FDA indication for those anatomic sites
- fewer data from urethral and endocervical isolates
- Extremely limited sampling or no sampling of certain populations
- e.g., military, women, private patients

## Summary

- Antimicrobial resistance remains a **key** consideration in the treatment and control  of gonorrhea
- Preliminary 2003 data show QRNG remained endemic in Hawaii and California.  Significant QRNG increases were noted in Seattle, New Hampshire, Massachusetts, New York City, and Michigan, and were identified with increasing frequency elsewhere in the U.S.
- QRNG increases among MSM are a concern
- Significant challenges exist in 2004 for monitoring resistance

## Acknowledgements

- The many GISP collaborators:
- GISP Regional Laboratories (Atlanta, Birmingham, Cleveland, Denver, Seattle):  Laura Doyle, Josephine Ehret, Connie Lenderman, James Thomas, Wil Whittington, Karen Winterscheid, Carlos del Rio, King Holmes, Ned Hook, Frank Judson, Gary Procop
- the 30 GISP Sentinel Sites: lab, clinic, program staff
- Alesia Harvey, Susan Conner
- Health departments performing local susceptibility testing:  Massachusetts, Michigan, New York City, New Hampshire, Hawaii, Indianapolis, Wisconsin, and more...

- _[http://www.cdc.gov/std/gisp/](http://www.cdc.gov/std/gisp/)_
- 	Please report GC treatment failures or identification of resistant GC to CDC (via program consultant or 404 639-8373 or _[swang3@cdc.gov](mailto:swang3@cdc.gov)_).

## Gonorrhea Treatment(from CDC STD Treatment Guidelines, May 10, 2002 MMWR) 

- Cefixime 400 mg
- or
- Ceftriaxone 125 mg IM
- or
- Ciprofloxacin 500 mg or
- Ofloxacin 400 mg or Levofloxacin 250 mg
- [plus, treatment for *Chlamydia trachomatis* infection]
-   * Need to obtain travel history from patients suspected to have gonorrhea. A patient who may have acquired gonorrhea in Asia or Hawaii or the Pacific Islands or whose sex partner(s) may have acquired gonorrhea in those places should NOT be treated with quinolones!  Use of quinolones is probably inadvisable for infections acquired in California and in other areas with increased prevalence of quinolone resistance.

## Treatment of Chlamydia trachomatis infection in GISP participants, 1992-2003*

- For each year, “other” accounted for < 1% and erythromycin accounted for no more than 1% of treatment.  *2003 data are preliminary.

## Observations on QRNG surveillance

- Most QRNG patients have NOT been identified as a result of recognition of treatment failures but through susceptibility testing
- Where QRNG surveillance is taking place, susceptibility data generally represent <15%          of GC cases