Gonococcal Isolate Surveillance Project (GISP) Neisseria Gonorrhoeae (GC) culture specimen streaking

Neisseria gonorrhoeae Gonorrhea is a bacterial STD Sequelae of untreated infection include Pelvic inflammatory disease Infertility Chronic pelvic pain Increases risk of HIV transmission and acquisition Gonorrhea is second most frequently reported communicable disease in the U.S.

Gonococcal Resistance to Antimicrobial Agents 1970’s – penicillin- and tetracycline- resistant N. gonorrhoeae appeared, leading to abandonment of these therapies for gonorrhea 1990’s to present – prevalence of fluoroquinolone resistant N. gonorrhoeae (QRNG) has been increasing 2000 - CDC recommends that fluoroquinolones (FQs) no longer be used to treat gonorrhea acquired in Hawaii, Pacific Islands, or Asia; need travel history for all GC patients

Gonoccocal Resistance to Antimicrobial Agents (continued) 2002 - CDC recommends that use of FQs in California and in other areas with increased QRNG may be inadvisable 2004 – Due to increases in QRNG, CDC recommends that FQs no longer be used to treat gonorrhea Current CDC recommended primary therapies for GC are: Cefixime, Ceftriaxone, Ciprofloxacin, Ofloxacin, Levofloxacin PLUS, IF CHLAMYDIAL INFECTION IS NOT RULED OUT Azithromycin OR Doxycycline

The Gonococcal Isolate Surveillance Project (GISP) Increasing rates of gonorrhea and ciprofloxacin resistance pose challenges to disease control. GISP is the national sentinel surveillance system established in 1986 by CDC. Consists of public STD clinics in 30 US cities and 5 regional labs. 25 male gonococcal isolates tested from each site each month. The LA Sentinel Site was established in 2003. It includes 2 high-volume STD clinics with diverse populations, South Health Center and the Los Angeles Gay and Lesbian Center (LAGLC). The Gonoccocal Isolate Surveillance Project (GISP) is an example of how increased surveillance by clinics and labs can impact disease treatment.

Establishing LA as a GISP Site In mid-March 2003, the two STD clinics began collecting urethral cultures from males presenting with expressible urethral discharge characteristic of gonorrhea. Clinics collected demographic, clinical, and client-reported behavioral data. Gonococcal isolates presumptively identified by the LA County Public Health Lab were shipped to the Denver GISP Regional Lab for confirmation and antibiotic susceptibility testing by agar dilution.

GISP — Location of participating clinics and regional laboratories: United States, 2004 Adapted from CDC slides

GISP Percent of Neisseria gonorrhoeae isolates with resistance to ciprofloxacin by sexual behavior, 2001–2004 Adapted from CDC slides

GISP Penicillin and tetracycline resistance among GISP isolates, 2004 Note: PPNG=penicillinase-producing N. gonorrhoeae; TRNG=plasmid-mediated tetracycline-resistant N. gonorrhoeae; PPNG-TRNG=plasmid-mediated penicillin- and tetracycline-resistant N. gonorrhoeae; PenR=chromosomally mediated penicillin resistant N. gonorrhoeae; TetR=chromosomally mediated tetracycline-resistant N. gonorrhoeae; CMRNG=chromosomally mediated penicillin- and tetracycline-resistant N. gonorrhoeae. Adapted from CDC slides

GISP - Percent of Neisseria gonorrhoeae isolates with resistance or intermediate resistance to ciprofloxacin, 1990–2004 Note: Resistant isolates have ciprofloxacin MICs ≥ 1 µg/ml. Isolates with intermediate resistance have ciprofloxacin MICs of 0.125 - 0.5 µg/ml. Susceptibility to ciprofloxacin was first measured in GISP in 1990. Adapted from CDC slides

LA GISP Isolates by Clinic March 2003 – June 2005

Race/Ethnicity of GISP Participants March 2003 – June 2005 N=572

Sexual Orientation of GISP Participants March 2003 – June 2005 Overall, the majority of the gonorrhea positive men were heterosexual (62%). However, when separated by clinic, 96% of men from South Health Center were heterosexual, while 97% of men from LAGLC were either homosexual or bisexual. N=572

Number of Isolates

HIV Status, Positive Cultures and Resistant Isolates Number of Isolates

Resistance and Decreased Antimicrobial Susceptibility Number of Isolates N=572

L.A. GISP Project Total 21% reported non-injection drug use 7% used antibiotics 7% traveled outside CA 1% reported injection drug use 1% was involved in sex work During the 60 days prior to diagnosis of gonorrhea, GISP patients reported the following behaviors.

L.A. GISP TREATMENT FOR GC AND CHL Primary treatment for gonorrhea: Ceftriaxone 250 mg (93%) Primary treatment for chlamydia: Azithromycin 1 g (98%) The antimicrobial agents given to GISP participants are shown here.

Ciprofloxacin-Resistant GC in California Prevalence of cipro-resistant GC in CA >10% in 2002 CA GC Tx Recommendations: Avoid the use of fluoroquinolones (ciprofloxacin, ofloxacin, and levofloxacin) to treat GC in California. Use ceftriaxone 125mg by intramuscular (IM) injection to treat uncomplicated gonococcal infections of the cervix, urethra, and rectum Fluoroquinolones (Cipro) are no longer recommended by the CDC as treatment for GC in CA as of 2002.

The Problem with QRNG Limited availability of a recommended oral treatment regimen for gonorrhea poses practical problems for treating QRNG. Besides the fluoroquinolones, cefixime, whose manufacture was discontinued in 2002, is the only CDC-recommended oral agent for treating gonorrhea. The health departments of California and Washington state have suggested alternative oral treatments (e.g., cefpodoxime 400 mg) that have not yet been evaluated adequately. Cipro was orally administered. The only other oral single dose tx was cefixime, but its production was discontinued in 2002. No other single dose oral antimicrobial regimen meets efficacy and safety criteria. Ceftriaxone 125 mg IM (intramuscular) single dose is the current recommended tx in CA. Cefpodoxime is being researched as an oral alternative for GC tx.

The Challenges of Monitoring Gonococcal Resistance Few labs perform susceptibility testing. Mainly public health labs, yet >60% GC reported from private sector. Absence of culture testing, so no organisms for susceptibility testing. Non-culture tests (amplified tests) rapidly replacing culture. Some health depts no longer have GC culture capacity at all.

The Challenges of Monitoring Gonococcal Resistance (continued) Bias toward over-representation of data from rectal and pharyngeal sources. Culture is the preferred test for these anatomic sites (other tests not recommended). Less data from urethral and endocervical sites due to increased Nucleic Acid Amplification Test usage. Limited sampling of certain populations: military, women, private patients

More Information Clinical Lab Survey Report, 2002 GISP http://www.lapublichealth.org/std/ The "Reports" section contains this and other reports published by the LA County STD Program. GISP http://www.cdc.gov/std/gisp/ Resource website for information on antimicrobial resistant Neisseria gonorrhoeae.