Gonococcal Isolate Surveillance Gonococcal Isolate Surveillance Project (GISP)Project (GISP)

Neisseria GonorrhoeaeNeisseria Gonorrhoeae (GC) culture specimen streaking (GC) culture specimen streaking

Neisseria gonorrhoeaeNeisseria gonorrhoeae

Gonorrhea is a bacterial STDGonorrhea is a bacterial STDSequelae of untreated infection includeSequelae of untreated infection include– Pelvic inflammatory disease Pelvic inflammatory disease – InfertilityInfertility– Chronic pelvic painChronic pelvic pain

Increases risk of HIV transmission and Increases risk of HIV transmission and acquisitionacquisitionGonorrhea is second most frequently Gonorrhea is second most frequently reported communicable disease in the reported communicable disease in the U.S.U.S.

Gonococcal Resistance to Gonococcal Resistance to Antimicrobial AgentsAntimicrobial Agents

1970’s – penicillin- and tetracycline- resistant 1970’s – penicillin- and tetracycline- resistant N. N. gonorrhoeae gonorrhoeae appeared, leading to abandonment appeared, leading to abandonment of these therapies for gonorrheaof these therapies for gonorrhea

1990’s to present – prevalence of fluoroquinolone 1990’s to present – prevalence of fluoroquinolone resistant resistant N. gonorrhoeaeN. gonorrhoeae (QRNG) has been (QRNG) has been increasingincreasing

2000 - CDC recommends that fluoroquinolones 2000 - CDC recommends that fluoroquinolones (FQs) no longer be used to treat gonorrhea (FQs) no longer be used to treat gonorrhea acquired in Hawaii, Pacific Islands, or Asia; need acquired in Hawaii, Pacific Islands, or Asia; need travel history for all GC patientstravel history for all GC patients

Gonoccocal Resistance to Gonoccocal Resistance to Antimicrobial AgentsAntimicrobial Agents

(continued)(continued)2002 - CDC recommends that use of FQs in California and 2002 - CDC recommends that use of FQs in California and in other areas with increased QRNG may be inadvisablein other areas with increased QRNG may be inadvisable2004 – Due to increases in QRNG, CDC recommends that 2004 – Due to increases in QRNG, CDC recommends that FQs no longer be used to treat gonorrheaFQs no longer be used to treat gonorrheaCurrent CDCCurrent CDC recommended primary therapies for GC are: recommended primary therapies for GC are:– Cefixime, Ceftriaxone, Ciprofloxacin, Ofloxacin, Cefixime, Ceftriaxone, Ciprofloxacin, Ofloxacin,

LevofloxacinLevofloxacin– PLUS, IF CHLAMYDIAL INFECTION IS NOT RULED PLUS, IF CHLAMYDIAL INFECTION IS NOT RULED

OUTOUTAzithromycin OR DoxycyclineAzithromycin OR Doxycycline

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

The Gonococcal Isolate The Gonococcal Isolate Surveillance Project (GISP)Surveillance Project (GISP)

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

Establishing LA as a GISP Establishing LA as a GISP SiteSite

GISP — Location of participating GISP — Location of participating clinics and regional laboratories: United States, clinics and regional laboratories: United States,

20042004

STD ClinicsClinics and Regional Labs

Birmingham Phoenix

Long Beach Los Angeles

Orange Co. San Diego

San Francisco Denver

Miami

Atlanta

Honolulu

Tripler AMC

Chicago

New Orleans

Baltimore

Detroit Minneapolis

St. Louis Las Vegas

Albuquerque

Greensboro

Cincinnati

Cleveland

Oklahoma City

Portland

Philadelphia

Dallas

Seattle

Adapted from CDC slides Adapted from CDC slides

GISP Percent of GISP Percent of Neisseria gonorrhoeaeNeisseria gonorrhoeae isolates isolates with resistance to ciprofloxacin by sexual behavior, with resistance to ciprofloxacin by sexual behavior,

2001–20042001–2004

Percent Ciprofloxacin Resistant

Heterosexual

Men who have sex with men (MSM)

0

5

10

15

20

25

2001 2002 2003 2004

Adapted from CDC slides Adapted from CDC slides

GISP Penicillin and tetracycline resistance among GISP GISP Penicillin and tetracycline resistance among GISP isolates, 2004isolates, 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.

Susceptible

PPNG

TRNG

PPNG/TRNG

PenR

TetR

CMRNG

84.1%

0.6%

3.4%0.5%1.1%

6.1%

4.3%

Adapted from CDC slides Adapted from CDC slides

GISP - Percent of GISP - Percent of Neisseria gonorrhoeaeNeisseria gonorrhoeae isolates isolates with resistance or intermediate resistance to with resistance or intermediate resistance to

ciprofloxacin, 1990–2004ciprofloxacin, 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.

Percent

Resistance

Intermediate resistance

0.0

2.0

4.0

6.0

8.0

10.0

1990 91 92 93 94 95 96 97 98 99 2000 01 02 03 04

Adapted from CDC slides Adapted from CDC slides

LA GISP Isolates by ClinicLA GISP Isolates by ClinicMarch 2003 – June 2005March 2003 – June 2005

28%

72%

GLC

South HC

N=572N=572

African AmHispanicAmindAsianNaHaw/PIWhiteOther

Race/Ethnicity of GISP Participants

March 2003 – June 2005

N=572

HeterosexualHomosexualBisexual Unknown

Sexual Orientation of GISP Participants

March 2003 – June 2005

N=572

1

74

125137

98 101

27

90

11 1627 22

40

112

0102030405060708090

100110120130140150

<15 15-19

20-24

25-29

30-34

35-44

45-54

55+

Total Resistant

Positive Cultures and Resistant Isolates by Age Los Angeles Sentinel Site

March 2003 – June 2005 N=572, 129

Num

ber

of I

sola

tes

HIV Status, Positive Cultures and HIV Status, Positive Cultures and Resistant IsolatesResistant Isolates

0

20

40

60

80

Positiv

e

Negat

ive

Indet

erm

inat

e

Unknown

Positive Cultures

Resistant Isolates

Num

ber

of I

sola

tes

Resistance and Decreased Resistance and Decreased Antimicrobial SusceptibilityAntimicrobial Susceptibility

020406080

100120

Penicilli

n Resis

tant

Tetra

cycline R

esista

nt

Cipro

floxa

cin R

esista

nt

Cefixi

me D

ecrea

sed S

usceptib

...

Azithro

mycin

Decr

ease

d Sus...

N=572N=572

Num

ber

of I

sola

tes

L.A. GISPL.A. GISPProject TotalProject Total

21% reported non-injection drug use21% reported non-injection drug use

7% used antibiotics7% used antibiotics

7% traveled outside CA7% traveled outside CA

1% reported injection drug use1% reported injection drug use

1% was involved in sex work1% was involved in sex work

Primary treatment for gonorrhea:Primary treatment for gonorrhea:– Ceftriaxone 250 mg (93%)Ceftriaxone 250 mg (93%)

Primary treatment for chlamydia:Primary treatment for chlamydia:– Azithromycin 1 g (98%)Azithromycin 1 g (98%)

L.A. GISPL.A. GISPTREATMENT FOR GC AND CHLTREATMENT FOR GC AND CHL

Ciprofloxacin-Resistant Ciprofloxacin-Resistant GC in CaliforniaGC in California

Prevalence of cipro-resistant GC in CA >10% in Prevalence of cipro-resistant GC in CA >10% in 20022002

CA GC Tx Recommendations:CA GC Tx Recommendations:– Avoid the use of fluoroquinolones (ciprofloxacin, Avoid the use of fluoroquinolones (ciprofloxacin,

ofloxacin, and levofloxacin) to treat GC in California.ofloxacin, and levofloxacin) to treat GC in California.– Use ceftriaxone 125mg by intramuscular (IM) injection Use ceftriaxone 125mg by intramuscular (IM) injection

to treat uncomplicated gonococcal infections of the to treat uncomplicated gonococcal infections of the cervix, urethra, and rectumcervix, urethra, and rectum

The Problem with QRNGThe Problem with QRNG

Limited availability of a recommended oral Limited availability of a recommended oral treatment regimen for gonorrhea poses treatment regimen for gonorrhea poses practical problems for treating QRNG.practical problems for treating QRNG.Besides the fluoroquinolones, cefixime, Besides the fluoroquinolones, cefixime, whose manufacture was discontinued in whose manufacture was discontinued in 2002, is the only CDC-recommended oral 2002, is the only CDC-recommended oral agent for treating gonorrhea. agent for treating gonorrhea. The health departments of California and The health departments of California and Washington state have suggested alternative Washington state have suggested alternative oral treatments (e.g., cefpodoxime 400 mg) oral treatments (e.g., cefpodoxime 400 mg) that have not yet been evaluated adequately. that have not yet been evaluated adequately.

The Challenges of MonitoringThe Challenges of MonitoringGonococcal ResistanceGonococcal Resistance

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

The Challenges of MonitoringThe Challenges of MonitoringGonococcal ResistanceGonococcal Resistance

(continued)(continued)

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

More InformationMore Information

Clinical Lab Survey Report, 2002Clinical Lab Survey Report, 2002– http://www.lapublichealth.org/std/http://www.lapublichealth.org/std/

The "Reports" section contains this and The "Reports" section contains this and other reports published by the LA County other reports published by the LA County STD Program.STD Program.

GISPGISP– http://www.cdc.gov/std/gisp/http://www.cdc.gov/std/gisp/

Resource website for information on Resource website for information on antimicrobial resistantantimicrobial resistant Neisseria Neisseria gonorrhoeaegonorrhoeae..