Plasmid-Mediated Antimicrobial Resistance in Neisseria gonorrhoeae -- United States, 1988 and 1989

Because the prevalence of antimicrobial resistance in Neisseria gonorrhoeae increased during the early 1980s (1), in 1986 CDC implemented the Gonococcal Isolate Surveillance Project (GISP) to monitor antimicrobial susceptibilities at 21 collaborating sexually transmitted disease clinics in 21 cities (Figure 1) (2). Each month, isolates from the first 20 men* with urethral gonococcal infections at each clinic are submitted to one of four regional laboratories for susceptibility testing. This report describes the results of surveillance for plasmid-mediated resistance in N. gonorrhoeae in 1988 and 1989.

During these 2 years, 9309 gonococcal isolates (4620 in 1988 and 4689 in 1989) were collected from the 21 clinics. Strains were isolated primarily from black (76.6%), heterosexual (95.9%) men; the median age of the men was 25 years.

The susceptibilities (minimum inhibitory concentrations (MICs)) to penicillin, tetracycline, spectinomycin, and ceftriaxone were determined for each isolate. The definitions of susceptibility to these antimicrobial agents are those of the National Committee for Clinical Laboratory Standards and CDC (3). Penicillinase-producing N. gonorrhoeae (PPNG) was identified with a beta-lactamase test. An MIC of greater than or equal to 16.0 ug tetracycline/mL identified presumptively an isolate as having plasmid-mediated, high-level resistance to tetracycline (tetracycline-resistant N. gonorrhoeae (TRNG)). Isolates that produced beta-lactamase and had an MIC of greater than or equal to 16.0 ug tetracycline/mL were classified as PPNG/TRNG. Plasmid-mediated resistance to ceftriaxone or spectinomycin has not been observed in N. gonorrhoeae.

PPNG. In 1988, PPNG accounted for 149 (3.2%) isolates (range: 0.0%-10.4%; median: 3.0%), and in 1989, 346 (7.4%) isolates (range: 1.2%-31.7%; median: 5.0%) (Table 1). From 1988 to 1989, statistically significant increases (p less than 0.05) in the percentage of PPNG occurred in seven clinics (Atlanta, Birmingham, Boston, Long Beach, Philadelphia, San Antonio, and San Diego). PPNG rates remained approximately the same in the other 14 clinics.

TRNG. In 1988, TRNG accounted for 184 (4.0%) isolates (range: 0.0%-32.0%; median: 0.8%), and in 1989, 229 (4.9%) isolates (range: 0.0%-19.8%; median: 1.7%). In both years, the percentage of infections with TRNG was highest among clinics in the east and southeast (Table 2). From 1988 to 1989, statistically significant increases (p less than 0.05) in the percentage of TRNG were observed in four clinics (Birmingham, Denver, St. Louis, and West Palm Beach); significantly fewer (p less than 0.05) TRNG were isolated from patients in Atlanta and Baltimore.

PPNG/TRNG. PPNG/TRNG accounted for 15 (0.3%) and 41 (0.9%) isolates in 1988 and 1989, respectively. PPNG/TRNG strains were isolated most frequently from patients in Philadelphia, where they accounted for 4.2% of all isolates in 1988 and 9.7% of all isolates in 1989. PPNG/TRNG strains were isolated from one patient at each of five other clinics in 1988 (Albuquerque; Boston; Fayetteville, North Carolina; San Antonio; and San Francisco) and from 18 patients at six other clinics in 1989 (Baltimore, Boston, Denver, Fayetteville, San Antonio, and San Francisco). Reported by: HH Handsfield, MD, J Schwebke, MD, Seattle-King County Dept of Public Health, Seattle, Washington. EW Hook, III, MD, Baltimore City Health Dept and Johns Hopkins Univ, Baltimore, Maryland. FN Judson, MD, Denver Health and Hospitals, Denver, Colorado. SE Thompson, MD, Emory Univ School of Medicine, Atlanta. Div of Sexually Transmitted Diseases Laboratory Research, Center for Infectious Diseases; Div of STD/HIV Prevention, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: Although national gonorrhea rates changed little from 1988 (302 per 100,000 persons) to 1989 (298 per 100,000), important increases occurred in the percentage of isolates with plasmid-mediated resistance. PPNG was first isolated in the United States in 1976. From 1976 through 1981, the prevalence of PPNG infections increased slowly; foci of infections were identified in Los Angeles, Miami, and New York City. From 1981 through 1986, the prevalence of PPNG infections increased more than fivefold (1). This increasing prevalence prompted the recommendation that penicillins be virtually abandoned as single-dose, primary therapy for gonorrhea (4).

From 1988 through 1989, PPNG was isolated at all clinics participating in GISP; in 15 of the clinics in 1989, the percentage of PPNG infections exceeded the definition for "hyperendemicity" of PPNG (prevalence greater than or equal to 3.0%) (4). Although clinics in Los Angeles, Miami, and New York City are not participating in GISP, the percentage of PPNG infections remains high in those cities (CDC, unpublished data). The percentage of PPNG infections in the clinics participating in GISP indicates that PPNG has spread beyond its initial geographic foci and now represents a public health problem in all regions of the United States.

TRNG was first described in 1986 (5). Infections with TRNG appear to be most common in the eastern United States; in 1989, however, of the four clinics reporting substantial increases in the percentage of TRNG, one was in the midwest (St. Louis), and one in the west (Denver). These data suggest that further spread of TRNG from eastern to western cities is likely. In 1985, based on previously describedresistance caused by chromosomal mutations, CDC recommended that tetracycline not be used as sole therapy for gonorrhea (6); the subsequent emergence of TRNG has further emphasized the importance of this recommendation.

TRNG is important for two reasons: first, because it has high-level resistance to tetracycline, and second, because experimentally its 25.2-megadalton (Mdal) TetM-containing plasmids may transfer both itself and beta-lactamase plasmids to Neisseria and related species (7). This conjugative ability of the 25.2-Mdal plasmid may have resulted in the emergence of PPNG/TRNG (7). PPNG/TRNG accounted for a small proportion of all isolates examined in 1988 and 1989. However, because these isolates accounted for 9.7% of all N. gonorrhoeae isolates from the Philadelphia clinic in 1989, and because the frequency of PPNG/TRNG isolates identified from other clinics increased almost threefold between 1988 and 1989, infections caused by these strains will further challenge the selection of gonorrhea therapies.

Despite the increase in the frequency of strains with plasmid-mediated resistance to penicillins and tetracycline, all isolates examined were susceptible to ceftriaxone (MIC less than or equal to 0.25 ug/mL), and fewer than 1% were resistant to spectinomycin (MIC greater than or equal to 128 ug/mL) (CDC, unpublished data). Initial therapy for gonococcal infection with ceftriaxone (250 mg intramuscularly), or an antimicrobial agent with proven equivalency, remains an integral component of the strategy for gonorrhea control (8).

References

1. Whittington WL, Knapp JS. Trends in antimicrobial resistance in Neisseria gonorrhoeae in the United States. Sex Transm Dis 1988;15:202-10.

2. CDC. Sentinel surveillance system for antimicrobial resistance in clinical isolates of Neisseria gonorrhoeae. MMWR 1987;36:585-6,591-3.

3. CDC. Disk diffusion antimicrobial susceptibility testing of Neisseria gonorrhoeae. MMWR 1990;39:167-9.

4. CDC. Policy guidelines for the detection, management, and control of antibiotic-resistant strains of Neisseria gonorrhoeae. MMWR 1987;36(no. 5S).

5. Morse SA, Johnson SR, Biddle JW, Roberts MC. High-level tetracycline resistance in Neisseria gonorrhoeae is due to the acquisition of the streptococcal tetM determinant. Antimicrob Agents Chemother 1986;30:664-70.

6. CDC. 1985 STD treatment guidelines. MMWR 1985;34(no. 4S).

7. Roberts MC, Knapp JS. Host range of the conjugative 25.2-Mdal tetracycline resistance plasmid from Neisseria gonorrhoeae and related species. Antimicrob Agents Chemother 1988;32:488-91.

8. CDC. 1989 Sexually transmitted diseases treatment guidelines. MMWR 1989;38(no. S-8). *Isolates were collected from the first 25 men; isolates 21-25 were used to replace missing isolates in the sequence 1-20.

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