Sentinel Surveillance System for Antimicrobial Resistance in Clinical Isolates of Neisseria gonorrhoeae

Infections caused by strains of Neisseria gonorrhoeae that are resistant to recommended antimicrobials continue to be a growing public health problem. Over the past 3 years, the incidence of plasmid-mediated, penicillinase-producing N. gonorrhoeae (PPNG) has increased, and it now accounts for 2% of all reported gonococcal infections in the United States (1). However, the proportions of infections caused by organisms with chromosomally mediated resistance to penicillin, tetracycline, and spectinomycin and by gonococci with plasmid-mediated tetracycline resistance (TRNG) have been determined for only a limited number of localities (2,3).

The procedures for laboratory diagnosis and reporting of PPNG have been standardized, and over 90% of public health laboratories routinely test every gonococcal isolate for production of B-lactamase (CDC, unpublished data). However, ascertainment and reporting of other types of antimicrobial resistance have been inconsistent. Whereas PPNG can be detected by a rapid diagnostic test, laboratory diagnosis of chromosomally mediated resistance and TRNG requires relatively expensive antimicrobial susceptibility determination procedures on subcultures of primary isolates. Until recently, surveillance of these strains had been based on a passive reporting system; consequently, geographical areas performing more susceptibility tests than other areas may appear to have higher incidences of these strains.

Because recommendations for therapy should be based on accurate and timely surveillance of antimicrobial resistance in N. gonorrhoeae, the Division of Sexually Transmitted Diseases, Center for Prevention Services, CDC, in cooperation with the Sexually Transmitted Diseases Laboratory Program, Center for Infectious Diseases, CDC, and state and local health departments, has organized the Gonococcal Isolate Surveillance Project (GISP).

In this project, each of four regionally based laboratories chosen for their expertise in performing antimicrobial susceptibility determinations processes a prospective consecutive sample of isolates from five sexually transmitted disease clinics. Each month, the first 25 urethral isolates from male patients in each clinic are submitted to the regional laboratories where a test for B-lactamase is performed and minimum inhibitory concentrations (MICs) to penicillin, tetracycline, spectinomycin, cefoxitin, and ceftriaxone are determined. Classification of the isolates is based on the CDC surveillance definitions of plasmid-mediated resistance (PPNG, TRNG) and chromosomally mediated resistance (4). This report summarizes the results from the first 15 participating clinics.

Between August 1986 and July 1987, 1,420 gonococcal isolates were evaluated. Nineteen isolates (1%) were PPNG, and 64 (5%) were TRNG (Table 1). Forty-five of the TRNG isolates were reported from Baltimore, where TRNG accounted for 15% (45/300) of gonococcal isolates. For the 1,337 non-PPNG, non-TRNG isolates, the geometric mean MIC to penicillin was 0.19 ug/ml; to tetracycline, it was 0.66 ug/ml; to cefoxitin, 0.33 ug/ml; to spectinomycin, 16.5 ug/ml; and to ceftriaxone, 0.003 ug/ml. Thirteen percent of the isolates without plasmid-mediated resistance were chromosomally resistant to penicillin, and 48% of them were chromosomally resistant to tetracycline (Figure 1). No isolates were resistant to spectinomycin or ceftriaxone. Reported by: Gonococcal Isolate Surveillance Project participants. Regional Laboratories. Sexually Transmitted Diseases Laboratory Program, Center for Infectious Diseases; Div of Sexually Transmitted Diseases, Center for Prevention Svcs, CDC.

Editorial Note

Editorial Note: This is the first nationally based prospective survey of antimicrobial resistance in N. gonorrhoeae in the United States since the National Gonorrhea Therapy Monitoring Study (NGTMS) was conducted from 1972 to 1977 (5,6). Previous nationally based reports of chromosomally mediated resistance and TRNG have been limited to summaries of outbreaks and the passive reporting of sporadically occurring cases (7,8).

The preliminary GISP survey data underestimate the proportion of infections caused by PPNG strains because New York and Florida, which accounted for 58% of PPNG reported in 1986 (1), are not represented in the initial GISP survey results. The distribution of TRNG reflects a high prevalence of disease in Baltimore, as previously reported (9). Excluding the Baltimore cases, TRNG represents 2% (19/1,120) of the national sample.

The high incidence of gonococci with chromosomally mediated resistance to penicillin and tetracycline confirms published reports of geographically limited studies in Seattle and Vancouver (2,3). Although no organisms in our sample were resistant to ceftriaxone, 27 (2%) of the isolates had MICs of 0.06-0.25 ug/ml and met the criteria for intermediate susceptibility. Trends in ceftriaxone susceptibility will require continued monitoring as this and other third-generation cephalosporins are used more frequently in the treatment of gonorrhea. These results, when compared with those from the NGTMS, show a marked decrease in susceptibility to penicillin and tetracycline. Limited GISP trend data suggest that the incidence of chromosomally mediated resistant organisms will continue to increase.

In localities where the proportion of gonococcal strains meeting CDC surveillance definitions of antimicrobial resistance is greater than or equal to1% for 2 consecutive months, treatment and disease-intervention protocols may require modification. Management and treatment guidelines for infections caused by antimicrobial-resistant N. gonorrhoeae are being published as an MMWR supplement and will be available later this month. References

1. CDC. Penicillinase-producing Neisseria gonorrhoeae--United States, 1986. MMWR 1987; 36:107-8.

2. Bowie WR, Shaw CE, Chan DGW, Jones HD, Black WA. In-vitro susceptibility of 400 isolates of Neisseria gonorrhoeae in Vancouver, 1982-84. Can Med Assoc J 1986;135:489-93.

3. Hook EW, Knapp JS, Handsfield HH, et al. Characterization and prevalence of chromosomally mediated resistance to penicillin G and tetracycline in Neisseria gonorrhoeae from Seattle, Washington. In: Schoolnik GK, ed. The pathogenic Neisseriae: proceedings of the fourth international symposium, Asilomar, California, 21-25 October 1984. Washington, DC: American Society for Microbiology, 1985:96-100.

4. CDC. Antibiotic-resistant strains of Neisseria gonorrhoeae: policy guidelines for detection, management, and control. MMWR 1987;36(5S)(end-ind):(In press).

5. Jaffe HW, Biddle JW, Thornsberry C, et al. National gonorrhea therapy monitoring study: in-vitro antibiotic susceptibility and correlation with treatment results. N Engl J Med 1976; 294:5-9.

6. Reynolds GH, Zaidi AA, Thornsberry C, et al. The national gonorrhea therapy monitoring study: II. trends and seasonality of antibiotic resistance of Neisseria gonorrhoeae. Sex Transm Dis 1979;6:103-11.

7. Rice RJ, Biddle JW, JeanLouis YA, DeWitt WE, Blount JH, Morse SA. Chromosomally mediated resistance in Neisseria gonorrhoeae in the United States: results of surveillance and reporting, 1983-1984. J Infect Dis 1986;153:340-5.

8. Knapp JS, Zenilman JM, Biddle JW, et al. Frequency and distribution in the United States of strains of Neisseria gonorrhoeae with plasmid-mediated, high-level resistance to tetracycline. J Infect Dis 1987;155:819-22.

9. Brewer F, Matuszak DL, Libonati JP, Jackman NER, Israel E. Tetracycline-resistant Neisseria (Letter). New Engl J Med 1986;315:1548-9.

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