Epidemiologic Notes and Reports Chromosomally Mediated Resistant Neisseria gonorrhoeae -- United States

During 1983-1984, an increasing number of cases of B-lactamase negative, penicillin-resistant Neisseria gonorrhoeae were reported to CDC. Unlike penicillinase-producing N. gonorrhoeae (PPNG), which have plasmid-mediated resistance to penicillin, these B-lactamase negative, resistant gonococci have chromosomally mediated resistance based on available data.

The first reported outbreak of chromosomally mediated (B-lactamase negative) resistant N. gonorrhoeae (CMRNG) in the United States occurred in Durham County, North Carolina (1). Since this outbreak, in which more than 200 cases were eventually detected, 16 other states have reported cases with resistant gonococci. Of these, Tennessee, New Mexico, and Oregon have reported more sustained outbreaks.

Cases in these outbreaks were detected either by routine screening of all gonococcal isolates (New Mexico) or screening of primary treatment failure isolates (Tennessee, Oregon) for susceptibility to penicillin at the local or state levels. Screening was performed by disk agar diffusion or by growth on penicillin-containing media. Gonococcal isolates that grew on media containing 1.6 ug/ml of penicillin or produced a zone of inhibition less than 26 mm, with a 10-Unit penicillin disk, were submitted to CDC for confirmation of resistance. Minimum inhibitory concentrations by the agar dilution susceptibility test were determined for antimicrobials that included penicillin, ampicillin, tetracycline, cefotaxime, cefuroxime, cefoxitin, spectinomycin, and trimethoprim/sulfamethoxazole. Isolates resistant to penicillin and ampicillin were equally resistant to tetracycline by agar dilution susceptibility testing.

Of all CMRNG isolates submitted to CDC for agar dilution susceptibility testing during 1983-1984, 11.0% were susceptible to less than 2 ug/ml of penicillin; none were susceptible to less than 2 ug/ml of tetracycline; and only 47.0% were susceptible to less than 0.5 ug/ml trimethoprim and 9.5 ug/ml sulfamethoxazole (trimethoprim/sulfamethoxazole). All isolates were susceptible to spectinomycin, cefoxitin, cefuroxime, and cefotaxime. Immunologic characterization demonstrated that all CMRNG isolates were serogroup IIb (the majority of the same serovariant) based on serotyping by experimental monoclonal antibodies to major outer membrane protein (2). Of the 18 New Mexico cases, two distinctly different serovariants were detected within serogroup IIb.

Clinical and epidemiologic information were obtained for patients whose isolates were tested. Excluding North Carolina, of the 16 other reporting states, over half of the CMRNG cases were from Tennessee, New Mexico, and Oregon.

Tennessee: All the 14 Tennessee patients were heterosexuals, and two patients could be linked to interstate travel to Virginia or North Carolina. Strains from the Tennessee cases were immunologically similar and had similar antimicrobial susceptibility patterns consistent with continued endemic transmission within the state.

New Mexico: Of the 18 CMRNG patients from New Mexico, seven were heterosexual (three males, four females), and 11 were homosexual males. All heterosexual patients and seven homosexual patients were infected with gonococcal strains immunologically identical, with similar antimicrobial susceptibility patterns. Strains from these cases were more resistant to penicillin than strains from the other four homosexual patients. Heterosexual CMRNG patients could not be linked to homosexual CMRNG patients by sexual history or naming of sexual contacts. All homosexual patients were clustered within Albuquerque; heterosexual patients were more widely distributed throughout the state. Based on immunologic studies of the gonoccoci recovered from these individuals and examination of temporal and geographic variables for heterosexuals versus homosexuals, at least two separate outbreaks with no demonstrable common source occurred in New Mexico. No evidence for interstate or foreign transmission into New Mexico could be identified for any of the cases.

Oregon: Of the eight cases reported from Oregon, all occurred among homosexual males. Gonococcal strains from these individuals shared identical immunologic and antimicrobial susceptibility patterns. No epidemiologic evidence for interstate or foreign transmission could be documented for any of these cases, suggesting only endemic transmission within the homosexual community in Oregon. No additional cases have been reported from Oregon since March 1984. Reported by M Kimberly, DrPh, State Laboratory Director, W DeVault, CE Chapman, MD, G Conrad, Venereal Disease Control, RH Hutcheson, Jr, MD, State Epidemiologist, Tennessee State Dept of Health; JM Mann, MD, L Nims, Scientific Laboratory, A Chowning, E Montes, Venereal Disease Control, HF Hull, MD, State Epidemiologist, Health Svcs Div, New Mexico Dept of Health and Environment, L Foster, MD, D Harger, H Horton, Venereal Disease Control, C Schade, MD, JA Googins, MD, State Epidemiologist, State Health Div, Oregon Dept of Human Resources; Sexually Transmitted Diseases Laboratory Program, Center for Infectious Diseases, Div of Sexually Transmitted Diseases, Center for Prevention Svcs, Div of Field Svcs, Epidemiology Program Office, CDC.

Editorial Note

Editorial Note: Seventeen states, including North Carolina, have reported cases of CMRNG to CDC since 1983. The majority of these cases were detected as primary therapeutic failures to the penicillins or tetracyclines. Gonococcal strains from the majority of U.S. outbreaks and cases have generally been immunologically similar (serogroup IIb) with similar antimicrobial susceptibilities.

Based on epidemiologic data, foreign importation has been infrequently documented for these CMRNG strains in the United States (3). In contrast, foreign importation contributes to the largest proportion of PPNG in the United States, although domestic transmission became more important after 1976 (4).

Cases of CMRNG may be detected by screening for penicillin resistance at the local or state levels to guide appropriate therapy and permit rapid follow-up of cases. Screening by disk agar diffusion or with penicillin-containing media will identify chromosomally mediated resistance to penicillin. Disk susceptibility testing to tetracycline and trimethoprim/sulfamethoxazole should be performed only by standardized procedures using appropriate controls (5,6). Inconsistent results to these two antimicrobials may be seen with disk susceptibility testing (5,6).

Based on agar dilution susceptibility testing, infections caused by CMRNG should clinically respond to therapy with recommended dosages of spectinomycin, cefoxitin, cefotaxime, or cefuroxime. CDC treatment guidelines for PPNG infections provide the recommended schedules for these antimicrobials and emphasize the importance of the immediate use of spectinomycin as primary therapy for gonorrhea cases when treatment failures are suspected (7).

Since 1975, gonorrhea has generally declined in the United States (8). PPNG increased dramatically between 1976 and 1982 but decreased in 1983 (8). Unfortunately, cases of CMRNG have been reported with increasing frequency since the North Carolina outbreak. Because the extent and prevalence of CMRNG infections are not yet fully understood, screening of all B-lactamase negative (nonpenicillinase-producing) primary treatment failure gonococcal isolates for penicillin susceptibility (1) is encouraged at the local and state levels to improve surveillance and guide appropriate therapy. Screening at the community level should be most cost-effective, since the majority of these CMRNG strains are equally resistant to tetracycline, thereby preventing unnecessary and usually ineffective retreatment with a tetracycline. Because of high secondary treatment failure rates with tetracycline, tetracycline should not be used as the drug of choice for either PPNG or CMRNG infections that have failed primary therapy with penicillin or ampicillin. Spectinomycin, cefoxitin, or cefotaxime should be used to treat CMRNG infections at dosages recommended for PPNG (7).

More active surveillance for these CMRNG infections will be required to determine their accurate prevalence, and support control activities.

References

1. CDC. Penicillin-resistant gonorrhea--North Carolina. MMWR 1983;32:273-5.

2. Tam MR, Buchanan TM, Sandstrom EG, Holmes KK, et al. Serological classification of Neisseria gonorrhoeae with monoclonal antibodies. Infect and Immun 1982;36:1042-53.

3. CDC. Gonorrhea surveillance reports, 1975-1984.

4. Jaffe HW, Biddle JW, Johnson SR, Wiesner PJ. Infections due to penicillinase producing Neisseria gonorrhoeae in the United States: 1976-1980. J Infect Dis 1981;144:191-7.

5. Biddle JW, Swenson JM, Thornsberry C. Disc agar diffusion antimicrobial susceptibility tests with beta-lactamase producing Neisseria gonorrhoeae. J Antibiot 1978;31:352-8.

6. Barry AL. "Diffusion test procedures." The antimicrobic susceptibility test: principles and practices. Philadelphia, Pennsylvania: Lea & Sebiger 1976:180-207.

7. CDC. Sexually transmitted diseases treatment guidelines, 1982. MMWR Supplement, 1982;31:35S-62S.

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