Tetracycline-Resistant Neisseria gonorrhoeae -- Georgia, Pennsylvania, New Hampshire

Since February 1985, CDC has identified 12 isolates of Neisseria gonorrhoeae that have high-level resistance to tetracycline (minimal inhibition concentration (MIC) 24-32 ug/ml) but are susceptible to penicillin. This high level of tetracycline resistance appears to be a new phenomenon.

Nine of the cases were reported from the metropolitan Atlanta, Georgia, area, and three, from Philadelphia, Pennsylvania. Ten of the patients were males: two were homosexual; six were heterosexual; and in two cases, sexual preference was not known. Two patients were heterosexual women. Positive cultures were obtained from urogenital sites. Six patients were initially treated with oral tetracycline alone. Five of these were reevaluated after therapy, and all were clinical treatment failures with positive test-of-cure cultures. Eight of the patients from whom information was available denied antibiotic use in the 2 weeks preceding their initial clinic visit.

Review of Sexually Transmitted Diseases Laboratory Program records at CDC over the previous 2 years identified one additional tetracycline-resistant N. gonorrhoeae (TRNG) case, reported from New Hampshire in 1983. This was a 28-year-old homosexual male who had positive posttreatment cultures from both the rectum and pharynx after initial treatment with tetracycline for gonococcal infection at those sites.

The identification of N. gonorrhoeae was confirmed by standard biochemical and immunologic methods. None of these strains produced B-lactamase. Isolates were tested at CDC by the agar dilution method for sensitivity to penicillin, ampicillin, tetracycline, minocycline, doxycycline, cefotaxime, cefuroxime, cefoxitin, spectinomycin, and trimethoprim/sulfamethoxazole. All were resistant to tetracycline (MIC 16-32 ug/ml), doxycycline (MIC 8-24 ug/ml), and minocycline (MIC 12-32 ug/ml). The isolates were uniformly susceptible to penicillin (MIC 0.008-0.25 ug/ml) and the other antibiotics tested. All the isolates were proline auxotrophs and belonged to serogroup IB with three distinct serovariants represented. Of the 13 isolates tested, all contained plasmids of approximately 24.5 and 2.6 megadaltons. Genetic analysis indicated that deoxyribonucleic acid (DNA) from these strains did not hybridize to a known enteric tetracycline resistance determinant, nor were these strains able to function as genetic donors of tetracycline resistance to sensitive strains of N. gonorrhoeae either by conjugation or by DNA-mediated transformation.

A prospective surveillance study was conducted in Dekalb County, Georgia. From August 15, to September 6, 1985, all N. gonorrhoeae isolates recovered by the Dekalb County Health Department were tested by CDC for their ability to grow on supplemented chocolate agar containing 2.5 ug of tetracycline per ml. Isolates obtained through this screening procedure were further tested for antimicrobial susceptibility as above. Of 174 confirmed gonococcal isolates, six (3.4%) were found to have high-level resistance to tetracycline. Between January 1983 and December 1984, CDC determined MIC to tetracycline on over 9,500 gonococcal isolates, and with the exception of the New Hampshire case cited here, no TRNG were identified. Reported by R Carson, Matthew Thornton Health Plan, Nashua, New Hampshire, E Tasker, B Houle, G Bardsley, J Hedderick, Div of Public Health Svcs, New Hampshire Dept of Health and Welfare; M Goldberg, R Sharrar, MD, Div of Disease Control, Philadelphia Dept of Public Health; R Miller, R Poole, Dekalb County Health Dept; Georgia State Laboratory, Div of Sexually Transmitted Diseases, Center for Prevention Svcs, Sexually Transmitted Diseases Laboratory Program, Center for Infectious Diseases, CDC.

Editorial Note

Editorial Note: This is the first report of multiple isolates of N. gonorrhoeae resistant to tetracycline at this high level. Tetracycline resistance has usually been associated with penicillinase-producing strains (PPNG) (1) and with chromosomally resistant N. gonorrhoeae (CMRNG) (2,3). Strains exhibiting moderate levels of tetracycline resistance (MIC 1-8 ug/ml) have been noted previously. This type of resistance is thought to result from additive effects of mutations at three independent genetic loci (4,5). However, the inability of the TRNG strains cited in this report to function as donors of tetracycline resistance strongly suggests that this is a new type of resistance and does not result from previously described genetic determinants. Although all TRNG isolates to date have been sensitive to penicillin, preliminary data indicate that they may have the capability to acquire and maintain a B-lactamase plasmid.

The magnitude of the tetracycline MICs reported here, and their association with treatment failures, raises public health concerns, since tetracycline (minocycline, doxycycline) is sometimes used as the sole therapy for gonococcal genital infections and as neonatal prophylaxis for ophthalmia neonatorum.

In light of this new development, CDC strongly urges that all positive test-of-cure cultures be screened for tetracycline resistance by disk diffusion in addition to recommended procedures for PPNG and CMRNG testing (3,6). All gonococcal isolates with an inhibitory zone of less than 30 mm to a 30 ug tetracycline disc on supplemented chocolate agar should be submitted to a reference laboratory for confirmation by agar dilution techniques. The 1985 CDC Sexually Transmitted Diseases Treatment Guidelines (7) will emphasize that tetracycline (minocycline, doxycycline) therapy alone should be used only in patients with reported penicillin allergy. These patients should be strongly encouraged to return for a posttreatment evaluation.

References

1. 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.

2. Faruki A, Kohmescher RN, McKinney P, Sparling PF. A community-based outbreak of infection with penicillin resistant Neisseria gonorrhoeae not producing penicillinase (chromosomally mediated resistance). N Engl J Med 1985;313:607-11.

3. Rice RJ, Blount JH, Biddle JW, JeanLouis Y, Morse SA. Changing trends in gonococcal antibiotic resistance in the United States 1983-1984. CDC surveillance summaries 1985;33:11SS-5SS.

4. Sarubbi FA Jr, Blackman E, Sparling PF. Genetic mapping of linked antibiotic resistance loci in Neisseria gonorrhoeae. J Bacteriol 1974;120:1284-92.

5. Sparling PF, Sarubbi FA Jr, Blackman E. Inheritance of low-level resistance to penicillin, tetracycline, and chloramphenicol in Neisseria gonorrhoeae. J Bacteriol 1975;124:740-9.

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

7. CDC. Sexually transmitted disease treatment guidelines--1985. MMWR 1985 (in press).

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