Epidemiologic Notes and Reports Penicillin-Resistant Gonorrhea -- North Carolina

Between February 14 and May 15, 1983, 56 cases of penicillin-resistant gonococcal infection, occurring in 55 persons, were reported in Durham County, North Carolina (Figure 1). These cases represent the first reported outbreak of gonorrhea caused by strains that are resistant to penicillin but that do not produce penicillinase. Thirty (55%) of the 55 affected patients were men. Ages ranged from 15 to 50 years (median 24 years). All patients were reported to be heterosexual.

The first case involved a 31-year-old man who reported to the local health department on February 14 with a 1-day history of urethral discharge. Intracellular, gram-negative diplococci were demonstrated in a urethral smear. The patient was initially treated with 4.8 million units of aqueous procaine penicillin G (APPG) but returned on February 23 because of persistent urethral discharge. He was re-treated with 4.8 million units of APPG along with 1 g probenecid. A urethral culture subsequently grew Neisseria gonorrhoeae resistant to penicillin by disc susceptibility testing and negative for penicillinase by the rapid paper-strip method. On March 8, the patient was treated with spectinomycin 2 g intramuscularly (IM).

The second recognized case involved a 22-year-old prostitute; she was a partner of a patient with gonorrhea. She was first treated on February 17 with 4.8 million units APPG. She returned on February 23 as an asymptomatic contact of the same patient with presumtive non-gonococcal urethritis (NGU) and was given a 7-day course of tetracycline. Her pretreatment cultures at both visits grew N. gonorrhoeae resistant to penicillin but non-penicillinase producing. This patient, her asymptomatic male partner, and his female partner (a prostitute) were treated on February 28 with spectinomycin 2 g IM. Cultures from the latter two persons (the third and fourth cases) also grew non-penicillinase-producing gonococci resistant to penicillin. Interviewers determined the female prostitute (the fourth case) had also had sexual contact on February 10 with the first patient who had presented on February 14.

Sporadic cases continued to occur through April, with three or more cases being reported each week. Intensive screening measures implemented on May 2 led to increased recognition and reporting of cases. All gonococcal isolates from Durham County were tested for penicillin susceptibility using both the disc diffusion test and gonococcal agar base containing 1 ug/ml penicillin. Hospital and commercial laboratories in Durham County were notified of the outbreak and encouraged to perform similar laboratory tests for gonococcal isolates.

Isolates from all 55 patients were studied and confirmed as penicillin-resistant and non-penicillinase-producing at the Department of Microbiology and Immunology, University of North Carolina--Chapel Hill. Thirty-six of these isolates were further studied. All 36 were prototrophic auxotypes. They were highly resistant to penicillin (minimal inhibitory concentration (MIC) 2-4 ug/ml) and moderately resistant to erythromycin (MIC 2-4 ug/ml) and tetracycline (MIC 2-4 ug/ml), but all were susceptible to spectinomycin. The principal outer membrane protein I (POMPI) was identical in all 20 isolates tested.

Control measures have included obtaining specimens for culture and then treating all men whose urethral smears show gram-negative intracellular diplococci with spectinomycin 2 g IM; sexual partners are treated similarly. Efforts will be made in Durham County to promptly refer and treat sexual partners of patients, obtain specimens for gonorrhea cultures from prostitutes approximately every week, and promptly identify and treat those from whom gonococci are cultured. Reported by JD Fletcher, MD, JD Stratton, MD, CS Chandler, Durham County Health Dept, PF Sparling, MD, Dept of Microbiology and Immunology, University of North Carolina School of Medicine--Chapel Hill, Venereal Disease Control Br, North Carolina Div of Health Svcs, MP Hines, DVM, State Epidemiologist, North Carolina State Dept of Human Resources; Div of Venereal Disease Control, Center for Prevention Svcs, Div of Field Svcs, Epidemiology Program Office, CDC.

Editorial Note

Editorial Note: Non-penicillinase-producing strains of N. gonorrhoeae that are highly resistant to penicillin are apparently uncommon in the United States. Among 11,103 isolates tested at CDC between 1972 and 1979, 38 (0.3%) had MICs to penicillin of 2 ug/ml or greater (1). This outbreak, therefore, represents an unusual event due to transmission of a single resistant strain, as demonstrated by the antibiotic resistance pattern, auxotyping data, and outer membrane protein studies. Such transmission of a single strain of gonococcus once introduced into a community has previously been described (2).

The importance of this type of penicillin resistance is still undetermined. Treatment failures increase as the MICs of gonococci increase (3). Several tests can be used to detect penicillinase-producing gonococci (PPNG); however, procedures to identify non-PPNG penicillin-resistant strains have yet to be standardized and adopted for routine laboratory use. Reports of these strains may rapidly increase as screening procedures are employed. In Southeast Asia, more than 20% of gonococcal isolates are non-PPNG strains resistant to penicillin. Some countries have already identified these strains (4), and it is possible that similar strains are already widely distributed but unrecognized in the United States.

Non-PPNG penicillin-resistant strains should be suspected when increases in treatment failures not due to PPNG are noted. Screening for these strains may be accomplished by disc diffusion tests (10 ug penicillin disc) on post-treatment isolates. Isolates with a zone size less than 25 mm can be considered resistant to penicillin and should be forwarded to a reference laboratory for confirmation by MIC studies. When necessary, CDC can perform these MIC studies. To avoid continued transmission of these resistant strains, control measures similar to those for PPNG outbreaks should be employed (5).

References

1. CDC. Unpublished data.

2. Handsfield HH, Sandstrom EG, Knapp JS, et al. Epidemiology of penicillinase-producing Neisseria gonorrhoeae infections: analysis by auxotyping and serogrouping. N Engl J Med 1982;306:950-4.

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

4. Brown S, Biddle J, Warnnisorn T, Panikabutra K, Traisupa A. Antimicrobial resistance of Neisseria gonorrhoeae in Bangkok: is single-drug treatment passe. Lancet 1982;2:1366-8.

5. CDC. Penicillinase-producing Neisseria gonorrhoeae--Los Angeles. MMWR 1983;32:181-3.

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