Sexually Transmitted Diseases

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High Percentages of Resistance to Tetracycline and Penicillin and Reduced Susceptibility to Azithromycin Characterize the Majority of Strain Types of Neisseria gonorrhoeae Isolates in Cuba, 1995–1998

SOSA, JORGE MD, PhD*; RAMIREZ-ARCOS, SANDRA PhD†; RUBEN, MARTHA MD, PhD‡; LI, HUI MSc‡; LLANES, RAFAEL MD*; LLOP, ALINA MD*; DILLON, JO-ANNE R. PhD†‡

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Abstract

Background: In many regions the susceptibility of Neisseria gonorrhoeae isolates to antimicrobial agents is rarely tested. The Gonococcal Antimicrobial Surveillance Program (GASP) in Cuba was established as part of a larger regional GASP program to facilitate the collection and reporting of antimicrobial susceptibility data for N gonorrhoeae isolates.

Goal: The goal was to retrospectively determine the antimicrobial susceptibility and molecular epidemiology of 91 isolates of N gonorrhoeae isolated from 11 centers in Cuba.

Study Design: Isolates of N gonorrhoeae were collected and presumptively identified from 11 Cuban provincial health centers. They were then forwarded to the National Laboratory of Pathogenic Neisseria Havana for confirmatory identification and were subsequently analyzed at the Center for GASP in Ottawa. Isolates were tested for susceptibility to penicillin, tetracycline, spectinomycin, ceftriaxone, ciprofloxacin, and azithromycin by the agar dilution method. To establish baseline data for molecular epidemiologic profiles, the auxotype (A), serovar (S), plasmid content (P), and TetM type of the isolates were determined. Certain A/S/P classes were further analyzed by pulsed field gel electrophoresis (PFGE).

Results: High percentages of the 91 N gonorrhoeae isolates were resistant to penicillin (68%) and tetracycline (83.5%), with 56% being penicillinase-producing (PPNG) and 64% carrying plasmid-mediated tetracycline resistance (TRNG; 50% were PP/TRNG). An additional 14% of the isolates carried chromosomal resistance (CMRNG) to either tetracycline or penicillin or both antibiotics. All isolates were susceptible to spectinomycin, ceftriaxone, and ciprofloxacin. However, nine isolates were resistant to azithromycin (MIC, ≥1.0 μg/ml), and 43 other isolates displayed reduced susceptibility to this antibiotic (MIC, 0.25–0.5 μg/ml). Although a total of 21 different A/S classes were identified, most of the isolates (61) belonged to three A/S classes: NR/IA-6 (35 isolates), NR/IB-1 (15 isolates), and P/IA-6 (11 isolates). Thirty-two of 45 PP/TRNG were A/S class NR/IA-6, and nine of the P/IA-6 isolates were TRNG. By contrast, most of A/S class NR/IB-1 (8) were CMRNG. PFGE analysis following digestion with Nhe I or Spe I further clustered the isolates into separate groups.

Conclusions: This study demonstrates high percentages of N gonorrhoeae isolates with penicillin and tetracycline resistance in Cuba. As has been noted in other studies in the Caribbean region and Latin America, resistance and reduced susceptibility to azithromycin are developing as emerging problems. Since penicillin and tetracycline continue to be widely used for the treatment of gonococcal infections in Cuba, this study indicates the importance of antimicrobial susceptibility surveillance so that effective antibiotics may be recommended for treatment of gonococcal infections.

THE ADEPTNESS OF ISOLATES of Neisseria gonorrhoeae in accruing resistance to antimicrobial agents is a formidable problem for the ongoing effective treatment and control of gonococcal disease. 1–4 In many countries, baseline data on the antimicrobial susceptibility of gonococcal isolates have not been collected. In the absence of such data, antibiotics such as penicillin or tetracycline may continue to be used despite reports from around the globe that high levels of resistance internationally preclude their use for the treatment of uncomplicated infections caused by N gonorrhoeae. Thus, the establishment of regional or national antimicrobial surveillance programs, such as the Gonococcal Antimicrobial Surveillance Program (GASP) in the Americas and the Caribbean, has become important in assisting health providers in making recommendations regarding effective antibiotics for treatment. The establishment of such baseline data is especially important when syndromic approaches are used to diagnose and treat gonococcal infections.

Antimicrobial resistance to various antibiotics is mediated in the gonococcus either through plasmid-mediated mechanisms (i.e., resistance to penicillin or tetracycline) or by mutation of various chromosomal genes (virtually all antibiotics). 1,2,4 In the Caribbean region, many countries have a high prevalence of N gonorrhoeae isolates that are resistant to penicillin. For example, in a report from Honduras, 83% of the gonococci isolated were pencillinase-producing N gonorrhoeae (PPNG), as were 78% of the isolates reported in a study from Nicaragua. 5,6 Similarly, high percentages of PPNG were noted in Jamaica (62.9%) and Guyana (73%). 7,8 High percentages of N gonorrhoeae isolates with plasmid-mediated resistance to tetracycline (TRNG) have also been reported from many Caribbean countries, with values of 74.2% in Jamaica, 87.1% in Guyana, and 51.7% in St. Vincent. 7,8

As in other parts of the world, an additional burden of resistance is presented by gonococcal isolates that carry chromosomal resistance to penicillin and tetracycline as well as to other antibiotics such as the macrolides (e.g., azithromycin) and the fluoroquinolones (e.g., ciprofloxacin). 8–11

Between 1960 and 1994, cases of gonorrhea reported in Cuba increased from 130 in 1960 to 34,224 in 1994 and 33,948 in 1997. 12 The annual incidence of gonorrhea per 100,000 population was 310.5 and 307.6 for 1994 and 1997, respectively. Although sporadic investigations of gonococcal antimicrobial susceptibility have been conducted, such studies have been limited in frequency and scope due to economic constraints. The current study was undertaken to characterize the antimicrobial susceptibility profile and molecular epidemiology (auxotype/serovar/plasmid content [A/S/P] class, TetM type, and pulsed field gel electrophoresis [PFGE] type) of 91 N gonorrhoeae isolates from 11 Cuban cities in order to establish a baseline of susceptibilities and strain types circulating between 1995 to 1998.

© Copyright 2003 American Sexually Transmitted Diseases Association

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