Laboratorio de Referencia de Neisserias, Servicio de Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain
Received 12 July 2002; returned 28 August 2002; revised 4 October 2002; accepted 10 October 2002
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Abstract |
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Keywords: gonococci, antibiotic susceptibility
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Introduction |
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Early isolates of Neisseria gonorrhoeae were extremely susceptible to antimicrobial agents; however, since the late 1950s gonococcal strains with levels of resistance against several antibiotics have been described in different countries.4 Worldwide, the more remarkable trends in antibiotic resistance are related to penicillin and quinolones. There are areas with a high proportion of tetracycline-resistant isolates, a drug frequently used in developing countries. Spectinomycin retains its activity against gonococcus, and only a few reports of resistant isolates have been described. Reduced susceptibility to third-generation cephalosporins is also rare.5
Mechanisms of antimicrobial resistance in gonococcus may be classified in two groups: the first includes the mechanisms that involve reduced access of the antibiotic to the target site through reduced permeability of the cell envelope, efflux pumps or destruction of the antibiotic before it can interact with the target; the second includes those that involve alteration of the antibiotics target.
Multiple resistance determinants may coexist in a single isolate, and resistance to multiple antibiotics is common.5
The Spanish Reference Laboratory for Neisseria (SRLN) receives unselected gonococcal strains isolated in sexually transmitted disease (STD) units across Spain sent on a voluntary basis.
In order to analyse the trends in gonococcal resistance, susceptibility testing has been carried out on all the isolates since the 1980s.
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Materials and methods |
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The ranges of concentrations were as follows: penicillin 0.007128 mg/L; cefoxitin 0.064 mg/L; ceftriaxone 0.00031 mg/L; spectinomycin 264 mg/L; tetracycline 0.0078 mg/L; and ciprofloxacin 0.001564 mg/L.
Antibiotic-containing medium was inoculated with an automatic multi-inoculator device to give a final inoculum of 104 cfu/spot. Incubation was at 37°C in a 5% CO2 atmosphere, for 2022 h. The plates were read manually, and the MICs were defined as the lowest antibiotic concentrations that inhibited bacterial growth. N. gonorrhoeae ATCC 49226 was used as a control. ß-Lactamase production was detected with a nitrocefin assay (Oxoid, Basingstoke, UK). The breakpoints used are those noted in Table 1 and obtained from the NCCLS document M100-S12.6
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Results and discussion |
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The frequency of penicillin-resistant strains increased from 14.3% in 19831984 to 56.3% in 19931994 (P < 0.01), but declined thereafter, being 16.5% in 2001. In contrast, over this last period (19942001) the percentage of strains intermediately susceptible to penicillin increased steadily from 33.3% in 19931994 to 72.2% in 19992000 (P < 0.01).
In our study, most of the strains resistant to penicillin produced ß-lactamase (88.9%). The percentage of ß-lactamase-producing resistant isolates showed important changes during the period of study, and ranged from 52.8% in 19931994 to 7.2% 4 years later (19971998) (P < 0.01).
The highest level of resistance to penicillin was detected in the ß-lactamase-producing isolates, with the majority of the ß-lactamase-producing strains (97.4%) showing MICs 4 mg/L. The situation was different among the ß-lactamase-negative resistant strains, and 66 (90.4%) showed an MIC of 2 mg/L.
Cefoxitin MIC50s and MIC90s did not change substantially during the period of study (Table 1). The percentage of intermediately susceptible strains was variable during the study, and ranged between 0.0% (19871990 and 19951996) and 16.3% in 19971998. Resistant isolates were not identified.
The emergence and spread of penicillin resistance in gonococci has determined that ceftriaxone, a broad-spectrum cephalosporin, has been recommended for the treatment of uncomplicated gonorrhoea.5,8 Resistance to ceftriaxone has not been described. A high level of susceptibility to this antibiotic was observed in our study (Table 1).
In Spain, the MIC50 of spectinomycin did not change between 1983 and 2001 (16.0 mg/L) and the MIC90 ranged from 16 to 32 mg/L. Intermediately susceptible and resistant strains were not identified.
Tetracycline resistance (MIC 2.0 mg/L) showed a decreasing trend in the first 8 years (12.0% in 19831984 versus 1.8% in 19891990; P < 0.01). After that the percentage of resistant strains rose, reaching values of up to 41.7% in 19951996 (Table 1).
It is interesting to note that over the period 19831988 N. gonorrhoeae isolates exhibiting increased resistance to tetracycline (MICs < 8.0 mg/L) were not identified. In 19891990 one strain (0.2%) had a tetracycline MIC > 8 mg/L.9 From 1990 onwards, the rate increased to 13.8% in 19951996 and then decreased to 11% in the final period of study.
The percentage of tetracycline-intermediate strains ranged from 60.7% (19911992) to 37.0% in 2001 (P < 0.01).
Ciprofloxacin intermediately susceptible strains have been isolated since the first year that we began to routinely analyse ciprofloxacin susceptibility (1993), but the first resistant strain was isolated in 2000.10 The percentage of ciprofloxacin-resistant strains increased dramatically in 2001 (Table 1).
The choice of treatment for gonococcal infections depends upon the patterns of antibiotic resistance in the geographical area being considered. This study supports that the third-generation cephalosporins, such as ceftriaxone and spectinomycin, can be used for the primary treatment of gonococcal infections in Spain. Because of the increasing prevalence of ciprofloxacin resistance detected in recent years (20002001) the treatment of gonorrhoea with fluoroquinolones should be restricted. Percentages of penicillin- and tetracycline-resistant strains were high enough to contraindicate their use for gonococcal infections in Spain.
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Acknowledgements |
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Footnotes |
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References |
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2 . Anonymous. (2001). Communicable diseases surveillance. Boletín Epidemiológico Semanal 9, 297.
3 . World Health Organization. (2001). Global Prevalence and Incidence of Selected Curable Sexually Transmitted Infections. Overview and Estimates. WHO, Geneva, Switzerland.
4 . Lind, I. (1997). Antimicrobial resistance in Neisseria gonorrhoeae. Clinical Infectious Diseases 24, Suppl. 1, 937.[ISI][Medline]
5 . Tapsall, J. (2001). Antimicrobial Resistance in Neisseria gonorrhoeae. WHO, Geneva, Switzerland.
6 . National Committee for Clinical Laboratory Standards. (2002). Performance Standards for Antimicrobial Susceptibility TestingTwelfth Informational Supplement: M100-S12. NCCLS, Wayne, PA, USA.
7 . Anonymous. (1984). Communicable diseases surveillance. Boletín Epidemiológico Semanal 1671, 402.
8 . Centers for Disease Control and Prevention. (2002). Sexually transmitted diseases treatment guidelines. Morbidity and Mortality Weekly Report 51, 178.
9 . Vázquez, J. A., Berrón, S. & Menendez, B. (1990). Isolate of TET M-containing Neisseria gonorrhoeae (TRNG) in Spain. Genitourinary Medicine 66, 3034.[ISI][Medline]
10 . Otero, L., Acalá, B., Varela, J. A., Miguel, M. D., Vázquez, J. A. & Vázquez, F. (2001). First isolate of a Neisseria gonorrhoeae strain associated with an ofloxacin treatment failure in Spain: case report. Sexually Transmitted Diseases 28, 5768.[ISI][Medline]