1 Laboratorio de Referencia de Neisserias, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Majadahonda, Madrid; 2 Hospital Monte Naranco, Facultad de Medicina, Oviedo; 3 Servicio de Microbiología, Hospital de Cabueñes, Gijón, Spain
Sir,
Gonorrhoea and chlamydial infections are the most frequent sexually transmitted diseases globally. Over the past few years, several studies have been carried out to define the efficacy of azithromycin, a modified macrolide antibiotic, for treatment of both of these sexually transmitted diseases. These studies have shown that a single oral dose of azithromycin would ensure adequate therapy for both infections.1
Because Neisseria gonorrhoeae quickly develop resistance to antimicrobial agents,2 it is necessary to have information on azithromycin susceptibility. Gonococcal strains showing decreased susceptibility to azithromycin have been described in several countries.3,4
The susceptibility of gonococcal strains to ß-lactams (penicillin, cefoxitin and ceftriaxone), tetracycline, spectinomycin and fluoroquinolones (ciprofloxacin) is routinely tested in the Spanish Neisseria Reference Laboratory. Azithromycin susceptibility has not been studied.
Sixty-three gonococcal isolates were tested. These strains were isolated in several Spanish towns from 1992 to 2001. Fifty were IB serotype and the other 13 were IA.
Susceptibility to azithromycin was determined by the agar dilution method in supplemented GC agar, using the range 0.01516 mg/L. Antibiotic-containing medium was inoculated with an automatic multi-inoculator that dispensed a final inoculum of 104 cfu/spot. Incubation was at 37°C in 5% CO2 for 2022 h. The plates were read manually and the MICs were defined as the lowest concentration that inhibited bacterial growth. Staphylococcus aureus ATCC 29213 was used as a control.
Interpretative criteria for the results of azithromycin susceptibility tests have not been established by NCCLS. However, several studies suggest that values of 0.251 mg/L describe decreased susceptibility and 2 mg/L indicates resistance for strains incubated in 5% CO2.3
In our study, MIC50 and MIC90 were 0.25 and 0.5 mg/L, respectively (Table 1). The percentage of strains showing decreased susceptibility to azithromycin was very high (58%), and two strains were defined as resistant (MIC = 4 mg/L). A similar situation has been described in other countries where azithromycin is used for the treatment of uncomplicated gonococcal infections.3,4
Several studies have demonstrated that decreased susceptibility to azithromycin in N. gonorrhoeae is mainly due to an overproduction of the mtr(CDE)-encoded efflux pump determined by mtrR mutations.5,6
In order to determine whether the level of susceptibility changed along the years of study, we analysed the results over two periods: 19921999 and 20002001. MIC50 and MIC90 were the same (Table 1). There was no significant difference in the percentage of strains with intermediate susceptibility to azithromycin between both periods.
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The finding of resistant isolates underscores the importance of azithromycin susceptibility surveillance for defining the proper use of this antibiotic for the treatment of gonococcal infections in Spain.
Footnotes
* Corresponding author. Tel: +34-1-509-7901; Fax: +34-1-509-7966; E-mail: jvazquez{at}isciii.es
References
1 . Robinson, A. J. & Ridgway, G. L. (2000). Concurrent gonococcal and chlamydial infection: how best to treat. Drugs 59, 80113.[ISI][Medline]
2 . Lind, I. (1997). Antimicrobial resistance in Neisseria gonorrhoeae. Clinical Infectious Diseases 24, Suppl. 1, 937.[ISI][Medline]
3 . Dillon, J. A., Rubabaza, J. P., Benzaken, A. S., Sardinha, J. C., Li, H., Bandeira, M. G. et al. (2001). Reduced susceptibility to azithromycin and high percentages of penicillin and tetracycline resistance in Neisseria gonorrhoeae isolates from Manaus, Brazil, 1998. Sexually Transmitted Diseases 28, 5216.[ISI][Medline]
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Moodley, P., Pillay, C., Goga, R., Kharsany, A. B. & Sturm, A. W. (2001). Evolution in the trends of antimicrobial resistance in Neisseria gonorrhoeae isolated in Durban over a 5 year period: impact of the introduction of syndromic management. Journal of Antimicrobial Chemotherapy 48, 8539.
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Zarantonelli, L., Borthagaray, G., Lee, E. H. & Shafer, W. M. (1999). Decreased azithromycin susceptibility of Neisseria gonorrhoeae due to mtrR mutations. Antimicrobial Agents and Chemotherapy 43, 246872.
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Zarantonelli, L., Borthagaray, G., Lee, E. H., Veal, W. & Shafer, W. M. (2001). Decreased susceptibility to azithromycin and erythromycin mediated by a novel mtr(R) promoter mutation in Neisseria gonorrhoeae. Journal of Antimicrobial Chemotherapy 47, 6514.