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To investigate comprehensively the antimicrobial susceptibility and resistance of Neisseria gonorrhoeae during 2005–2006 in a national survey and to recommend effective antimicrobial drugs for the treatment of gonorrhoea in Russia.The susceptibility of N gonorrhoeae isolates, cultured mainly from consecutive gonorrhoea patients (n = 1030) during the period January 2005 to December 2006 in Russia, to penicillin G, ceftriaxone, ciprofloxacin, tetracycline and spectinomycin was analysed using the agar dilution method. Nitrocefin discs were used for β-lactamase detection.All isolates were susceptible to ceftriaxone. During 2005 and 2006, however, 5%, 50%, 70% and 77% displayed intermediate susceptibility or resistance to spectinomycin, ciprofloxacin, tetracycline and penicillin G, respectively. Furthermore, 4% of the isolates were β-lactamase producing during these years. The different federal districts of Russia displayed substantial heterogeneities with regard to the prevalence of gonorrhoea and antimicrobial resistance among N gonorrhoeae isolates.In Russia, penicillins, ciprofloxacin, or tetracycline should definitively not be used in the empirical treatment of gonorrhoea. The recommended first-line antimicrobial drug should be ceftriaxone. If ceftriaxone is not available, spectinomycin ought to be used. Increasing levels of intermediate susceptibility and resistance to spectinomycin have, however, been observed during recent years and, accordingly, great care and monitoring should be undertaken when using this agent. Continuous local, national and international surveillance of N gonorrhoeae antimicrobial susceptibility, in order to reveal the emergence of new resistance, to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis, is crucial.