Antimicrobial susceptibility/resistance and NG-MAST characterisation of Neisseria gonorrhoeae in Belarus, Eastern Europe, 2010–2013

BMC Infectious Diseases

Magnus Unemo⁵  Marius Domeika¹  Aliaksandr Lukyanau⁶  Natallia Charniakova³  Irina Shimanskaya⁶  Slavyana Glazkova²  Nataliya Pankratava⁴  Leonid Titov²  Daniel Golparian⁵  Fiodar Lebedzeu² 

[1] Department of Prevention and Control of Communicable Diseases, Uppsala County Council, Uppsala, Sweden;The Republican Research and Practical Center for Epidemiology and Microbiology (RRPCEM), Minsk, Belarus;Vitebsk Regional Dermato-Venerological Dispensary, Vitebsk, Belarus;Mogilev Regional Dermato-Venerological Dispensary, Mogilev, Belarus;WHO Collaborating Centre for Gonorrhoea and other Sexually Transmitted Infections, Swedish Reference Laboratory for Pathogenic Neisseria, Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden;Minsk City Dermato-Venerological Dispensary, Minsk, Belarus

关键词: Belarus;    N. gonorrhoeae multiantigen sequence typing (NG-MAST);    Treatment;    Cefixime;    Ceftriaxone;    Extended-spectrum cephalosporins (ESCs);    Surveillance;    Antimicrobial resistance;    Gonorrhoea;    Neisseria gonorrhoeae;   

Others  :  1120420
DOI  :  10.1186/s12879-015-0755-9

 received in 2014-10-15, accepted in 2015-01-15,  发布年份 2015

【 摘 要 】

Background

Gonorrhoea and widely spread antimicrobial resistance (AMR) in its etiological agent Neisseria gonorrhoeae are major public health concerns worldwide. Gonococcal AMR surveillance nationally and internationally, to identify emerging resistance and inform treatment guidelines, is imperative for public health purposes. In 2009, AMR surveillance was initiated in Belarus, Eastern Europe because no gonococcal AMR data had been available for at least two decades. Herein, the prevalence and trends of gonococcal AMR and molecular epidemiological characteristics of N. gonorrhoeae strains from 2010 to 2013 in Belarus, are described.

Methods

N. gonorrhoeae isolates (n=193) obtained in the Mogilev (n=142), Minsk (n=36) and Vitebsk (n=15) regions of Belarus in 2010 (n=72), 2011 (n=6), 2012 (n=75) and 2013 (n=40) were analyzed in regards to AMR using the Etest method and for molecular epidemiology with N. gonorrhoeae multi-antigen sequence typing (NG-MAST).

Results

During 2010–2013, the proportions of resistant N. gonorrhoeae isolates were as follows: tetracycline 36%, ciprofloxacin 28%, penicillin G 9%, azithromycin 5%, and cefixime 0.5%. Only one (0.5%) β-lactamase producing isolate was detected. No isolates resistant to ceftriaxone and spectinomycin were identified. Overall, the resistance levels to tetracycline, ciprofloxacin and penicillin G were relatively stable. Interestingly, the level of resistance to azithromycin declined from 12% in 2010 to 0% in 2013 (P < 0.05). In total, 70 NG-MAST STs were identified. The predominant STs were ST1993 (n=53), ST807 (n=13), ST285 (n=8) and ST9735 (n=8). Many novel STs (n=43, 61%), representing 41% of all isolates, were found.

Conclusions

During 2010–2013, the N. gonorrhoeae population in Belarus displayed high and relatively stable resistance levels to tetracycline, ciprofloxacin, and penicillin G, while the resistance to azithromycin declined. One isolate was resistant to cefixime, but no resistance to ceftriaxone or spectinomycin was found. The results of the present surveillance initiated in 2009 were also used to replace penicillin G with ceftriaxone (1 g single dose intramuscularly) as the first-line drug for empiric treatment of gonorrhoea in the national treatment guidelines in Belarus in late 2009. It is essential to further strengthen the surveillance of gonococcal AMR and ideally survey also treatment failures and molecular epidemiological genotypes in Belarus.

【 授权许可】

   
2015 Lebedzeu et al.; licensee BioMed Central.

【 图 表 】

Figure 1.

【 参考文献 】

• [1]European Centre for Disease Prevention and Control: Sexually Transmitted Infections in Europe 2012. ECDC, Stockholm; 2014.
• [2]Unemo M, Ison CA, Cole M, Spiteri G, van de Laar M, Khotenashvili L: Gonorrhoea and gonococcal antimicrobial resistance surveillance networks in the WHO European Region, including the independent countries of the former Soviet Union. Sex Transm Infect 2013, 89(Suppl 4):iv42-6.
• [3]Unemo M, Shipitsyna E, Domeika M: Recommended antimicrobial treatment of uncomplicated gonorrhoea in 2009 in 11 East European countries: implementation of a Neisseria gonorrhoeae antimicrobial susceptibility programme in this region is crucial. Sex Transm Infect 2010, 86:442-4.
• [4]Unemo M, Shipitsyna E, Domeika M: Gonorrhoea surveillance, laboratory diagnosis and antimicrobial susceptibility testing of Neisseria gonorrhoeae in 11 countries of the eastern part of the WHO European region. APMIS 2011, 119:643-9.
• [5]Unemo M, Shafer WM: Antimicrobial resistance in Neisseria gonorrhoeae in the 21st Century: past, evolution, and future. Clin Microbiol Rev 2014, 27:587-613.
• [6]Tapsall JW, Ndowa F, Lewis DA, Unemo M: Meeting the public health challenge of multidrug- and extensively drug-resistant Neisseria gonorrhoeae. Expert Rev Anti Infect Ther 2009, 7:821-34.
• [7]Lewis DA: The gonococcus fights back: is this time a knock out? Sex Transm Infect 2010, 86:415-21.
• [8]Unemo M, Nicholas RA: Emergence of multi-drug resistant, extensively drug-resistant and untreatable gonorrhea. Future Microbiol 2012, 7:1401-22.
• [9]Whiley DM, Goire N, Lahra MM, Donovan B, Limnios AE, Nissen MD, et al.: The ticking time bomb: escalating antibiotic resistance in Neisseria gonorrhoeae is a public health disaster in waiting. J Antimicrob Chemother 2012, 67:2059-61.
• [10]Bolan GA, Sparling PF, Wasserheit JN: The emerging threat of untreatable gonococcal infection. N Engl J Med 2012, 366:485-7.
• [11]Spiteri G, Cole M, Unemo M, Hoffmann S, Ison C, van de Laar M: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP)--a sentinel approach in the European Union (EU)/European Economic Area (EEA). Sex Transm Infect 2013, 89(Suppl 4):iv16-8.
• [12]Tapsall J, Read P, Carmody C, Bourne C, Ray S, Limnios A, et al.: Two cases of failed ceftriaxone treatment in pharyngeal gonorrhoea verified by molecular microbiological methods. J Med Microbiol 2009, 58:683-7.
• [13]Unemo M, Golparian D, Hestner A: Ceftriaxone treatment failure of pharyngeal gonorrhoea verified by international recommendations, Sweden, July 2010. Euro Surveill 2011, 16(6):19792.
• [14]Unemo M, Golparian D, Potocnik M, Jeverica S: Treatment failure of pharyngeal gonorrhoea with internationally recommended first-line ceftriaxone verified in Slovenia, September 2011. Euro Surveill 2012, 17(25):20200.
• [15]Ohnishi M, Golparian D, Shimuta K, Saika T, Hoshina S, Iwasaku K, et al.: Is Neisseria gonorrhoeae initiating a future era of untreatable gonorrhea?: detailed characterization of the first strain with high-level resistance to ceftriaxone. Antimicrob Agents Chemother 2011, 55:3538-45.
• [16]Chen YM, Stevens K, Tideman R, Zaia A, Tomita T, Fairley CK, et al.: Failure of ceftriaxone 500 mg to eradicate pharyngeal gonorrhoea, Australia. J Antimicrob Chemother 2013, 68:1445-7.
• [17]Read PJ, Limnios EA, McNulty A, Whiley D, Lahra LM: One confirmed and one suspected case of pharyngeal gonorrhoea treatment failure following 500 mg ceftriaxone in Sydney, Australia. Sex Health 2013, 10:460-2.
• [18]Golparian D, Ohlsson A, Janson H, Lidbrink P, Richtner T, Ekelund O, et al.: Four treatment failures of pharyngeal gonorrhoea with ceftriaxone (500 mg) or cefotaxime (500 mg), Sweden, 2013 and 2014. Euro Surveill 2014, 19(30):pii:20862.
• [19]World Health Organization (WHO), Department of Reproductive Health and Research: Global action plan to control the spread and impact of antimicrobial resistance in Neisseria gonorrhoeae. WHO, Geneva; 2012.
• [20]Ndowa F, Lusti-Narasimhan M, Unemo M: The serious threat of multidrug-resistant and untreatable gonorrhoea: the pressing need for global action to control the spread of antimicrobial resistance, and mitigate the impact on sexual and reproductive health. Sex Transm Infect 2012, 88:317-8.
• [21]European Centre for Disease Prevention and Control (ECDC): Response plan to control and manage the threat of multidrug-resistant gonorrhoea in Europe. ECDC, Stockholm; 2012.
• [22]Domeika M, Savicheva A, Sokolovskiy E, Ballard R, Unemo M: Eastern European Network for Sexual and Reproductive Health (EE SRH Network): Quality enhancements and quality assurance of laboratory diagnosis of sexually transmitted infections in Eastern Europe. Int J STD AIDS 2009, 20:365-7.
• [23]Unemo M, Fasth O, Fredlund H, Limnios A, Tapsall JW: Phenotypic and genetic characterization of the 2008 WHO Neisseria gonorrhoeae reference strain panel intended for global quality assurance and quality control of gonococcal antimicrobial resistance surveillance for public health purposes. J Antimicrob Chemother 2009, 63:1142-51.
• [24]Tapsall JW, Cheng JK: Rapid identification of pathogenic species of Neisseria by carbohydrate degradation tests: importance of glucose in media used for preparation of inocula. Br J Ven Dis 1981, 14:249-52.
• [25]Martin IM, Ison CA, Aanensen DM, Fenton KA, Spratt BG: Rapid sequence-based identification of gonococcal transmission clusters in a large metropolitan area. J Infect Dis 2004, 189:1497-505.
• [26]Unemo M, Dillon JA: Review and international recommendation of methods for typing Neisseria gonorrhoeae isolates and their implications for improved knowledge of gonococcal epidemiology, treatment, and biology. Clin Microbiol Rev 2011, 24:447-58.
• [27]Unemo M, Sjöstrand A, Akhras M, Gharizadeh B, Lindbäck E, Pourmand N, et al.: Molecular characterization of Neisseria gonorrhoeae identifies transmission and resistance of one ciprofloxacin-resistant strain. APMIS 2007, 115:231-41.
• [28]Glazkova S, Golparian D, Titov L, Pankratova N, Suhabokava N, Shimanskaya I, et al.: Antimicrobial susceptibility/resistance and molecular epidemiological characteristics of Neisseria gonorrhoeae in 2009 in Belarus. APMIS 2011, 119:537-42.
• [29]Ministry of Health in Belarus: Annex 2 to the Order of Health Ministry of October 29, 2009 № 1020 “Clinical diagnosis and treatment protocol of patients with sexually transmitted infections”. [In Russian]
• [30]Unemo M, Vorobieva V, Firsova N, Ababkova T, Leniv I, Haldorsen BC, et al.: The Neisseria gonorrhoeae population transmitted in Arkhangelsk, Russia in 2004 – phenotypic and genotypic heterogeneity. Clin Microbiol Infect 2007, 13:873-8.
• [31]Kubanova A, Kubanov A, Frigo N, Sidorenko S, Priputnevich T, Vachnina T, et al.: National surveillance of antimicrobial susceptibility in Neisseria gonorrhoeae in 2005–2006 and recommendations of first-line antimicrobial drugs for gonorrhoea treatment in Russia. Sex Transm Infect 2008, 84:285-9.
• [32]Kubanova A, Frigo N, Kubanov A, Sidorenko S, Lesnaya I, Polevshikova S, et al.: The Russian gonococcal antimicrobial susceptibility programme (RU-GASP) – national resistance prevalence in 2007 and 2008, and trends during 2005–2008. Euro Surveill 2010, 15(14):19533.
• [33]Kubanova A, Kubanov A, Frigo N, Solomka V, Semina V, Vorobyev D, et al.: Russian gonococcal antimicrobial susceptibility programme (RU-GASP) - resistance in Neisseria gonorrhoeae during 2009–2012 and NG-MAST genotypes in 2011 and 2012. BMC Infect Dis 2014, 14(1):342. BioMed Central Full Text
• [34]Palmer HM, Young H, Winter A, Dave J: Emergence and spread of azithromycin-resistant Neisseria gonorrhoeae in Scotland. J Antimicrob Chemother 2008, 62:490-4.
• [35]Chisholm SA, Dave J, Ison CA: High-level azithromycin resistance occurs in Neisseria gonorrhoeae as a result of a single point mutation in the 23S rRNA genes. Antimicrob Agents Chemother 2012, 54:3812-6.
• [36]Starnino S, Stefanelli P: Neisseria gonorrhoeae Italian Study Group I: Azithromycin-resistant Neisseria gonorrhoeae strains recently isolated in Italy. J Antimicrob Chemother 2009, 63:1200-4.
• [37]Galarza PG, Abad R, Canigia LF, Buscemi L, Pagano I, Oviedo C, et al.: New mutation in 23S rRNA gene associated with high level of azithromycin resistance in Neisseria gonorrhoeae. Antimicrob Agents Chemother 2010, 54:1652-3.
• [38]Katz AR, Komeya AY, Soge OO, Kiaha MI, Lee MV, Wasserman GM, et al.: Neisseria gonorrhoeae with high-level resistance to azithromycin: case report of the first isolate identified in the United States. Clin Infect Dis 2012, 54:841-3.
• [39]Unemo M, Golparian D, Hellmark B: First three Neisseria gonorrhoeae isolates with high-level resistance to azithromycin in Sweden: a threat to currently available dual-antimicrobial regimens for treatment of gonorrhea? Antimicrob Agents Chemother 2013, 58:624-5.
• [40]Jeverica S, Golparian D, Maticic M, Potočnik M, Mlakar B, Unemo M: Phenotypic and molecular characterization of Neisseria gonorrhoeae isolates from Slovenia, 2006–12: rise and fall of the multidrug-resistant NG-MAST genogroup 1407 clone? J Antimicrob Chemother 2014, 69:1517-25.
• [41]Mlynarczyk-Bonikowska B, Serwin AB, Golparian D, Walter de Walthoffen S, Majewski S, Koper M, et al.: Antimicrobial susceptibility/resistance and genetic characteristics of Neisseria gonorrhoeae isolates from Poland, 2010–2012. BMC Infect Dis 2014, 14(1):65. BioMed Central Full Text
• [42]Ison CA, Town K, Obi C, Chisholm S, Hughes G, Livermore DM, et al.: Decreased susceptibility to cephalosporins among gonococci: data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) in England and Wales, 2007–2011. Lancet Infect Dis 2013, 13:762-8.
• [43]Chisholm SA, Unemo M, Quaye N, Johansson E, Cole MJ, Ison CA, et al.: Molecular epidemiological typing within the European gonococcal antimicrobial resistance surveillance programme reveals predominance of a multidrug-resistant clone. Euro Surveill 2013, 18(3):20358.
• [44]Grad YH, Kirkcaldy RD, Trees D, Dordel J, Harris SR, Goldstein E, et al.: Genomic epidemiology of Neisseria gonorrhoeae with reduced susceptibility to cefixime in the USA: a retrospective observational study. Lancet Infect Dis 2014, 14:220-6.
• [45]Bala M, Kakran M, Singh V, Sood S, Ramesh V: Monitoring antimicrobial resistance in Neisseria gonorrhoeae in selected countries of the WHO South-East Asia Region between 2009 and 2012: a retrospective analysis. Sex Transm Infect 2013, 89(Suppl 4):iv28-35.