Opavski Natasa, Gajic Ina, Borek Anna L, Obszańska Katarzyna, Stanojevic Maja, Lazarevic Ivana, Ranin Lazar, Sitkiewicz Izabela, Mijac Vera
National Reference Laboratory for Streptococci, Medical Faculty, University of Belgrade, Dr Subotica starijeg 1, 11000 Belgrade, Serbia; Institute of Microbiology and Immunology, Medical Faculty, University of Belgrade, Dr Subotica starijeg 1, 11000 Belgrade, Serbia.
Department of Epidemiology and Clinical Microbiology, National Medicines Institute, Chełmska 30/34, 00-750 Warszawa, Poland.
Infect Genet Evol. 2015 Jul;33:246-52. doi: 10.1016/j.meegid.2015.05.011. Epub 2015 May 12.
A steady increase in macrolide resistance in Streptococcus pyogenes, group A streptococci (GAS) was reported in Serbia during 2004-2009 (9.9%). However, there are no data on the molecular epidemiology of pharyngeal macrolide resistance GAS (MRGAS) isolates. Therefore, the aims of this first nationwide study were to examine the prevalence of macrolide resistance in Serbian GAS and to determine their resistance phenotypes, genotypes and clonal relationships. Overall 3893 non-duplicate pharyngeal S. pyogenes isolates from outpatients with GAS infection were collected throughout country during 2008 and 2009. Among 486 macrolide resistant pharyngeal isolates collected, 103 were further characterized. Macrolide resistance phenotypes and genotypes were determined by double-disk diffusion test and PCR, respectively. Strain relatedness was determined by emm typing, multilocus sequence typing (MLST), multilocus variable tandem repeat analysis (MLVA), phage profiling (PP) and virulence factor profiling (VFP). Overall, macrolide resistance among GAS isolates in Serbia was 12.5%. M phenotype was the most common (71.8%), followed by iMLS (18.4%) and cMLS (9.7%). Three clonal complexes--emm75/mefA/ST49, emm12/mefA/ST36 and emm77/ermA/tetO/ST63 comprised over 90% of the tested strains. Although MLVA, PP and VFP distinguished 10, 20 and 12 different patterns, respectively, cluster analysis disclosed only small differences between strains which belonged to the same emm/ST type. Our data indicate dominance of three major internationally widely disseminated macrolide resistant clones and a high genetic homogeneity among the Serbian MRGAS population. Continued surveillance of macrolide resistance and clonal composition in MRGAS in Serbia in future is necessary to determine stability of MRGAS clones and to guide therapy strategies.
2004 - 2009年期间，塞尔维亚报告称A组链球菌（GAS），即化脓性链球菌对大环内酯类药物的耐药性稳步上升（9.9%）。然而，关于咽部大环内酯类耐药性GAS（MRGAS）分离株的分子流行病学尚无数据。因此，这项首次全国性研究的目的是检测塞尔维亚GAS中大环内酯类耐药性的流行情况，并确定其耐药表型、基因型和克隆关系。2008年至2009年期间，在全国范围内收集了3893株来自GAS感染门诊患者的非重复咽部化脓性链球菌分离株。在收集的486株大环内酯类耐药咽部分离株中，对103株进行了进一步特征分析。分别通过双碟扩散试验和PCR确定大环内酯类耐药表型和基因型。通过emm分型、多位点序列分型（MLST）、多位点可变串联重复分析（MLVA）、噬菌体谱分析（PP）和毒力因子谱分析（VFP）确定菌株相关性。总体而言，塞尔维亚GAS分离株中的大环内酯类耐药率为12.5%。M表型最为常见（71.8%），其次是iMLS（18.4%）和cMLS（9.7%）。三个克隆复合体——emm75/mefA/ST49、emm12/mefA/ST36和emm77/ermA/tetO/ST63占测试菌株的90%以上。尽管MLVA、PP和VFP分别区分出10种、20种和12种不同模式，但聚类分析显示属于同一emm/ST类型的菌株之间只有微小差异。我们的数据表明，三种主要的在国际上广泛传播的大环内酯类耐药克隆占主导地位，塞尔维亚MRGAS群体中存在高度的遗传同质性。未来有必要继续监测塞尔维亚MRGAS中大环内酯类耐药性和克隆组成，以确定MRGAS克隆的稳定性并指导治疗策略。
