Thouverez Michelle, Muller Arno, Hocquet Didier, Talon Daniel, Bertrand Xavier
Service d'Hygiène Hospitalière et d'Epidémiologie Moléculaire1 and Service de Bactériologie2, Centre Hospitalier Universitaire Jean Minjoz, Besançon, France.
J Med Microbiol. 2003 Sep;52(Pt 9):801-806. doi: 10.1099/jmm.0.05252-0.
The objective of this study was to investigate the relationship between molecular epidemiology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) over a period of 4 years. The antibiotype of all MRSA isolates that were identified during a yearly period of 3 months was determined; 50 consecutive non-replicate MRSA isolates were typed each year. Susceptibility rates to gentamicin, tobramycin and ofloxacin remained stable (95, 16 and 4 %, respectively). In contrast, the proportion of MRSA isolates susceptible to erythromycin increased progressively from 10.5 to 32.5 % (P < 0.001). PFGE analysis of genomic DNA from 200 isolates revealed the presence of 15 different clones. Two epidemic clones were identified, which contained 150 (clone A) and 28 (clone C) isolates. Non-epidemic strains were more frequently susceptible to ofloxacin (31.8 versus 1.1 %) and tobramycin (45.4 versus 16.8 %) than epidemic strains; those isolates that were susceptible to all antibiotics tested belonged to sporadic clones. The increase of erythromycin susceptibility within MRSA isolates was caused by the emergence of clone C. This study suggests that when selection pressure exerted by an antibiotic is insufficient (i.e. below a threshold level), fitness advantages play a predominant role in the dissemination of MRSA clones. The balance between the selection pressure exerted by antibiotics and the disadvantage of lower replication rates of resistant strains in the absence of antibiotics complicates the biological model of clonal dissemination of epidemic MRSA strains.
本研究的目的是调查耐甲氧西林金黄色葡萄球菌（MRSA）在4年期间的分子流行病学与抗生素敏感性之间的关系。确定了在每年3个月期间鉴定出的所有MRSA分离株的抗菌型；每年对50株连续且不重复的MRSA分离株进行分型。对庆大霉素、妥布霉素和氧氟沙星的敏感率保持稳定（分别为95%、16%和4%）。相比之下，对红霉素敏感的MRSA分离株比例从10.5%逐渐增加到32.5%（P<0.001）。对200株分离株的基因组DNA进行PFGE分析，发现存在15种不同的克隆。鉴定出两个流行克隆，分别包含150株（克隆A）和28株（克隆C）分离株。非流行菌株比流行菌株对氧氟沙星（31.8%对1.1%）和妥布霉素（45.4%对16.8%）更敏感；那些对所有测试抗生素敏感的分离株属于散在克隆。MRSA分离株中红霉素敏感性的增加是由克隆C的出现引起的。本研究表明，当抗生素施加的选择压力不足（即低于阈值水平）时，适应性优势在MRSA克隆的传播中起主要作用。抗生素施加的选择压力与耐药菌株在无抗生素情况下较低复制率的劣势之间的平衡，使流行MRSA菌株克隆传播的生物学模型变得复杂。
