Aktaş Gülseren, Bozdoğan Bülent, Derbentli Sengül
İstanbul University Faculty of İstanbul Medicine, Department of Medical Microbiology, İstanbul, Turkey.
Mikrobiyol Bul. 2012 Jul;46(3):359-65.
The incidence of infections caused by multidrug resistant gram-positive bacteria is increasing worlwide. In addition, emergence and dissemination of glycopeptide resistance in enterococci has accelerated the need for the development of new antimicrobial agents for treatment. Linezolid which is an oxazolidinone and dalbavancin which is a second-generation, semi-synthetic lipoglycopeptid are important therapeutic options for infections caused by antimicrobial-resistant gram-positive pathogens. The aim of this study was to investigate the in-vitro antimicrobial activity of linezolid and dalbavancin against vancomycin- resistant enterococci (VRE). A total of 100 VRE strains, isolated from rectal swabs of patients hospitalized in Istanbul University Faculty of Istanbul Medicine between 2006-2007 were included in the study. All strains were identified as Enterococcus spp. by conventional methods and had minimum inhibitory concentrations (MICs) of ≥ 32 µg/ml for vancomycin. Vancomycin, linezolid and dalbavancin susceptibility testing was performed by broth microdilution method. For the quality control of the tests, S.aureus ATCC 29213 and E.faecalis ATCC 29212 were included in each run. Molecular identification of linezolid-resistant strains (n= 2) were done by 16S rRNA sequencing and resistance mechanisms were tested by 23S rRNA sequencing. Against VRE strains, MIC50, MIC90 and MIC ranges of linezolid and dalbavancin were found as 4, 4, 1-16 µg/ml and 32, 64, 0.25-128 µg/ml, respectively. Linezolid susceptibility, intermediate susceptibility and resistance rates were found as 32%, 66% and 2% in the same order. Linezolid-resistant two strains were identified as E.faecium, and this data was confirmed by Pasteur Institute. Both of those isolates had G2576T mutations in 23S rRNA genes. Because susceptibility breakpoint for dalbavancin has not been established by Clinical and Laboratory Standards Institute (CLSI) yet, susceptibility and resistance rates for dalbavancin were not indicated. According to the MIC results, linezolid was found to be the most effective antibiotic against VRE strains, and dalbavancin was found more effective than vancomycin. Additionally, our results showed that routine susceptibility testing of VRE strains isolated from hospitalized patients to linezolid was required.
耐多药革兰氏阳性菌引起的感染发病率在全球范围内呈上升趋势。此外,肠球菌中糖肽类耐药性的出现和传播加速了开发新型抗菌药物用于治疗的需求。利奈唑胺(一种恶唑烷酮类药物)和达巴万星(一种第二代半合成脂糖肽类药物)是治疗由耐抗菌药物革兰氏阳性病原体引起的感染的重要治疗选择。本研究的目的是调查利奈唑胺和达巴万星对万古霉素耐药肠球菌(VRE)的体外抗菌活性。本研究纳入了2006年至2007年间从伊斯坦布尔大学医学院住院患者直肠拭子中分离出的100株VRE菌株。所有菌株通过常规方法鉴定为肠球菌属,对万古霉素的最低抑菌浓度(MIC)≥32μg/ml。采用肉汤微量稀释法进行万古霉素、利奈唑胺和达巴万星的药敏试验。每次试验均纳入金黄色葡萄球菌ATCC 29213和粪肠球菌ATCC 29212作为质量控制。对利奈唑胺耐药菌株(n = 2)进行16S rRNA测序进行分子鉴定,并通过23S rRNA测序检测耐药机制。针对VRE菌株,利奈唑胺和达巴万星的MIC50、MIC90和MIC范围分别为4、4、1 - 16μg/ml和32、64、0.25 - 128μg/ml。利奈唑胺的敏感率(32%)、中介敏感率(66%)和耐药率(2%)依次为上述结果。两株利奈唑胺耐药菌株鉴定为屎肠球菌,该数据得到巴斯德研究所的证实。这两株分离株的23S rRNA基因均有G2576T突变。由于临床和实验室标准协会(CLSI)尚未确定达巴万星的药敏折点,因此未给出达巴万星的敏感率和耐药率。根据MIC结果,利奈唑胺被发现是对抗VRE菌株最有效的抗生素,达巴万星比万古霉素更有效。此外,我们的结果表明,对从住院患者中分离出的VRE菌株进行利奈唑胺常规药敏试验是必要的。