Delpech Pierre, ALeryan Muna, Jones Brian, Gemmell Curtis, Lang Sue
Department of Life Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, UK.
Consultant Medical Microbiologist and Head of Microbiology, NHS Greater Glasgow and Clyde, Glasgow Royal Infirmary, 84 Castle Street, Glasgow, G4 0SF, UK.
Diagn Microbiol Infect Dis. 2018 May;91(1):93-97. doi: 10.1016/j.diagmicrobio.2018.01.006. Epub 2018 Jan 10.
Skin and soft tissue infections (SSTI) are among the most commonly occurring infections and evidence suggests that these are increasing world-wide. The aetiology is diverse, but Staphylococcus aureus predominate and these are often resistant to antimicrobials that were previously effective. Tedizolid is a new oxazolidinone-class antibacterial indicated for the treatment of adults with SSTI caused by Gram-positive pathogens, including S. aureus. The aim of this study was to evaluate the in vitro efficacy of tedizolid in comparison to other clinically used antibacterials against antibiotic sensitive- and resistant-staphylococci, grown in planktonic cultures and as biofilms reflecting the growth of the microorganism during episodes of SSTI. Against a panel of 66 clinical staphylococci, sensitivity testing revealed that a lower concentration of tedizolid was required to inhibit the growth of staphylococci compared to linezolid, vancomycin and daptomycin; with the tedizolid MIC being 8-fold (S. aureus) or 4-fold (S. epidermidis) below that obtained for linezolid. In addition, cfr+ linezolid-resistant strains remained fully susceptible to tedizolid. Against S. aureus biofilms, 10×MIC tedizolid was superior or comparable with 10×MIC comparator agents in activity, and superior to 10×MIC linezolid against those formed by S. epidermidis (65 vs. 33% reduction, respectively). Under flow-conditions both oxazolidinones at 10×MIC statistically out-performed vancomycin in their ability to reduce the viable cell count within a S. aureus biofilm with fewer the 12% of cells surviving compared to 63% of cells. In conclusion, tedizolid offers a realistic lower-dose alternative agent to treat staphylococcal SSTI, including infections caused by multi-drug resistant strains.
皮肤和软组织感染(SSTI)是最常见的感染类型之一,有证据表明其在全球范围内呈上升趋势。病因多种多样,但金黄色葡萄球菌最为常见,且这些感染往往对以前有效的抗菌药物产生耐药性。特地唑胺是一种新型恶唑烷酮类抗菌药物,用于治疗由革兰氏阳性病原体引起的成人SSTI,包括金黄色葡萄球菌。本研究的目的是评估特地唑胺与其他临床使用的抗菌药物相比,对浮游培养物和生物膜中生长的抗生素敏感和耐药葡萄球菌的体外疗效,生物膜反映了SSTI发作期间微生物的生长情况。对66株临床葡萄球菌进行的敏感性测试显示,与利奈唑胺、万古霉素和达托霉素相比,抑制葡萄球菌生长所需的特地唑胺浓度更低;特地唑胺的最低抑菌浓度(MIC)比利奈唑胺低8倍(金黄色葡萄球菌)或4倍(表皮葡萄球菌)。此外,携带cfr +基因的利奈唑胺耐药菌株对特地唑胺仍完全敏感。对于金黄色葡萄球菌生物膜,10倍MIC的特地唑胺在活性上优于或相当于10倍MIC的对照药物,并且在抑制表皮葡萄球菌形成的生物膜方面优于10倍MIC的利奈唑胺(分别减少65%和33%)。在流动条件下,两种10倍MIC的恶唑烷酮类药物在降低金黄色葡萄球菌生物膜内活菌数量方面在统计学上优于万古霉素,存活细胞少于12%,而万古霉素处理组为63%。总之,特地唑胺为治疗葡萄球菌性SSTI提供了一种切实可行的低剂量替代药物,包括由多重耐药菌株引起的感染。