Smith Patrick F, Booker Brent M, Ogundele Abayomi B, Kelchin Pamela
Applied Pharmacodynamics Laboratory, University at Buffalo School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY 14260, USA.
Diagn Microbiol Infect Dis. 2005 Jul;52(3):255-9. doi: 10.1016/j.diagmicrobio.2005.02.015.
Our objective was to evaluate and compare the in vitro activity of daptomycin, linezolid, and quinupristin/dalfopristin against clinical bloodstream isolates of Gram-positive pathogens from a large cancer center in the Northeastern United States. Minimum inhibitory concentrations (MICs) were determined for daptomycin, quinupristin/dalfopristin, and linezolid against 258 isolates; bactericidal activity was evaluated using time-kill experiments against 14 representative pathogens. Vancomycin-resistant enterococci represented the largest proportion of bacteria tested (32% of the isolates), followed by methicillin-resistant coagulase-negative staphylococci (23%), and vancomycin sensitive enterococci (14%). Against staphylococci, the MIC90 was 1 microg/mL for both daptomycin and quinupristin/dalfopristin and 4 microg/mL for linezolid. Against enterococci, the MIC90 for both daptomycin and linezolid was 4 microg/mL and was 16 microg/mL for quinupristin/dalfopristin. The quinupristin/dalfopristin MIC90 for Enterococcus faecium was 2 microg/mL. Two enterococci were linezolid resistant and remained susceptible to daptomycin. In vitro time-kill studies found daptomycin to be rapidly bactericidal against the majority of organisms tested, killing 99.9% of bacteria within 6 h. Quinupristin/dalfopristin was bactericidal against staphylococci and bacteriostatic against most enterococci. Linezolid was bacteriostatic against all organisms evaluated. Daptomycin, quinupristin/dalfopristin, and linezolid each demonstrated in vitro activity against this collection of organisms. Future clinical studies to evaluate a potential role for these agents in the management of infections in cancer patients, including the treatment of febrile neutropenia, appear warranted.
我们的目标是评估并比较达托霉素、利奈唑胺和奎奴普丁/达福普汀对美国东北部一家大型癌症中心临床血流分离出的革兰氏阳性病原体的体外活性。测定了达托霉素、奎奴普丁/达福普汀和利奈唑胺对258株分离菌的最低抑菌浓度(MIC);通过对14种代表性病原体进行时间-杀菌实验评估杀菌活性。耐万古霉素肠球菌在测试细菌中占比最大(占分离菌的32%),其次是耐甲氧西林凝固酶阴性葡萄球菌(23%)和万古霉素敏感肠球菌(14%)。对于葡萄球菌,达托霉素和奎奴普丁/达福普汀的MIC90均为1微克/毫升,利奈唑胺为4微克/毫升。对于肠球菌,达托霉素和利奈唑胺的MIC90均为4微克/毫升,奎奴普丁/达福普汀为16微克/毫升。粪肠球菌的奎奴普丁/达福普汀MIC90为2微克/毫升。有两株肠球菌对利奈唑胺耐药,但对达托霉素仍敏感。体外时间-杀菌研究发现,达托霉素对大多数测试菌具有快速杀菌作用,在6小时内可杀灭99.9% 的细菌。奎奴普丁/达福普汀对葡萄球菌具有杀菌作用,对大多数肠球菌具有抑菌作用。利奈唑胺对所有评估的菌株均具有抑菌作用。达托霉素、奎奴普丁/达福普汀和利奈唑胺均对这组菌株表现出体外活性。未来有必要开展临床研究,以评估这些药物在癌症患者感染管理中的潜在作用,包括治疗发热性中性粒细胞减少症。