Sieradzki K, Villari P, Tomasz A
The Rockefeller University, New York, New York 10021, USA.
Antimicrob Agents Chemother. 1998 Jan;42(1):100-7. doi: 10.1128/AAC.42.1.100.
Of 41 methicillin-resistant coagulase-negative staphylococcal clinical isolates collected during a 5-month period between late 1995 and early 1996, 28 showed tube dilution teicoplanin MICs of 4 to 8 microg/ml which increased to 16 to 32 microg/ml upon prolonged incubation. Cultures of such bacteria were heterogeneous; they contained subpopulations with frequencies of 10(-5) to 10(-4) that could grow on up to 50 microg of teicoplanin per ml. The same cultures were also heterogeneous with respect to susceptibility to vancomycin; while the MICs for the majority of cells were 2 to 4 microg/ml, subpopulations that could grow on 6 to 12 microg of vancomycin per ml were also present at frequencies of 10(-5) to 10(-7). Selective enrichment of such cultures for the resistant subpopulation occurred with relative ease under laboratory conditions. Heterogeneous phenotypes for teicoplanin (but not for vancomycin) susceptibility were also identified in several Staphylococcus epidermidis isolates collected during the preantibiotic era. The addition of half the MIC of teicoplanin inhibited autolysis and caused formation of cellular aggregates which disintegrated to individual bacteria in the stationary phase when the titer of teicoplanin in the medium fell to undetectable levels, indicating removal of the antibiotic from the culture medium by the bacteria.
在1995年末至1996年初的5个月期间收集的41株耐甲氧西林凝固酶阴性葡萄球菌临床分离株中,28株的试管稀释替考拉宁MIC为4至8微克/毫升,延长培养后增至16至32微克/毫升。此类细菌培养物具有异质性;它们含有频率为10^(-5)至10^(-4)的亚群,这些亚群能够在每毫升高达50微克的替考拉宁上生长。相同的培养物对万古霉素的敏感性也具有异质性;虽然大多数细胞的MIC为2至4微克/毫升,但能够在每毫升6至12微克万古霉素上生长的亚群也以10^(-5)至10^(-7)的频率存在。在实验室条件下,相对容易地对这些培养物进行抗性亚群的选择性富集。在抗生素前时代收集的几株表皮葡萄球菌分离株中也鉴定出替考拉宁(但不是万古霉素)敏感性的异质表型。添加一半MIC的替考拉宁可抑制自溶并导致细胞聚集体形成,当培养基中替考拉宁的滴度降至无法检测的水平时,这些聚集体在稳定期分解为单个细菌,表明细菌从培养基中去除了抗生素。