Biavasco F, Giovanetti E, Montanari M P, Lupidi R, Varaldo P E
Institute of Microbiology, University of Ancona Medical School, Italy.
J Antimicrob Chemother. 1991 Jan;27(1):71-9. doi: 10.1093/jac/27.1.71.
Forty-two clinical isolates belonging to ten species of staphylococci were studied for their ability to develop single-step resistance, in vitro, to glycopeptide antibiotics. Selection was attempted through separate exposure to four glycopeptides (vancomycin, teicoplanin, and two investigational semisynthetic derivatives of the latter, TD-A3 and CTA-A1) on agar containing 10 mg/l of the test drug. No survivors from any test strain were recovered after exposure to TD-A3 or CTA-A1. After exposure to vancomycin or teicoplanin, surviving clones were only recovered from strains of three species, Staphylococcus aureus, S. epidermidis, and S. haemolyticus. Emergence of resistant clones was easier to observe from strains of S. haemolyticus exposed to teicoplanin. When tested for susceptibility, many survivors exhibited vancomycin and teicoplanin MICs below the drug concentration used for in-vitro selection, probably due to an inoculum effect in the plating procedure. In particular, the vancomycin MICs did not exceed 8 mg/l for S. aureus and S. epidermidis clones, and reached 16 mg/l for some clones from a S. haemolyticus strain. Teicoplanin MICs did not exceed 8 mg/l for S. aureus clones, but reached 64 mg/l for some clones of S. epidermidis, and were particularly high (64 to greater than or equal to 128 mg/l) for most clones of S. haemolyticus. In contrast, against all clones selected from all three species, the MICs of TD-A3 and CTA-A1 did not exceed 2 and 4 mg/l, respectively. Morphological investigations indicated that the colonies of a highly resistant S. haemolyticus clone were smaller and more butyraceous in consistency than those of the parent strain. In transmission and scanning electron microscopy studies, this same S. haemolyticus clone showed a more irregular cell wall than the parent strain.
对属于十种葡萄球菌的42株临床分离株进行了研究，以考察它们在体外对糖肽类抗生素产生单步耐药性的能力。通过将它们分别暴露于含10mg/l受试药物的琼脂上的四种糖肽（万古霉素、替考拉宁以及替考拉宁的两种研究用半合成衍生物TD-A3和CTA-A1）来进行筛选。暴露于TD-A3或CTA-A1后，未从任何测试菌株中回收存活菌。暴露于万古霉素或替考拉宁后，仅从金黄色葡萄球菌、表皮葡萄球菌和溶血葡萄球菌这三种菌的菌株中回收了存活克隆。从暴露于替考拉宁的溶血葡萄球菌菌株中更容易观察到耐药克隆的出现。当进行药敏试验时，许多存活菌的万古霉素和替考拉宁MIC低于用于体外筛选的药物浓度，这可能是由于平板接种过程中的接种量效应。特别是，金黄色葡萄球菌和表皮葡萄球菌克隆的万古霉素MIC不超过8mg/l，而溶血葡萄球菌菌株的一些克隆的万古霉素MIC达到16mg/l。金黄色葡萄球菌克隆的替考拉宁MIC不超过8mg/l，但表皮葡萄球菌的一些克隆的替考拉宁MIC达到64mg/l，而溶血葡萄球菌的大多数克隆的替考拉宁MIC特别高（64至大于或等于128mg/l）。相比之下，对于从所有三种菌中选出的所有克隆，TD-A3和CTA-A1的MIC分别不超过2mg/l和4mg/l。形态学研究表明，一株高度耐药的溶血葡萄球菌克隆的菌落比亲本菌株的菌落更小且质地更油腻。在透射电子显微镜和扫描电子显微镜研究中，同一株溶血葡萄球菌克隆显示出比亲本菌株更不规则的细胞壁。
