接种量对耐甲氧西林金黄色葡萄球菌体外对万古霉素、达托霉素和利奈唑胺耐药性选择的影响。
The effect of inoculum size on selection of in vitro resistance to vancomycin, daptomycin, and linezolid in methicillin-resistant Staphylococcus aureus.
作者信息
Rio-Marques Laura, Hartke Axel, Bizzini Alain
机构信息
1 Service of Infectious Diseases, University of Lausanne, University Hospital Center (CHUV) , Lausanne, Switzerland .
出版信息
Microb Drug Resist. 2014 Dec;20(6):539-43. doi: 10.1089/mdr.2014.0059.
OBJECTIVES
The inoculum effect (IE) is an increase in the minimum inhibitory concentration (MIC) at high bacterial densities. The effect of three inoculum sizes on the selection of resistance to vancomycin, daptomycin, and linezolid was investigated in methicillin-resistant Staphylococcus aureus (MRSA).
METHODS
Low (10(4) CFU/ml), medium (10(6) CFU/ml), and high (10(8) CFU/ml) inocula of MRSA were exposed to twofold increasing concentrations of either drug during 15 days of cycling. MICs for low (MICL), medium (MICM), and high (MICH) inocula were determined daily. Conventional MICs were measured at days 1, 5, 10, and 15. Experiments were performed in triplicate.
RESULTS
At the beginning of the experiment a small IE was observed for vancomycin (MICL=1 μg/ml, MICM=1-2 μg/ml, and MICH=2 μg/ml) and a significant IE for daptomycin (MICL=0.25 μg/ml, MICM=0.25-0.5 μg/ml, and MICH=2 μg/ml). Linezolid exhibited no IE at low and medium inocula (MICL=1 μg/ml and MICM=1-2 μg/ml), but with the high inoculum, concentrations up to 2,048 μg/ml did not fully inhibit visual growth. During cycling, increase of MIC was observed for all antibiotics. At day 15, MICL, MICM, and MICH of vancomycin were 2-4, 4-8, and 4-16 μg/ml and of daptomycin were 0.5-2, 8-128, and 64-256 μg/ml, respectively. MICL and MICM of linezolid were 1 and 2-4 μg/ml, respectively. Conventional MICs showed vancomycin and daptomycin selection of resistance since day 5 depending on the inocula. No selection of linezolid resistance was observed.
CONCLUSIONS
Our results showed the importance of the inoculum size in the development of resistance. Measures aimed at lowering the inoculum at the site of infection should be used whenever possible in parallel to antimicrobial therapy.
目的
接种物效应（IE）是指在高细菌密度下最低抑菌浓度（MIC）升高。本研究在耐甲氧西林金黄色葡萄球菌（MRSA）中，研究了三种接种量对万古霉素、达托霉素和利奈唑胺耐药性选择的影响。
方法
将低（10⁴CFU/ml）、中（10⁶CFU/ml）、高（10⁸CFU/ml）接种量的MRSA在15天的循环过程中暴露于浓度呈两倍递增的上述任一种药物中。每天测定低接种量（MICL）、中接种量（MICM）和高接种量（MICH）的MIC。在第1、5、10和15天测量常规MIC。实验重复进行三次。
结果
在实验开始时，观察到万古霉素有较小的接种物效应（MICL = 1μg/ml，MICM = 1 - 2μg/ml，MICH = 2μg/ml），达托霉素有显著的接种物效应（MICL = 0.25μg/ml，MICM = 0.25 - 0.5μg/ml，MICH = 2μg/ml）。利奈唑胺在低接种量和中接种量时未表现出接种物效应（MICL = 1μg/ml，MICM = 1 - 2μg/ml），但在高接种量时，浓度高达2048μg/ml也不能完全抑制肉眼可见的生长。在循环过程中，所有抗生素的MIC均有升高。在第15天，万古霉素的MICL、MICM和MICH分别为2 - 4、4 - 8和4 - 16μg/ml，达托霉素的分别为0.5 - 2、8 - 128和64 - 256μg/ml。利奈唑胺的MICL和MICM分别为1和2 - 4μg/ml。常规MIC显示，自第5天起，万古霉素和达托霉素根据接种量选择耐药性。未观察到利奈唑胺耐药性的选择。
结论
我们的结果表明接种量大小在耐药性发展中的重要性。在进行抗菌治疗的同时，应尽可能采取措施降低感染部位的接种量。
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