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不同浓度恩诺沙星、氟苯尼考、磷酸替米考星和泰拉霉素对溶血曼氏杆菌临床分离株的杀菌作用

Bactericidal effects of various concentrations of enrofloxacin, florfenicol, tilmicosin phosphate, and tulathromycin on clinical isolates of Mannheimia haemolytica.

作者信息

Blondeau Joseph M, Shebelski Shantelle D, Hesje Christine K

出版信息

Am J Vet Res. 2015 Oct;76(10):860-8. doi: 10.2460/ajvr.76.10.860.

Abstract

OBJECTIVE

To determine bactericidal effects of enrofloxacin, florfenicol, tilmicosin, and tulathromycin on clinical isolates of Mannheimia haemolytica at various bacterial densities and drug concentrations.

SAMPLE

4 unique isolates of M haemolytica recovered from clinically infected cattle.

PROCEDURES

Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) were determined for each drug and isolate. Mannheimia haemolytica suspensions (10(6) to 10(9) CFUs/mL) were exposed to the determined MIC and MPC and preestablished maximum serum and tissue concentrations of each drug. Log10 reduction in viable cells (percentage of cells killed) was measured at various points.

RESULTS

Bacterial killing at the MIC was slow and incomplete. After 2 hours of isolate exposure to the MPC and maximum serum and tissue concentrations of the tested drugs, 91% to almost 100% cell killing was achieved with enrofloxacin, compared with 8% growth to 93% cell killing with florfenicol, 199% growth to 63% cell killing with tilmicosin, and 128% growth to 43% cell killing with tulathromycin over the range of inoculum tested. For all drugs, killing of viable organisms was evident at all bacterial densities tested; however, killing was more substantial at the MPC and maximum serum and tissue drug concentrations than at the MIC and increased with duration of drug exposure. Rank order of drugs by killing potency was enrofloxacin, florfenicol, tilmicosin, and tulathromycin.

CONCLUSIONS AND CLINICAL RELEVANCE

Findings suggested that antimicrobial doses that equaled or exceeded the MPC provided rapid killing of M haemolytica by the tested drugs, decreasing opportunities for antimicrobial-resistant subpopulations of bacteria to develop during drug exposure.

摘要

目的

确定恩诺沙星、氟苯尼考、替米考星和泰拉霉素在不同细菌密度和药物浓度下对溶血曼氏杆菌临床分离株的杀菌效果。

样本

从临床感染牛中分离出的4株独特的溶血曼氏杆菌菌株。

步骤

测定每种药物和分离株的最低抑菌浓度(MIC)和防突变浓度(MPC)。将溶血曼氏杆菌悬液(10⁶至10⁹CFU/mL)暴露于所测定的MIC、MPC以及每种药物预先确定的最大血清和组织浓度下。在不同时间点测量活菌的Log10减少量(被杀灭细胞的百分比)。

结果

在MIC浓度下细菌杀灭缓慢且不完全。在分离株暴露于MPC以及所测试药物的最大血清和组织浓度2小时后,恩诺沙星实现了91%至几乎100%的细胞杀灭,相比之下,氟苯尼考导致8%的生长至93%的细胞杀灭,替米考星导致199%的生长至63%的细胞杀灭,泰拉霉素导致128%的生长至43%的细胞杀灭,涵盖所测试的接种物范围。对于所有药物,在所测试的所有细菌密度下均可观察到活菌杀灭;然而,在MPC以及最大血清和组织药物浓度下的杀灭比在MIC时更显著,并且随着药物暴露时间的延长而增加。按杀菌效力排列的药物顺序为恩诺沙星、氟苯尼考、替米考星和泰拉霉素。

结论及临床意义

研究结果表明,等于或超过MPC的抗菌剂量可使所测试药物快速杀灭溶血曼氏杆菌,减少药物暴露期间细菌耐药亚群产生的机会。

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