Department of Pathogenic Biology, School of Basic Medical Science, Xinxiang Medical University, Xinxiang, China.
Xinxiang Key Laboratory of Pathogenic Biology, Xinxiang Medical University, Xinxiang, China.
Microb Drug Resist. 2022 Feb;28(2):229-235. doi: 10.1089/mdr.2021.0228. Epub 2021 Dec 1.
With the emergence of multidrug-resistant and pan-resistant strains, () shows higher treatment failure rates and mortality in clinics. It is more important to develop an effective method for treating infections. The main objectives of this study were to determine the minimal inhibitory concentration (MIC) and the mutant prevention concentration (MPC) for eight antimicrobial agents against isolated from different hosts and compare the emergence of resistant mutants between animal strains and human strains. A total of 72 nonduplicate isolates and 8 antimicrobial agents (amikacin, azithromycin, levofloxacin, doxycycline, nitrofurantoin, colistin, tigecycline, and imipenem) were used. The MIC and MPC values were determined using agar plate assays. The values of the selection index (SI) were calculated with MPC/MIC. Pharmacodynamic parameters were calculated using published plasma pharmacokinetic variables. For human isolate strains, the MPC (μg/mL) values were as follows: amikacin, 32/128; azithromycin, 64/128; levofloxacin, 4/16; doxycycline, 32/32; nitrofurantoin, 128/512; colistin, 4/8; tigecycline, 8/16; and imipenem, 4/8. The value of SI was 8 for azithromycin, doxycycline, and tigecycline; 16 for amikacin, levofloxacin, and nitrofurantoin; 4 for imipenem; and 2 for colistin. For animal isolate strains, the MPC values were 128 μg/mL for azithromycin and doxycycline, 64 μg/mL for amikacin, 32 μg/mL for levofloxacin, 512 μg/mL for nitrofurantoin, 8 μg/mL for colistin and tigecycline, 4 μg/mL for imipenem. The value of SI was 2 for colistin and imipenem, 8 for tigecycline, 16 for amikacin, and 32 for the other four agents. In combination with pharmacokinetic parameters, these findings indicated that the plasma concentrations of the seven antibiotics except imipenem were below the MPC for the entire dosing interval. The ability of eight antibiotics to prevent resistant mutants of was different between animal strains and human strains. Higher doses than those currently approved should be required to prevent the enrichment of mutants of drug-resistant bacteria in the clinics.
随着多药耐药和泛耐药菌株的出现， （ ）在临床上的治疗失败率和死亡率更高。因此，开发一种有效的治疗 感染的方法更为重要。本研究的主要目的是确定 8 种抗菌药物对来自不同宿主的 分离株的最小抑菌浓度（MIC）和突变预防浓度（MPC），并比较动物株和人株之间耐药突变体的出现情况。 共使用了 72 株非重复分离株和 8 种抗菌药物（阿米卡星、阿奇霉素、左氧氟沙星、多西环素、呋喃妥因、黏菌素、替加环素和亚胺培南）。采用琼脂平板法测定 MIC 和 MPC 值。用 MPC/MIC 计算选择指数（SI）值。使用已发表的血浆药代动力学变量计算药效学参数。 对于人源分离株，MPC（μg/mL）值如下：阿米卡星 32/128；阿奇霉素 64/128；左氧氟沙星 4/16；多西环素 32/32；呋喃妥因 128/512；黏菌素 4/8；替加环素 8/16；亚胺培南 4/8。SI 值为 8 的有阿奇霉素、多西环素和替加环素；16 的有阿米卡星、左氧氟沙星和呋喃妥因；4 的有亚胺培南；2 的有黏菌素。对于动物分离株，MPC 值为：阿奇霉素和多西环素 128μg/mL，阿米卡星 64μg/mL，左氧氟沙星 32μg/mL，呋喃妥因 512μg/mL，黏菌素和替加环素 8μg/mL，亚胺培南 4μg/mL。SI 值为 2 的有黏菌素和亚胺培南，8 的有替加环素，16 的有阿米卡星，4 的有其他四种药物。结合药代动力学参数，这些发现表明，除亚胺培南外，七种抗生素的血浆浓度在整个给药间隔内均低于 MPC。 八种抗生素预防 动物株和人株耐药突变体的能力不同。为了防止临床上耐药菌突变体的富集，需要使用高于目前批准的剂量。
