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pH值和阳离子补充对体外抗生素后效应的影响。

Impact of pH and cationic supplementation on in vitro postantibiotic effect.

作者信息

Gudmundsson A, Erlendsdottir H, Gottfredsson M, Gudmundsson S

机构信息

Department of Internal Medicine, Borgarspitalinn, Reykjavik, Iceland.

出版信息

Antimicrob Agents Chemother. 1991 Dec;35(12):2617-24. doi: 10.1128/AAC.35.12.2617.

Abstract

Most studies on pharmacodynamic variables in vitro, including the postantibiotic effect (PAE), are performed at pH 7.4 in noncationic-supplemented media, a situation which may differ significantly from the true microenvironment in most infected foci. We studied the impact of five different pH levels (pH 5, 6, 7, 7.4, and 8) on the duration of the PAE, the MIC, and bactericidal activity. Acid pH was found to have in general a deleterious effect on the activity of aminoglycosides and ciprofloxacin against Escherichia coli and Pseudomonas aeruginosa, with the MIC being higher, the bactericidal rate being lower, and the PAE being shorter at pH 5 (and to a lesser extent at pH 6) than at more alkaline pH levels. Similar results were observed for imipenem against P. aeruginosa. The PAEs induced by ampicillin against E. coli and dicloxacillin against Staphylococcus aureus were not predictably dependent on the pH, whereas the PAEs induced by ciprofloxacin against S. aureus were longest at either end of the pH spectrum. The bactericidal activity of these agents was, however, pH dependent, being slower at acid pHs. The addition of 50 mg of Ca2+ and 20 mg of Mg2+ per liter of liquid medium at pH 7.4 did not affect the duration of the PAE. Since the pH in abscess cavities may be close to 5, these observations may be of importance for employment of the agents studied in closed or poorly drained infections.

摘要

大多数关于体外药效学变量的研究,包括抗生素后效应(PAE),都是在pH 7.4的无阳离子补充培养基中进行的,这种情况可能与大多数感染病灶的真实微环境有很大差异。我们研究了五种不同pH水平(pH 5、6、7、7.4和8)对PAE持续时间、最低抑菌浓度(MIC)和杀菌活性的影响。发现酸性pH总体上对氨基糖苷类药物和环丙沙星针对大肠杆菌和铜绿假单胞菌的活性有有害影响,与碱性更强的pH水平相比,在pH 5时(在较小程度上在pH 6时)MIC更高、杀菌率更低且PAE更短。对于亚胺培南针对铜绿假单胞菌的情况也观察到了类似结果。氨苄西林针对大肠杆菌以及双氯西林针对金黄色葡萄球菌所诱导的PAE并非可预测地依赖于pH,而环丙沙星针对金黄色葡萄球菌所诱导的PAE在pH范围的两端最长。然而,这些药物的杀菌活性是pH依赖性的,在酸性pH下较慢。在pH 7.4的液体培养基中每升添加50 mg的Ca2+和20 mg的Mg2+并不影响PAE的持续时间。由于脓肿腔内的pH可能接近5,这些观察结果对于在闭合性或引流不畅的感染中使用所研究的药物可能具有重要意义。

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