School of Pharmacy, Queen's University Belfast, Belfast, UK.
J Appl Microbiol. 2013 Aug;115(2):382-9. doi: 10.1111/jam.12241. Epub 2013 May 28.
To examine the effect of elevated pH, as reported during urinary catheter infections, on quinolone activity against the urease-producing pathogen Proteus mirabilis.
Susceptibility of Pr. mirabilis to nalidixic acid, norfloxacin and ciprofloxacin was examined in media of pH 5 to pH 10 by determination of MICs, MBCs, minimum biofilm eradication concentrations (MBECs) and time-kill assays. Elevation of media pH from 5 to 9 caused a 10-fold decrease in bacteriostatic activity of nalidixic acid and was also associated with loss of the characteristic 'paradoxical' bactericidal activity. Alkaline pH, however, increased both bacteriostatic and bactericidal activities of the two fluoroquinolones tested against both planktonic and biofilm-associated Pr. mirabilis; MBC and MBEC values for ciprofloxacin decreased approx. 6000-fold and 10-fold, respectively, between pH 5 and pH 9. Rates of kill of all three agents were most rapid at pH 7, the optimal pH for bacterial replication.
pH has a pronounced effect on quinolone-mediated killing, which may be attributed to the dependence of cellular uptake on quinolone ionization state.
These results provide rationale for the use of these agents for Pr. mirabilis eradication in alkaline environments, including urinary catheter infections: the incidence, recurrence and recalcitrance of which pose a significant burden to healthcare providers.
研究尿液导管感染时报告的 pH 值升高对产脲酶病原体奇异变形杆菌中喹诺酮类药物活性的影响。
通过测定 MIC、MBC、最低生物膜清除浓度 (MBEC) 和时间杀伤试验，在 pH 值为 5 至 10 的培养基中检查奇异变形杆菌对萘啶酸、诺氟沙星和环丙沙星的敏感性。将培养基 pH 值从 5 升高到 9 导致萘啶酸的抑菌活性降低 10 倍，并且还与特征性的“反常”杀菌活性丧失有关。然而，碱性 pH 值增加了两种氟喹诺酮类药物对浮游生物和生物膜相关奇异变形杆菌的抑菌和杀菌活性；环丙沙星的 MBC 和 MBEC 值在 pH 5 和 pH 9 之间分别降低了约 6000 倍和 10 倍。所有三种药物的杀灭速率在 pH 值为 7 时最快，这是细菌复制的最佳 pH 值。
pH 值对喹诺酮类药物介导的杀伤有显著影响，这可能归因于细胞摄取对喹诺酮类药物离子化状态的依赖性。
这些结果为在碱性环境中使用这些药物根除奇异变形杆菌提供了依据，包括尿液导管感染：奇异变形杆菌的发病率、复发率和难治性给医疗保健提供者带来了巨大负担。
