Department of Clinical Pharmacology, Medical University Vienna, Vienna, Austria.
Pharmacology. 2012;90(5-6):281-7. doi: 10.1159/000342423. Epub 2012 Sep 28.
Although major impairment of activity at lower pH values has been reported for fluoroquinolones, acidification is a widely recommended practice for the prophylaxis and treatment of uncomplicated urinary tract infections (UTIs). Until now, there is little evidence for the influence of pH on the activity on other antimicrobial classes in urine.
Bacterial growth curves of Staphylococcus aureus (ATCC 29213), Klebsiella oxytoca (ATCC 700324), Proteus mirabilis (ATCC 14153), Escherichia coli (ATCC 25922) and Enterococcus faecalis (ATCC 29212) were performed in Mueller-Hinton broth and in pooled human urine with a pH of between 5.0 and 8.0. Bacterial killing of trimethoprim, fosfomycin, amikacin, colistin and ertapenem against the five strains (where appropriate) was determined consecutively at concentrations equal to the MIC.
While no difference in the bacterial growth of E. coli, S. aureus, P. mirabilis and K. oxytoca was observed at different pH values, bacterial growth of E. faecalis was significantly reduced at low pH. Acidification to pH 5 impaired the antimicrobial activity of all investigated antibiotics, i.e. the net effect of bacterial growth and killing resulted in increased colony-forming units/ml at the end of the experiment.
The present in vitro findings indicate that acidification of urine during the treatment of UTIs should be carefully considered. While growth curves of one strain supports the concept of therapeutic or prophylactic acidification during UTIs, the most common pathogen, E. coli, was not affected by low pH. Independent of the investigated strain or antibiotic, pH values below 6 lead to a reduction of antimicrobial activity.
虽然氟喹诺酮类药物在较低 pH 值时的活性会受到严重影响，但酸化仍是治疗和预防单纯性尿路感染（UTI）的常用方法。迄今为止，关于 pH 值对尿液中其他抗菌药物类别的活性影响的证据很少。
在 pH 值为 5.0 至 8.0 的 Mueller-Hinton 肉汤和混合人尿中，对金黄色葡萄球菌（ATCC 29213）、产酸克雷伯菌（ATCC 700324）、奇异变形杆菌（ATCC 14153）、大肠埃希菌（ATCC 25922）和粪肠球菌（ATCC 29212）进行细菌生长曲线实验。在适当情况下，连续测定浓度等于 MIC 的甲氧苄啶、磷霉素、阿米卡星、黏菌素和厄他培南对五种菌株的杀菌作用。
在不同 pH 值下，未观察到大肠埃希菌、金黄色葡萄球菌、奇异变形杆菌和产酸克雷伯菌的细菌生长有差异，但粪肠球菌的细菌生长在低 pH 值时明显减少。酸化至 pH 5 会削弱所有研究抗生素的抗菌活性，即细菌生长和杀菌的净效应导致实验结束时菌落形成单位/ml 增加。
本体外研究结果表明，在治疗 UTI 时应谨慎考虑尿液酸化。虽然一种菌株的生长曲线支持在 UTI 期间进行治疗或预防性酸化的概念，但最常见的病原体大肠埃希菌不受低 pH 值的影响。无论研究的菌株或抗生素如何，pH 值低于 6 都会导致抗菌活性降低。
