Yang Luo, Wang Kunjie, Li Hong, Denstedt John D, Cadieux Peter A
Division of Urology, Department of Surgery, No. 4 West China Teaching Hospital, Sichuan University, Chengdu, P.R. China; Division of Urology, Department of Surgery, Western University, London, Canada; Department of Urology of West China Hospital of Sichuan University, Chengdu, P.R. China.
Department of Urology of West China Hospital of Sichuan University, Chengdu, P.R. China.
Urology. 2014 Sep;84(3):731.e1-7. doi: 10.1016/j.urology.2014.04.048.
To determine the effects of pH on the activity of clinically relevant antibiotics against bacterial uropathogens. Numerous factors affect antibiotic efficacy within the urinary tract including pH. Because human urine can substantially vary from acidic (pH 4.5) to alkaline (pH 8) conditions and can be easily clinically manipulated, it would be a great advantage to better understand the role of pH in antibiotic treatment of urinary tract infection.
This in vitro study investigated the activity of 24 widely used antimicrobial agents against bacterial strains comprising 6 major uropathogenic species (Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterococcus faecalis, Staphylococcus saprophyticus, and Staphylococcus epidermidis) over the range of pH 5-8. Standard disk-diffusion and broth-microdilution assays were used. One-way analysis of variance was applied to determine significance (P <.05).
For 18 of the 24 agents, pH was shown to play a significant role in overall inhibitory activity. Although most agents behaved similarly across most or all of the uropathogens tested, several only showed pH-dependent effects against certain organisms. The fluoroquinolones, co-trimoxazole, aminoglycosides, and macrolides all functioned optimally at alkaline pH, whereas the tetracyclines, nitrofurantoin, and many of the β-lactams tested exhibited their highest activity under more acidic conditions. Sulfamethoxazole, oxacillin, amoxicillin and clavulanic acid, vancomycin, imipenem, and clindamycin were largely unaffected by pH.
Clinicians should consider the urinary pH of their patients when treating urinary tract infection, especially in complicated scenarios. Future clinical investigations examining urinary pH and antibiotic efficacy may result in the application of decreased antibiotic dosages and regimen durations, potentially reducing antibiotic resistance development.
确定pH值对临床相关抗生素抗尿路致病菌活性的影响。包括pH值在内的众多因素会影响尿路内抗生素的疗效。由于人类尿液的pH值可在酸性(pH 4.5)至碱性(pH 8)之间大幅变化,且在临床上易于调控,因此更好地了解pH值在尿路感染抗生素治疗中的作用将具有很大优势。
本体外研究考察了24种广泛使用的抗菌药物对包含6种主要尿路致病菌种(大肠杆菌、肺炎克雷伯菌、奇异变形杆菌、粪肠球菌、腐生葡萄球菌和表皮葡萄球菌)的细菌菌株在pH 5 - 8范围内的活性。采用标准纸片扩散法和肉汤微量稀释法。应用单因素方差分析确定显著性(P <.05)。
在24种药物中,有18种显示pH值在总体抑制活性中起重要作用。尽管大多数药物在大多数或所有测试的尿路致病菌中表现相似,但有几种仅对某些生物体显示出pH依赖性效应。氟喹诺酮类、复方新诺明、氨基糖苷类和大环内酯类在碱性pH条件下功能最佳,而四环素类、呋喃妥因以及许多测试的β - 内酰胺类在酸性更强的条件下表现出最高活性。磺胺甲恶唑、苯唑西林、阿莫西林和克拉维酸、万古霉素、亚胺培南和克林霉素在很大程度上不受pH值影响。
临床医生在治疗尿路感染时应考虑患者的尿液pH值,尤其是在复杂情况下。未来关于尿液pH值和抗生素疗效的临床研究可能会导致抗生素剂量和疗程的减少,从而可能降低抗生素耐药性的产生。