Shalit I, Welch D F, San Joaquin V H, Marks M I
Antimicrob Agents Chemother. 1985 Jun;27(6):908-11. doi: 10.1128/AAC.27.6.908.
Intraperitoneal antibiotics are used to treat Pseudomonas aeruginosa peritonitis, a serious complication of continuous ambulatory peritoneal dialysis. However, P. aeruginosa killing is often inefficient despite low MBCs. Broth dilution MIC/MBC and time kill curves of tobramycin, amikacin, netilmicin, azlocillin, piperacillin, ceftazidime, cefsulodin, and ciprofloxacin were determined in peritoneal dialysis fluid (PDF), buffered PDF, fluid recovered from patients on continuous ambulatory peritoneal dialysis (RPF), and cation-supplemented Mueller-Hinton broth. MBCs of all antibiotics were 8 to 16 times greater in PDF and RPF than in Mueller-Hinton broth or buffered PDF. Use of the time kill curve technique and Mueller-Hinton broth showed that aminoglycosides killed greater than or equal to 99.9% of P. aeruginosa at 1 h, ciprofloxacin killed greater than or equal to 99.9% at 2 h, and beta-lactams killed greater than or equal to 99.9% at 6 h. In contrast, killing was not demonstrated in PDF by any drug at 6 h and by aminoglycosides only at 24 h. Bactericidal activity was optimal in RPF for ciprofloxacin at 1 h and for aminoglycosides at 2 h; bactericidal activity was not demonstrated in RPF with any beta-lactam (no kill by penicillins; less than 99% kill by cephalosporins). Slow bacterial growth, increased protein binding, and glucose concentrations and other inhibitors may interfere with beta-lactam activity in RPF. These considerations and reported clinical failures and toxicity of aminoglycoside therapy warrant further study of quinolones and drug combinations in P. aeruginosa peritonitis.
腹腔内使用抗生素治疗铜绿假单胞菌腹膜炎,这是持续性非卧床腹膜透析的一种严重并发症。然而,尽管最低杀菌浓度(MBC)较低,但铜绿假单胞菌的杀灭效果往往不佳。在腹膜透析液(PDF)、缓冲腹膜透析液、持续性非卧床腹膜透析患者回收的液体(RPF)以及补充阳离子的穆勒-欣顿肉汤中,测定了妥布霉素、阿米卡星、奈替米星、阿洛西林、哌拉西林、头孢他啶、头孢磺啶和环丙沙星的肉汤稀释最低抑菌浓度/最低杀菌浓度以及时间杀菌曲线。所有抗生素在PDF和RPF中的MBC比在穆勒-欣顿肉汤或缓冲PDF中高8至16倍。使用时间杀菌曲线技术和穆勒-欣顿肉汤显示,氨基糖苷类抗生素在1小时时可杀灭≥99.9%的铜绿假单胞菌,环丙沙星在2小时时可杀灭≥99.9%,β-内酰胺类抗生素在6小时时可杀灭≥99.9%。相比之下,在PDF中,6小时时任何药物均未显示出杀菌效果,氨基糖苷类抗生素仅在24小时时显示出杀菌效果。环丙沙星在RPF中1小时时杀菌活性最佳,氨基糖苷类抗生素在2小时时最佳;在RPF中,任何β-内酰胺类抗生素均未显示出杀菌活性(青霉素无杀菌效果;头孢菌素杀菌率低于99%)。细菌生长缓慢、蛋白结合增加、葡萄糖浓度及其他抑制剂可能会干扰RPF中β-内酰胺类抗生素的活性。这些因素以及氨基糖苷类治疗已报道的临床失败案例和毒性,使得有必要进一步研究喹诺酮类药物及联合用药在铜绿假单胞菌腹膜炎中的应用。