Figueredo V M, Neu H C
Department of Medicine, College of Physicians & Surgeons, Columbia University, New York.
J Antimicrob Chemother. 1988 Jul;22(1):41-50. doi: 10.1093/jac/22.1.41.
Pseudomonas aeruginosa remains the most common respiratory pathogen causing morbidity and mortality in cystic fibrosis (CF) patients. The in-vitro activity of ciprofloxacin and fosfomycin (calcium and tromethamine salts) in combination against P. aeruginosa isolates from CF patients, all of whom had received previous courses of ciprofloxacin, was evaluated by agar plate dilution chequerboard technique. The concentrations of drugs used were those that would be achieved in patients by oral and intravenous (fosfomycin only) routes. Synergy, taking into account fosfomycin concentrations achievable intravenously, was found against 60% of P. aeruginosa isolates. With concentrations achieved after an oral dose, 17% of isolates were synergistically inhibited. Time-kill experiments confirmed these findings. Ciprofloxacin MICs against resistant P. aeruginosa were reduced to achievable sputum and serum levels in the presence of fosfomycin. However, in progressive resistance studies fosfomycin failed to delay the development of resistance to ciprofloxacin. The combinations of ofloxacin/fosfomycin and ciprofloxacin/fosmidomycin were also tested, but showed minimal synergy. No antagonism was observed with any combination. Fosfomycin, ciprofloxacin and azlocillin in triple combination did not show synergy. The antimicrobial combinations tested against P. cepacia isolates from CF patients were indifferent. The combination of ciprofloxacin and fosfomycin may be clinically useful in selected P. aeruginosa pulmonary exacerbations in cystic fibrosis patients, particularly as an oral out-of-hospital treatment alternative or in cases where MICs for ciprofloxacin are elevated.
铜绿假单胞菌仍然是导致囊性纤维化（CF）患者发病和死亡的最常见呼吸道病原体。采用琼脂平板稀释棋盘法评估了环丙沙星和磷霉素（钙盐和 Tromethamine 盐）联合使用对来自 CF 患者的铜绿假单胞菌分离株的体外活性，这些患者均曾接受过环丙沙星治疗。所用药物浓度为通过口服和静脉注射（仅磷霉素）途径在患者体内可达到的浓度。考虑到静脉注射可达到的磷霉素浓度，发现对 60%的铜绿假单胞菌分离株有协同作用。口服给药后达到的浓度下，17%的分离株受到协同抑制。时间杀菌实验证实了这些结果。在存在磷霉素的情况下，环丙沙星对耐药铜绿假单胞菌的最低抑菌浓度（MIC）降至可达到的痰液和血清水平。然而，在渐进性耐药研究中，磷霉素未能延缓对环丙沙星耐药性的发展。还测试了氧氟沙星/磷霉素和环丙沙星/磷霉素的组合，但协同作用极小。任何组合均未观察到拮抗作用。环丙沙星、磷霉素和阿洛西林三联组合未显示协同作用。针对来自 CF 患者的洋葱伯克霍尔德菌分离株测试的抗菌组合无明显效果。环丙沙星和磷霉素的组合在囊性纤维化患者中选定的铜绿假单胞菌肺部加重感染中可能具有临床应用价值，特别是作为院外口服治疗选择或环丙沙星 MIC 升高的情况。
