Evaluation of a Sequential Antibiotic Treatment Regimen of Ampicillin, Ciprofloxacin and Fosfomycin against Escherichia coli CFT073 in the Hollow Fiber Infection Model Compared with Simultaneous Combination Treatment

被引:2
作者
Krishna, Ashok [1 ]
Zere, Tesfalem [2 ]
Mistry, Sabyasachy [1 ]
Ismaiel, Omnia [1 ]
Stone, Heather [3 ]
Sacks, Leonard V. [3 ]
Weaver, James L. [1 ]
机构
[1] US FDA, Ctr Drug Evaluat & Res, Div Appl Regulatory Sci, Off Clin Pharmacol, Silver Spring, MD 20993 USA
[2] US FDA, Ctr Devices & Radiol Hlth, Off Prod Evaluat & Qual, Silver Spring, MD 20993 USA
[3] US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Silver Spring, MD 20993 USA
来源
ANTIBIOTICS-BASEL | 2022年 / 11卷 / 12期
关键词
antibiotics; antibiotic resistance; hollow fiber infection model; sequential antibiotic regimen; E; coli CFT073; ANTIMICROBIAL RESISTANCE; PHARMACODYNAMICS; EVOLUTION; THERAPY;
D O I
10.3390/antibiotics11121705
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Objective: Employ the hollow fiber infection model (HFIM) to study sequential antibiotic administration (ampicillin, ciprofloxacin and fosfomycin) using human pharmacokinetic profiles to measure changes in the rate of antibiotic resistance development and compare this to simultaneous combination therapy with the same antibiotic combinations. Methods: Escherichia coli CFT073, a clinical uropathogenic strain, was exposed individually to clinically relevant pharmacokinetic concentrations of ampicillin on day 1, ciprofloxacin on day 2 and fosfomycin on day 3. This sequence was continued for 10 days in the HFIM. Bacterial samples were collected at different time points to enumerate total and resistant bacterial populations. The results were compared with the simultaneous combination therapy previously studied. Results: Sequential antibiotic treatment (ampicillin-ciprofloxacin-fosfomycin sequence) resulted in the early emergence of single and multi-antibiotic-resistant subpopulations, while the simultaneous treatment regimen significantly delayed or prevented the emergence of resistant subpopulations. Conclusion: Sequential administration of these antibiotic monotherapies did not significantly delay the emergence of resistant subpopulations compared to simultaneous treatment with combinations of the same antibiotics. Further studies are warranted to evaluate different sequences of the same antibiotics in delaying emergent resistance.
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页数:11
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