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Abstract
Although a marked decrease in mortality associated with bacterial infections is attributed to the discovery of antibiotics, antibiotic resistance has become a global health concern due to their misuse. A dynamic in vitro hollow-fiber system was used to study antibiotic resistance in Escherichia coli using ampicillin. An LC–MS/MS assay was validated for quantitative analysis of ampicillin in Luria–Bertani broth. The assay was linear from 0.10–50.00 μg/ml. The assay met acceptance criteria for inter- and intra-assay precisions and accuracies across three quality controls. Stability of ampicillin was confirmed at three different storage conditions. In vitro data were similar to simulated plasma PK data further confirming the appropriateness of the experimental design to quantify antibiotics and study occurrence of antimicrobial resistance in real-time.
Lay abstract Urinary tract infections are becoming untreatable with the rise of antibiotic resistance. Escherichia coli is the cause of most urinary tract infections, one of the most common infections that require treatment with antibiotics. The utility of a hollow-fiber system, which is a dynamic system mimicking human disposition of antibiotics more closely than static systems, can help design single or combination drug dosing regimens for antibiotics based on their pharmacokinetic profiles. The data generated from these studies can be utilized to help understand the time when bacteria start developing resistance and aid in adjusting the drug combinations and their doses.
Financial & competing interests disclosure
The authors would like to thank the Center for Drugs Evaluation and Research for funding this study. All the work presented in this manuscript was supported by intramural grants from the FDA. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.
Author contributions
A Gandhi conducted analytical experiments, performed data analysis and contributed to the writing of the manuscript. M Matta contributed to the writing of the manuscript. T Zere conducted hollow-fiber experiments. J Weaver designed experiments, contributed to the writing of the manuscript and secured funds.