Evaluation of Immunocompetent Urinary Tract Infected Balb/C Mouse Model For the Study of Antibiotic Resistance Development Using <i>Escherichia Coli</i> CFT073 Infection
Ashok Chockalingam,
Sharron Stewart,
Lin Xu,
Adarsh Gandhi,
Murali K. Matta,
Vikram Patel,
Leonard Sacks,
Rodney Rouse
Affiliations
Ashok Chockalingam
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Sharron Stewart
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Lin Xu
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Adarsh Gandhi
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Murali K. Matta
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Vikram Patel
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Leonard Sacks
Office of Medical Policy; U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Rodney Rouse
Office of Translational Science, Office of Clinical Pharmacology, Division of Applied Regulatory Science U.S. Food and Drug Administration, Center for Drug Evaluation and Research, White Oak Federal Research Center, Silver Spring, MD 20993, USA
Urinary tract infections (UTI) are common worldwide and are becoming increasingly difficult to treat because of the development of antibiotic resistance. Immunocompetent murine models of human UTI have been used to study pathogenesis and treatment but not for investigating resistance development after treatment with antibiotics. In this study, intravesical inoculation of uropathogenic Escherichia coli CFT073 in immunocompetent Balb/c mice was used as a model of human UTI. The value of the model in investigating antibiotic exposure on in vivo emergence of antibiotic resistance was examined. Experimentally infected mice were treated with 20 or 200 mg/kg ampicillin, 5 or 50 mg/kg ciprofloxacin, or 100 or 1000 mg/kg of fosfomycin. Ampicillin and ciprofloxacin were given twice daily at 8 h intervals, and fosfomycin was given once daily. Antibiotic treatment began 24 h after bacterial inoculation and ended after 72 h following the initial treatment. Although minimum inhibitory concentrations (MIC) for the experimental strain of E. coli were exceeded at peak concentrations in tissues and consistently in urine, low levels of bacteria persisted in tissues in all experiments. E. coli from bladder tissue, kidney, and urine grew on plates containing 1× MIC of antibiotic, but none grew at 3× MIC. This model is not suitable for studying emergent resistance but might serve to examine bacterial persistence.
