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Oral Fosfomycin Efficacy with Variable Urinary Exposures following Single and Multiple Doses against <i>Enterobacterales</i> : the Importance of Heteroresistance for Growth Outcome

Iain J. Abbott, Elke van Gorp, Rixt A. Wijma, Joseph Meletiadis, Jason A. Roberts, Johan W. Mouton, Anton Y. Peleg

2020Antimicrobial Agents and Chemotherapy19 citationsDOIOpen Access PDF

Abstract

, 0.99), with a bias of 3.8% ± 5.7%. All 5/5 isolates with MICs of ≤1 μg/ml had no HLR and were killed, whereas 8/11 isolates with higher MICs regrew regardless of exposure to high or low urinary concentrations. A disk diffusion zone of <24 mm was a better predictor for baseline HLR and regrowth. Administering 3 doses with average exposures provided very limited additional kill. These results suggest that baseline heteroresistance is important for treatment response, while increased drug exposure and administering multiple doses may not be better than standard single-dose fosfomycin therapy.

Topics & Concepts

FosfomycinUrinary systemMedicineAntimicrobialPharmacologyInternal medicineBiologyMicrobiologyUrinary Tract Infections ManagementPediatric Urology and Nephrology StudiesUrinary Bladder and Prostate Research