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
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