Urinary Tract Conditions Affect Fosfomycin Activity against Escherichia coli Strains Harboring Chromosomal Mutations Involved in Fosfomycin Uptake

The steps by which strains harboring mutations related to fosfomycin (FOS) resistance arise and spread during urinary tract infections (UTIs) are far from being understood. The aim of this study was to evaluate the effects of urine, pH, and anaerobiosis on FOS activity against a set of isogenic stra...

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Bibliographic Details
Published in:	Antimicrobial agents and chemotherapy 2018-01, Vol.62 (1)
Main Authors:	Martín-Gutiérrez, G, Docobo-Pérez, F, Rodriguez-Beltrán, J, Rodríguez-Martínez, J M, Aznar, J, Pascual, A, Blázquez, J
Format:	Article
Language:	eng
Subjects:	Anti-Bacterial Agents Chromosomes, Bacterial Escherichia coli Escherichia coli Infections Fosfomycin Mechanisms of Resistance Urinary Tract Infections
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Summary:	The steps by which strains harboring mutations related to fosfomycin (FOS) resistance arise and spread during urinary tract infections (UTIs) are far from being understood. The aim of this study was to evaluate the effects of urine, pH, and anaerobiosis on FOS activity against a set of isogenic strains carrying the most prevalent chromosomal mutations conferring FOS resistance (Δ , Δ , Δ , and Δ ), either singly or in combination. We also studied fosfomycin-resistant clinical isolates from patients with UTI. Our results demonstrate that urinary tract physiological conditions might have a profound impact on FOS activity against strains with chromosomal FOS resistance mutations. Specifically, acidic pH values and anaerobiosis convert most of the strains categorized as resistant to fosfomycin according to the international guidelines to a susceptible status. Therefore, urinary pH values may have practical interest in the management of UTIs. Finally, our results, together with the high fitness cost associated with FOS resistance mutations, might explain the low prevalence of fosfomycin-resistant variants in UTIs.
ISSN:	0066-4804 1098-6596