title: Urinary Tract Physiological Conditions Promote Ciprofloxacin Resistance in Low-Level-Quinolone-Resistant Escherichia coli.
abstract: Escherichia coli isolates carrying chromosomally encoded low-level-quinolone-resistant (LLQR) determinants are frequently found in urinary tract infections (UTIs). LLQR mutations are considered the first step in the evolutionary pathway producing high-level fluoroquinolone resistance. Therefore, their evolution and dissemination might influence the outcome of fluoroquinolone treatments of UTI. Previous studies support the notion that low urine pH decreases susceptibility to ciprofloxacin (CIP) in E. coli However, the effect of the urinary tract physiological parameters on the activity of ciprofloxacin against LLQR E. coli strains has received little attention. We have studied the activity of ciprofloxacin under physiological urinary tract conditions against a set of well-characterized isogenic E. coli derivatives carrying the most prevalent chromosomal mutations (ΔmarR, gyrA-S83L, gyrA-D87N, and parC-S80R and some combinations). The results presented here demonstrate that all the LLQR strains studied became resistant to ciprofloxacin (according to CLSI guidelines) under physiological conditions whereas the control strain lacking LLQR mutations did not. Moreover, the survival of some LLQR E. coli variants increased up to 100-fold after challenge with a high concentration of ciprofloxacin under UTI conditions compared to the results seen with Mueller-Hinton broth. These selective conditions could explain the high prevalence of LLQR mutations in E. coli Furthermore, our data strongly suggest that recommended methods for MIC determination produce poor estimations of CIP activity against LLQR E. coli in UTIs.
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain Unidad Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain.
authors.forename: Guillermo
authors.identifier: 0000-0002-3456-9532
authors.initials: G
authors.lastname: Martín-Gutiérrez
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain.
authors.forename: Jerónimo
authors.identifier: 0000-0003-3014-1229
authors.initials: J
authors.lastname: Rodríguez-Beltrán
authors.affiliation: Departamento de Microbiología, Universidad de Sevilla, Seville, Spain.
authors.forename: José Manuel
authors.initials: JM
authors.lastname: Rodríguez-Martínez
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain.
authors.forename: Coloma
authors.initials: C
authors.lastname: Costas
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain Unidad Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Aznar
authors.affiliation: Departamento de Microbiología, Universidad de Sevilla, Seville, Spain Unidad Intercentros de Enfermedades Infecciosas, Microbiología y Medicina Preventiva, Hospitales Universitarios Virgen Macarena y Virgen del Rocío, Seville, Spain.
authors.forename: Álvaro
authors.initials: Á
authors.lastname: Pascual
authors.affiliation: Instituto de Biomedicina de Sevilla (IBIS), Hospital Universitario Virgen del Rocío, CSIC, Universidad de Sevilla, Seville, Spain Centro Nacional de Biotecnología (CNB), Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain blazquez@cnb.csic.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Blázquez
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002939:Ciprofloxacin / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000382:microbiology / Q000652:urine; D024841:Fluoroquinolones / Q000627:therapeutic use; D005838:Genotype; D064368:Healthy Volunteers; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics; D011446:Prospective Studies; D015363:Quinolones / Q000627:therapeutic use*; D014552:Urinary Tract Infections / Q000188:drug therapy* / Q000382:microbiology / Q000652:urine*
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D015363:Quinolones; D002939:Ciprofloxacin