title: In vitro activity of fosfomycin against gram-negative urinary pathogens and the biological cost of fosfomycin resistance.
abstract: The aim of this study was to reassess the activity of fosfomycin against recently isolated uropathogens circulating in Italy and to evaluate the effect of fosfomycin resistance on the expression of several virulence traits using the rare mutant strains. In vitro activity of fosfomycin was evaluated using 441 Gram-negative organisms isolated from patients with uncomplicated urinary tract infections (UTIs). Fosfomycin was the most active antibiotic against Escherichia coli (99% susceptibility). The activity against Proteus mirabilis was more potent than that of co-trimoxazole and nitrofurantoin (87.5, 67 and 0% susceptibility, respectively). The other microorganisms, accounting for about 7% of all pathogens tested, showed variable susceptibilities to fosfomycin. Compared with susceptible strains, fosfomycin-resistant mutants showed a reduced rate of growth and were impaired in their ability to adhere to uroepithelial cells and to urinary catheters. They were also more resistant to UV irradiation and to phage T7 and showed diminished rates of colicin synthesis and transfer of plasmids.
authors.affiliation: Sezione di Microbiologia, Di.S.C.A.T., University of Genoa, Genoa, Italy. anna.marchese@unige.it
authors.forename: Anna
authors.initials: A
authors.lastname: Marchese
authors.forename: Laura
authors.initials: L
authors.lastname: Gualco
authors.forename: Eugenio A
authors.initials: EA
authors.lastname: Debbia
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Schito
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Schito
mesh_terms: D000332:Aerobiosis; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000502:physiology; D017123:Bacteriophage T7 / Q000472:pathogenicity; D001647:Bile Acids and Salts / Q000502:physiology; D002404:Catheterization; D002455:Cell Division / Q000502:physiology; D002478:Cells, Cultured; D003087:Colicins / Q000096:biosynthesis / Q000494:pharmacology; D024881:Drug Resistance, Bacterial / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology; D005578:Fosfomycin / Q000494:pharmacology*; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008826:Microbial Sensitivity Tests; D010957:Plasmids; D014466:Ultraviolet Rays; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology*; D014556:Urine / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D001647:Bile Acids and Salts; D003087:Colicins; D005578:Fosfomycin