title: Role of fosfomycin tromethamine in modulating non-specific defence mechanisms in chronic uremic patients towards ESBL-producing Escherichia coli.
abstract: Antimicrobial agents and polymorphonuclear cells (PMNs) have the potential to interact in such a way that improve the therapy for infectious diseases. In immunocompromised patients highly susceptible to microbial infections with high morbidity and mortality, several metabolic and functional alterations in PMNs, mostly related to microbicidal activity, are observed. Therefore, the antibiotic of choice should have a good antimicrobial effect without impairing host defences. The aim of this study is to evaluate in vitro effects of sub-inhibiting fosfomycin tromethamine (FT) concentrations on the primary functions of PMNs from healthy subjects and immunocompromised patients (haemodialysed and renal transplant recipients), against an ESBL-producing Escherichia coli, the most common aetiological agent in urinary tract infections (UTIs). FT is considered a first line drug in the eradication of UTIs due to its appropriate antimicrobial spectrum, oral bioavailability and minimal risk of microbial resistance. Our results provide evidence that FT is able to induce enhancement of the depressed phagocytic response of PMNs from patients on chronic haemodialysis and from renal transplant recipients, restoring their primary functions in vitro against ESBL-producing E. coli. All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT.
authors.affiliation: Department of Public Health and Microbiology, University of Turin, Turin, Italy. vivian.tullio@unito.it
authors.forename: V
authors.initials: V
authors.lastname: Tullio
authors.forename: A M
authors.initials: AM
authors.lastname: Cuffini
authors.forename: G
authors.initials: G
authors.lastname: Banche
authors.forename: N
authors.initials: N
authors.lastname: Mandras
authors.forename: V
authors.initials: V
authors.lastname: Allizond
authors.forename: J
authors.initials: J
authors.lastname: Roana
authors.forename: F
authors.initials: F
authors.lastname: Giacchino
authors.forename: F
authors.initials: F
authors.lastname: Bonello
authors.forename: D
authors.initials: D
authors.lastname: Ungheri
authors.forename: N A
authors.initials: NA
authors.lastname: Carlone
mesh_terms: D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001770:Blood Bactericidal Activity / Q000187:drug effects; D002908:Chronic Disease; D004926:Escherichia coli / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology; D004927:Escherichia coli Infections / Q000276:immunology*; D005260:Female; D005578:Fosfomycin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology; D014511:Uremia / Q000276:immunology*; D001618:beta-Lactamases / Q000096:biosynthesis*
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin; D001618:beta-Lactamases