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. coll All these data permit the conclusion that uremic-infected patients might additionally benefit from the immunomodulating properties of FT.

Susceptibility of Urinary Tract Bacteria to Fosfomycin

“…There is some evidence that fosfomycin might be a promising solution for the treatment of such infections (19,20,30). It is also suggested that the antimicrobial activity of fosfomycin against ESBL-producing E. coli may be accompanied by an immunomodulating activity (37). Notably, in our study, fosfomycin was active against all the ESBL-producing E. coli and K. pneumoniae isolates.…”

Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections

“…The latter effect of fosfomycin has been demonstrated on neutrophils derived from immunocompromised patients [92,93].…”

Fosfomycin

“…Fosfomycin also exhibits an immunomodulatory effect on B-cell activation (22). Fosfomycin enhances neutrophil phagocytic killing of invading pathogens (23), even in patients on chronic hemodialysis and renal transplantation (24). Fosfomycin resulted in enhanced bactericidal ability of neutrophils compared to other antimicrobials (25).…”