title: Clinical significance of the pharmacokinetic and pharmacodynamic characteristics of fosfomycin for the treatment of patients with systemic infections.
abstract: The advancing antimicrobial drug resistance in common bacterial pathogens, along with the relative shortage of new antibacterial agents, call for the re-evaluation of available therapeutic options. Fosfomycin is an established treatment option for uncomplicated urinary tract infections. Here we review and evaluate the main pharmacokinetic and pharmacodynamic parameters of intravenously administered fosfomycin with regard to its use for systemic infections. Fosfomycin is a relatively small, hydrophilic agent with almost negligible serum protein binding. It is excreted unchanged in urine, achieving high concentrations for a prolonged period. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in sites such as serum, soft tissue, lungs, bone, cerebrospinal fluid and heart valves. Fosfomycin has shown antimicrobial activity against biofilms, particularly in combination with fluoroquinolones. It also exerts immunomodulatory effects, mainly on lymphocyte and neutrophil function. Potentially useful properties of fosfomycin regarding its use in combination regimens include reduction in the expression of certain penicillin-binding proteins and attenuation of nephrotoxicity caused by several antimicrobial agents. In conclusion, the pharmacokinetic and pharmacodynamic properties of fosfomycin do not preclude its use for various types of systemic infections and suggest further research on relevant clinical applications of this agent.
authors.affiliation: Alfa Institute of Biomedical Sciences (AIBS), Marousi, Athens, Greece.
authors.forename: Nikos
authors.initials: N
authors.lastname: Roussos
authors.forename: Drosos E
authors.initials: DE
authors.lastname: Karageorgopoulos
authors.forename: George
authors.initials: G
authors.lastname: Samonis
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Falagas
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy*; D005578:Fosfomycin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D006801:Humans; D007262:Infusions, Intravenous
chemical_list: D000900:Anti-Bacterial Agents; D005578:Fosfomycin