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.

Atomic force microscopy study of the antibacterial effect of fosfomycin on methicillin-resistant Staphylococcus pseudintermedius

“…Fosfomycin has the ability to penetrate into the fluid of the interstitial space of soft tissues (Frossard et al 2000) to reach levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. The pharmacokinetic and pharmacodynamic properties of fosfomycin facilitate design of drug doses with clinically relevant concentrations for sites such as lungs, bone, soft tissue, and serum and heart valves (Roussos et al 2009 (Eaton et al 2008), kyotorphin peptide (Ribeiro et al 2012), carvacrol (Storia et al 2011) on Staphylococcal aureus biofilms. The nanoscale visualization and characterization of Staphylococcus aureus cells (Ribeiro et al 2012) demonstrated that kyotorphin perturbed the bacterial cell-wall membrane by blebbing, lysis and disruption.…”

Pharmacodynamic and pharmacokinetic considerations in the treatment of critically Ill patients infected with carbapenem-resistant Enterobacteriaceae

“…57,58 It is a small molecule that is highly distributed throughout body tissues. [59][60][61] It has negligible protein binding (»0%) and is cleared renally. Despite this route of elimination, limited information exists on the clearance of fosfomycin in renally-impaired patients; dosage adjustment of the intravenous formulation is recommended with a CrCl <50 mL/min.…”

“…62 As a small, hydrophilic molecule with low protein binding, fosfomycin is extensively removed during both intermittent and continuous hemodialysis. 60,61 The evidence-base for dosing in critically-ill patients is small, but available data indicate an increased volume of distribution that suggests a benefit of loading doses of intravenous fosfomycin. 60,61 Given orally, fosfomycin has a bioavailability of 30-40% and achieves very high concentrations in the urine in both renally sufficient patients and patients with mild renal insufficiency.…”

Successful treatment of lower urinary tract infections with oral fosfomycin: a report of three cases

“…Although fosfomycin tromethamine is only indicated for lower UTIs, it has been studied in both uncomplicated and complicated lower UTIs caused by MDR uropathogens because it shows synergistic action with other antimicrobial drugs (10) (11) . The parenteral formulation has been used in combination therapy to treat a wide range of infections including pneumonia and septicemia with cure rates >80% (12) . Given its low rates of resistance and the available evidence, fosfomycin may serve as a useful option for oral treatment of MDR uropathogens (1) .…”