Distribution and Antimicrobial Activity of Fosfomycin in the Interstitial Fluid of Human Soft Tissues

Abstract

Fosfomycin is a broad-spectrum antibiotic which is established as therapy for uncomplicated lower urinary tract infections. In addition, preliminary data indicate that fosfomycin has a potential role in the treatment of soft tissue infections. However, the use of fosfomycin has not been established for this condition, and it is unclear whether the level of fosfomycin penetration into human soft tissues is high enough to eradicate relevant pathogens. To better characterize the antibiotic potential of fosfomycin, we applied a combined in vivo pharmacokinetic-in vitro pharmacodynamic model to human volunteers. In corresponding in vitro simulation experiments with selected isolates of Staphylococcus aureus, Enterobacter cloacae, and Serratia marcescens for which MICs were 16 g/ml, organisms were undetectable after a single dosing interval. Fosfomycin exhibits a strong ability to penetrate into the fluid of the interstitial space of soft tissues and reaches levels sufficient to substantially inhibit the growth of relevant bacteria at the target site. We therefore conclude that fosfomycin might qualify as an alternative candidate for the therapy of soft tissue infections.

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

“…administration of 4 g and 8 g of fosfomycin to healthy volunteers resulted in muscle and subcutaneous tissue fosfomycin AUC 0-8h values that were ca. 50% and 70%, respectively, of the corresponding serum values [28]. Similar findings have been observed A c c e p t e d M a n u s c r i p t in additional studies evaluating the degree of penetration of fosfomycin into soft tissue in patients with sepsis, cellulitis or diabetic foot infections [30,31,60].…”

“…Several studies have evaluated the degree of penetration of fosfomycin into soft tissue (muscle or subcutaneous tissue) [28,30,31,60]. Briefly, i.v.…”

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

“…Fosfomycin exert antimicrobial activity by inhibiting UDP-N-acetylglucosamine enolpyruvyl transferase enzyme (Eschenburg et al 2005) that catalysis the first step in bacterial cell-wall synthesis within the cell. 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.…”

In vitro activity of minocycline combined with fosfomycin against clinical isolates of methicillin-resistant Staphylococcus aureus

“…Both agents have shown good penetration to both the above sites of infection. [22][23][24] Combination antimicrobial therapy can be of value for the treatment of various types of infections. Synergy is one of the most common reasons for using combination antimicrobial therapy.…”