In vitro activity of fosfomycin, alone and in combination, against methicillin-resistant Staphylococcus aureus

Abstract

We tested 148 strains of clinical isolates of methicillin-resistant Staphylococcus aureus against fosfomycin alone and in combination with methicillin, cefamandole, gentamicin, trimethoprim, and vancomycin. Fosfomycin inhibited 90% of the 148 methicillin-resistant S. aureus strains at a concentration of 4 ,ug/ml. Synergism was observed in 97 strains (66%) with fosfomycin-cefamandole and in 69 strains (46%) with fosfomycin-methicillin. The combinations of fosfomycin with vancomycin, gentamicin, and trimethoprim were indifferent in most strains.

A Randomized Double-Blind Placebo-Controlled Dose-Escalation Phase 1 Study of Aerosolized Amikacin and Fosfomycin Delivered via the PARI Investigational eFlow® Inline Nebulizer System in Mechanically Ventilated Patients

“…(15,23) However, for highly fosfomycin-resistant strains, levels would not exceed the MIC for more than 6-8 hr over a 24-hr period, even with BID dosing. The peak amikacin tracheal concentrations achieved with the 300/120 mg dose of amikacin/fosfomycin were higher than what was reported with a 400-mg dose of amikacin sulfate using the breath-actuated vibrating plate nebulizing system.…”

“…(10) In addition, fosfomycin has bactericidal activity against methicillin-resistant Staphylococcus aureus at low MICs. (15) As measured by laser diffractometry (Mastersizer X, Malvern, UK), the average mass median diameter (MMD) of the amikacin/fosfomycin (5:2) solution increased from 2.9 to 3.3 lm after humidification (personal communication, PARI Pharma). The pH of the formulation was corrected with HCl, which was chosen to provide a permeable anion to the antibiotic mixture, the absence of which is known to induce cough.…”

In vitro interactions between different beta-lactam antibiotics and fosfomycin against bloodstream isolates of enterococci

“…It acts against gram-positive and gram-negative bacteria by inhibiting the first step in bacterial cell wall synthesis (4,12). Synergistic bacteriostatic and bactericidal (where tested) effects between different ␤-lactams and fosfomycin have previously been described to occur in vitro against different genera of gram-positive cocci, including staphylococci (1,7,9,16,18), pneumococci (3,6), and enterococci (7,9). Against enterococci, oxacillin (9), cefotaxime (9), and imipenem (7) have been until now the only ␤-lactams tested in combination with fosfomycin.…”

Efficacy of pefloxacin-fosfomycin in experimental endocarditis caused by methicillin-resistant Staphylococcus aureus

“…Although pefloxacin has been effective in some experimental MRSA infections (19,22), the emergence of resistance to pefloxacin among staphylococci has been noted both in vitro (3) and in vivo (27). Emergence of resistant colonies also limits the utility of other antistaphylococcal antimicrobial agents, including fosfomycin, a relatively nontoxic drug which inhibits an early step in peptidoglycan synthesis (1,10,14). Because antimicrobial combinations may suppress the emergence of drug-resistant populations and/or achieve inhibitory or bactericidal synergism, we investigated the efficacy of the pefloxacin-fosfomycin combination and of either drug alone in a rat model of endocarditis due to MRSA.…”