In vitro activity of fosfomycin in combination with various antistaphylococcal substances

Using the chequerboard technique we studied the in vitro activity of the br oad spectrum antibiotic fosfomycin in combination with vancomycin, rifampic in, linezolid, quinupristin/dalfopristin, cefazolin, meropenem and moxiflox acin against two Staphylococcus epidermidis strains (ATCC 12228, DSM 3269) and five Staphylococcus aureus isolates (ATCC 29213, DSM 683, DSM 46320, GI SA 323/93, MRSA 3558/00). The phenomena of 'trailing' and 'skipped wells' d id not present a problem. Synergy was the most common effect of all drugs t ested in combination with fosfomycin; only combination with vancomycin show ed antagonism for two of seven isolates. Using a killing-curve technique fo sfomycin showed cidal activity, where increasing the drug concentration abo ve the MIC did not enhance killing velocity. Inhibitory concentrations of v ancomycin plus fosfomycin against DSM 46320 caused effects identical to tho se observed with vancomycin alone. The combination of fosfomycin plus linez olid exerted the bacteriostatic effect found with linezolid alone. Fosfomyc in plus quinupristin/dalfopristin exhibited the bactericidal effect found w ith fosfomycin alone (in contrast to the rapidly bactericidal effect of qui nupristin/dalfopristin). Electron microscopy showed that fosfomycin given i n combination with linezolid, quinupristin/dalfopristin or moxifloxacin (su bstances that do not cause morphological alterations when given alone) resu lted in 'cauliflower-shaped' distortion as caused by fosfomycin alone. Our in vitro data indicate considerable potential for fosfomycin used in combin ation with other antistaphylococcal antimicrobials, especially linezolid or quinupristin/dalfopristin.