EFFECTIVE TREATMENT OF CEPHALOSPORIN-RIFAMPIN COMBINATIONS AGAINST CRYPTIC METHICILLIN-RESISTANT BETA-LACTAMASE-PRODUCING COAGULASE-NEGATIVE STAPHYLOCOCCAL EXPERIMENTAL ENDOCARDITIS

The efficacy of cefazolin or cefpirome alone or combined with rifampin was compared with that of vancomycin alone or combined with rifampin in an experimental model of methicillin-resistant, beta-lactamase-prod ucing, coagulase-negative staphylococcal endocarditis. Phenotypically, the mecA gene-positive strain used in vivo did not exhibit methicilli n resistance by the agar dilution or disk susceptibility method but wa s resistant in vitro (oxacillin MIC, 64 mu g/ml) by the microtiter dil ution method with 2% NaCl supplementation. Macrodilution broth suscept ibilities at standard inocula failed to demonstrate cross-resistance o f staphylococci to cefazolin (MIC, 8 mu g/ml) or cefpirome (MIC, 4 mu g/ml). In vivo, vancomycin and cefpirome had similar activities, and b oth regimens were more effective than was cefazolin alone. While the M IC of rifampin was low (0.031 mu g/ml), monotherapy with rifampin resu lted in a bimodal distribution of outcomes due to the expected emergen ce of resistant mutants. The results in vitro of time-kill synergy stu dies using rifampin in combination with cefazolin or cefpirome varied with the antimicrobial concentrations tested and did not reliably pred ict activities in vivo of rifampin-beta-lactam combination therapies. Cefpirome, but not cefazolin or vancomycin, in combination with rifamp in was synergistic in vivo. Cefpirome in combination with rifampin was more effective than was cefazolin in combination with rifampin. Both cephalosporin-rifampin regimens were significantly more effective than was cephalosporin or vancomycin monotherapy and were as effective as vancomycin combined with rifampin. These data support further evaluati on of rifampin-beta-lactam combinations as possible alternative therap ies to vancomycin-containing regimens for selected methicillin-resista nt coagulase-negative staphylococcal infections.