In vitro bactericidal activity of sulbactam plus ampicillin against methicillin-resistant Staphylococcus aureus.

By a microtiter checkerboard method, the in vitro bactericidal activity of sulbactam/ampicillin was tested against three groups of Staphylococcus aureus strains: group PR (penicillin-resistant through the production of penicillinase; methicillin-susceptible both at 30 degrees C in medium containing 5% NaCl and at 35 degrees C in medium without NaCl; n = 10); group MR1 (methicillin-resistant under the former conditions but not under the latter; n = 15); and group MR2 (methicillin-resistant under both sets of conditions; n = 20). Sulbactam/ampicillin was synergistic against all strains (fractional bactericidal index, less than or equal to 0.10). Moreover, there was a linear relation in each group between the different concentrations of the two antibiotics required for bactericidal activity. Thus, an equation of bactericidal synergy could be formulated for the combination. The bactericidal activity of sulbactam/ampicillin was assessed against one strain of each group and against a reference strain (S. aureus ATCC 6538 P) in an in vitro model simulating the kinetics of both antibiotics in human blood after intravenous administration of 2 g of ampicillin and 1 g of sulbactam. The observed rate of killing was approximately 99% except with the MR2 strains, against which the combination was bacteriostatic.