In Vitro Bactericidal Activity of Sulbactam plus Ampicillin Against Methicillin-Resistant Staphylococcus aureus

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Abstract
By a microtiter checkerboard method, the in vitro bactericidal activity of sulbactam/ampicillin wastested against three groups of Staphylococcus aureus strains: (1) group PR (penicillin-resistant through the production of penicillinase; methicillin-susceptible both at 30°C in medium containing 5% NaCI and at 35°C in medium without NaCI; n = 10); (2) group MRI (methicillin-resistant under the former conditions but not under the latter; n = 15); and (3) group MR2 (methicillin-resistant under both sets of conditions; n = 20). Sulbactam/ampicillin was synergistic against all strains (fractional bactericidal index, ⩽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 ATCC6538 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 ∼99% except with the MR2 strains, against which the combination was bacteriostatic.

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