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In vitro bactericidal activity of sulbactam plus ampicillin against methicillin-resistant Staphylococcus aureus
Abstract:
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.
Insights
Sulbactam/ampicillin demonstrated synergistic bactericidal activity against all tested Staphylococcus aureus strains, including penicillin-resistant and various methicillin-resistant groups. The combination showed significant killing in a simulated human blood model, though it was bacteriostatic against MR2 strains.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Staphylococcus aureus exhibits resistance to penicillin through penicillinase production.
- Methicillin resistance in S. aureus presents varying phenotypes (MR1, MR2) based on environmental conditions.
- Understanding antibiotic efficacy against resistant strains is crucial for effective treatment.
Purpose of the Study:
- To evaluate the in vitro bactericidal activity of sulbactam/ampicillin against different groups of Staphylococcus aureus.
- To determine the synergistic potential of sulbactam/ampicillin.
- To assess the combination's activity in a dynamic in vitro model simulating human pharmacokinetics.
Main Methods:
- Microtiter checkerboard method to assess synergy and fractional bactericidal index (FBI).
- Testing against three distinct groups of S. aureus: penicillin-resistant (PR), methicillin-resistant type 1 (MR1), and methicillin-resistant type 2 (MR2).
- In vitro kinetic model simulating human blood antibiotic levels after intravenous administration.
Main Results:
- Sulbactam/ampicillin exhibited synergistic bactericidal activity against all tested S. aureus strains (FBI ≤ 0.10).
- A linear relationship was observed between antibiotic concentrations and bactericidal activity within each strain group.
- The combination achieved ~99% killing in the kinetic model, except for MR2 strains where it was bacteriostatic.
Conclusions:
- Sulbactam/ampicillin is a synergistic combination with potent in vitro bactericidal activity against penicillin-resistant and methicillin-susceptible S. aureus.
- The combination demonstrates promising efficacy in a simulated pharmacokinetic model.
- Activity against certain methicillin-resistant strains (MR2) may be limited to bacteriostasis, warranting further investigation.