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Effect of ampicillin/sulbactam on human polymorphonuclear leukocyte function
A Pascual1, M C Conejo, G López Lopez
1Department of Microbiology, School of Medicine, University Hospital, Sevilla, Spain.
Abstract:
The effect of ampicillin and sulbactam on the interaction in vitro of human polymorphonuclear leukocytes (PMN) with Staphylococcus aureus was examined. The exposure of a non-penicillinase-producing S. aureus strain to one fourth the MIC of ampicillin but not of sulbactam significantly increased the uptake of bacteria by human PMN. This effect was also observed when bacteria were exposed to the MIC0.25 of different combinations of ampicillin and sulbactam (2/1, 1/1, 1/4, 1/8 and 1/32). These effects were not observed when a penicillinase-producing strain was used. The production of superoxide and hydrogen peroxide radicals by human PMN was not affected by the presence of these antimicrobials. Ampicillin and sulbactam, neither alone nor in combination, showed intracellular activity against S. aureus within human PMN.
Insights
Ampicillin enhances Staphylococcus aureus uptake by human immune cells (PMN), but only for non-penicillinase-producing strains. This effect was not seen with penicillinase-producing strains or intracellularly.
Area of Science:
- Immunology
- Microbiology
- Pharmacology
Background:
- Human polymorphonuclear leukocytes (PMN) are crucial for combating bacterial infections, particularly Staphylococcus aureus.
- The efficacy of antibiotics like ampicillin and sulbactam can be influenced by bacterial resistance mechanisms and host immune cell interactions.
- Understanding how antimicrobial agents affect the interplay between bacteria and immune cells is vital for optimizing treatment strategies.
Purpose of the Study:
- To investigate the in vitro effects of ampicillin and sulbactam on the interaction between human PMN and Staphylococcus aureus.
- To determine if these antimicrobials influence bacterial uptake by PMN.
- To assess the impact on reactive oxygen species production and intracellular bacterial killing.
Main Methods:
- Exposure of non-penicillinase-producing and penicillinase-producing Staphylococcus aureus strains to sub-inhibitory concentrations of ampicillin and sulbactam.
- Co-incubation of treated bacteria with human polymorphonuclear leukocytes (PMN).
- Quantification of bacterial uptake by PMN.
- Measurement of superoxide and hydrogen peroxide radical production by PMN.
- Assessment of intracellular bacterial killing.
Main Results:
- Exposure to ampicillin (at 1/4 MIC) significantly increased the uptake of non-penicillinase-producing S. aureus by human PMN.
- Sulbactam alone did not enhance bacterial uptake.
- Combinations of ampicillin and sulbactam also increased uptake of the non-penicillinase-producing strain.
- No enhancement of bacterial uptake was observed with penicillinase-producing S. aureus strains.
- Neither ampicillin nor sulbactam affected PMN production of superoxide or hydrogen peroxide radicals.
- No intracellular activity against S. aureus within human PMN was demonstrated for either agent alone or in combination.
Conclusions:
- Ampicillin, at sub-inhibitory concentrations, can enhance the phagocytic activity of human PMN against non-penicillinase-producing Staphylococcus aureus.
- This effect is strain-dependent and does not extend to penicillinase-producing strains.
- Ampicillin and sulbactam do not directly impact PMN's oxidative burst or demonstrate intracellular bactericidal activity in this model.