Interaction of Staphylococcus aureus and Acinetobacter baumannii during In Vitro β-Lactam Exposure
| Autor: | Nicholas M. Smith, Katelyn Macias, Justin R. Lenhard, Sarah James, Jasleen Sidhu, Fanny Tan, Alexa Ang |
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| Rok vydání: | 2021 |
| Předmět: |
Pharmacology
0303 health sciences biology 030306 microbiology biochemical phenomena metabolism and nutrition Acinetobacter bacterial infections and mycoses biology.organism_classification Antimicrobial medicine.disease_cause Meropenem Acinetobacter baumannii Microbiology 03 medical and health sciences Infectious Diseases Pharmacokinetics Staphylococcus aureus Pharmacodynamics polycyclic compounds medicine bacteria Pharmacology (medical) Bacteria 030304 developmental biology medicine.drug |
| Zdroj: | Antimicrobial Agents and Chemotherapy. 65 |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.02414-20 |
| Popis: | We sought to determine if Acinetobacter baumannii is capable of altering the pharmacodynamics of an anti-staphylococcal β-lactam. Two strains of methicillin-susceptible Staphylococcus aureus (MSSA) and two A. baumannii isolates were studied in 24-h static time-killing experiments in monoculture or co-culture conditions. Bacterial killing of meropenem was described using an empiric pharmacokinetics/pharmacodynamics model that was developed using Hill functions. A mechanism-based pharmacodynamic model was also used to describe the effect of meropenem on each species of bacteria, inter-species interactions, and strain-based covariate effects. Monte Carlo simulations of bacterial killing effects were generated based on the population pharmacokinetics of meropenem in 2500 simulated critically ill subjects over 48h. Against one of the two MSSA isolates, the magnitude of bacterial killing (Edelta) decreased from -4.61 (95%CI -5.85 - -3.38) to -2.23 (95%CI -2.85 - -1.61) when cultured in the presence of carbapenem-resistant A. baumannii (CRAB). Similarly, the data were best described by a mechanism-based model where the number of A. baumannii cells produced a systematic increase in the S. aureus KC50 3.53-fold, thereby decreasing MSSA sensitivity to meropenem. A covariate effect by the CRAB resulted in a more pronounced increase in MSSA KC50 to meropenem (31.8-fold increase). However, Monte Carlo simulations demonstrated that a high intensity meropenem regimen is capable of sustained killing against both MSSA isolates despite the protection from A. baumannii Thus, A. baumannii and MSSA engage in complex interactions during β-lactam exposure, but optimal antimicrobial dosing is likely capable of killing MSSA despite potentially beneficial interplay with A. baumannii. |
| Databáze: | OpenAIRE |
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