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Potency of Meropenem-Vaborbactam in Lung Surfactant
Debora Rubio-Aparicio1, Jeff Loutit1, Michael Dudley1
1The Medicines Company, San Diego, CA.
Abstract:
This study investigated whether pulmonary surfactant has an effect on the in vitro antibacterial activity of either meropenem alone or meropenem in combination with vaborbactam at a fixed concentration of 8 μg/ml against several Klebsiella pneumoniae carbapenemase (KPC)-producing strains of Gram-negative bacteria. Results showed that the potency of meropenem alone and that of meropenem-vaborbactam were not affected when tested with pulmonary surfactant.
Insights
Pulmonary surfactant did not impact the effectiveness of meropenem or meropenem-vaborbactam against carbapenemase-producing bacteria. This finding is crucial for understanding antibiotic efficacy in lung infections.
Area of Science:
- Antimicrobial resistance
- Pharmacology
- Infectious diseases
Background:
- Carbapenemase-producing Gram-negative bacteria, particularly Klebsiella pneumoniae carbapenemase (KPC)-producing strains, pose a significant threat due to limited treatment options.
- Meropenem is a carbapenem antibiotic, and vaborbactam is a novel beta-lactamase inhibitor, often used in combination to combat resistant bacteria.
- Pulmonary surfactant is a complex mixture of lipids and proteins lining the alveoli, potentially interacting with antimicrobial agents in the lung environment.
Purpose of the Study:
- To determine if pulmonary surfactant affects the in vitro antibacterial activity of meropenem.
- To evaluate the impact of pulmonary surfactant on the in vitro antibacterial activity of meropenem in combination with vaborbactam.
- To assess the efficacy of meropenem and meropenem-vaborbactam against Klebsiella pneumoniae carbapenemase (KPC)-producing Gram-negative bacteria in the presence of pulmonary surfactant.
Main Methods:
- In vitro susceptibility testing was performed.
- Meropenem alone and meropenem-vaborbactam combination were tested at a fixed concentration of 8 μg/ml.
- The antibacterial activity was assessed against several KPC-producing Gram-negative bacterial strains in the presence and absence of pulmonary surfactant.
Main Results:
- The antibacterial potency of meropenem alone was not altered by the presence of pulmonary surfactant.
- The antibacterial potency of the meropenem-vaborbactam combination was not affected by pulmonary surfactant.
- Pulmonary surfactant did not influence the efficacy of either meropenem or meropenem-vaborbactam against the tested KPC-producing strains.
Conclusions:
- Pulmonary surfactant does not appear to inhibit the in vitro antibacterial activity of meropenem or meropenem-vaborbactam.
- These findings suggest that meropenem and meropenem-vaborbactam may retain their efficacy when administered in the context of lung infections where pulmonary surfactant is present.
- Further in vivo studies are warranted to confirm these in vitro results and assess the clinical implications for treating Gram-negative bacterial pneumonia.