Inhibition of Daptomycin by Pulmonary Surfactant: In Vitro Modeling and Clinical Impact

The lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. Daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy...

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Bibliographic Details
Published in:The Journal of infectious diseases 2005-06, Vol.191 (12), p.2149-2152
Main Authors: Silverman, Jared A., Mortin, Lawrence I., VanPraagh, Andrew D. G., Li, Tongchuan, Alder, Jeff
Format: Article
Language:English
Subjects:
Animal models
Animals
Anti-Bacterial Agents - metabolism
Anti-Bacterial Agents - pharmacology
Antibiotics
Cell aggregates
Daptomycin - antagonists & inhibitors
Daptomycin - metabolism
Daptomycin - pharmacology
Drug Resistance, Bacterial
Infections
Lipids
Lung - physiology
Lungs
Mice
Microbial Sensitivity Tests
Pathogenes and Host Response
Pneumococcal Infections - drug therapy
Pneumonia
Pneumonia, Bacterial - drug therapy
Pneumonia, Bacterial - metabolism
Pulmonary surfactants
Pulmonary Surfactants - metabolism
Pulmonary Surfactants - pharmacology
Rats
Staphylococcal Infections - drug therapy
Staphylococcus aureus
Streptococcus pneumoniae
Surfactants
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Summary:The lipopeptide daptomycin has been approved for use in skin and skin-structure infections but has failed to meet statistical noninferiority criteria in a clinical trial for severe community-acquired pneumonia. Daptomycin exhibited an unusual pattern of activity in pulmonary animal models: efficacy in Staphylococcus aureus hematogenous pneumonia and inhalation anthrax but no activity against Streptococcus pneumoniae in simple bronchial-alveolar pneumonia. Daptomycin was shown to interact in vitro with pulmonary surfactant, resulting in inhibition of antibacterial activity. This effect was specific to daptomycin and consistent with its known mechanism of action. This represents the first example of organ-specific inhibition of an antibiotic.
ISSN:0022-1899
1537-6613
DOI:10.1086/430352