Treatment with Protein Synthesis Inhibitors Improves Outcomes of Secondary Bacterial Pneumonia after Influenza

Pneumonia occurring as a secondary infection after influenza is a major cause of excess morbidity and mortality, despite the availability and use of antibiotics active against Streptococcus pneumoniae.We hypothesized that the use of a bacteriostatic protein synthesis inhibitor would improve outcomes...

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Bibliographic Details
Published in:The Journal of infectious diseases 2009-02, Vol.199 (3), p.311-319
Main Authors: Karlström, Åsa, Boyd, Kelli, English, B. Keith, McCullers, Jonathan A.
Format: Article
Language:English
Subjects:
Ampicillin - pharmacology
Ampicillin - therapeutic use
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Bacteria
Bacterial pneumonia
Biological and medical sciences
Bronchoalveolar Lavage Fluid - cytology
Clindamycin - pharmacology
Clindamycin - therapeutic use
Cytokines
Disease Models, Animal
Dosage
Drug Screening Assays, Antitumor
Drug Therapy, Combination
Female
Fundamental and applied biological sciences. Psychology
Infectious diseases
Inflammation - metabolism
Inflammation - prevention & control
Influenza A virus - drug effects
Lung - metabolism
Lung - pathology
Lungs
Medical sciences
Mice
Mice, Inbred BALB C
Microbiology
Mortality
N-Acetylmuramoyl-L-alanine Amidase - drug effects
Orthomyxoviridae
Orthomyxoviridae Infections - complications
Pneumococcal pneumonia
Pneumonia, Pneumococcal - complications
Pneumonia, Pneumococcal - drug therapy
Protein Synthesis Inhibitors - pharmacology
Protein Synthesis Inhibitors - therapeutic use
Tumor Necrosis Factor-alpha - metabolism
Viral pneumonia
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Summary:Pneumonia occurring as a secondary infection after influenza is a major cause of excess morbidity and mortality, despite the availability and use of antibiotics active against Streptococcus pneumoniae.We hypothesized that the use of a bacteriostatic protein synthesis inhibitor would improve outcomes by reducing the inflammatory response. BALB/cJ mice infected with influenza virus and superinfected with S. pneumoniae were treated with either the cell-wall-active antibiotic ampicillin or the protein synthesis inhibitor clindamycin or azithromycin. In the model, ampicillin therapy performed significantly worse (survival rate, 56%) than (1) clindamycin therapy used either alone (82%) or in combination with ampicillin (80%) and (2) azithromycin (92%). Improved survival appeared to be mediated by decreased inflammation manifested as lower levels of inflammatory cells and proinflammatory cytokines in the lungs and by observation of less-severe histopathologic findings. These data suggest that β-lactam therapy may not be optimal as a first-line treatment for community-acquired pneumonia when it follows influenza.
ISSN:0022-1899
1537-6613
DOI:10.1086/596051