title: Treatment with protein synthesis inhibitors improves outcomes of secondary bacterial pneumonia after influenza.
abstract: 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 beta-lactam therapy may not be optimal as a first-line treatment for community-acquired pneumonia when it follows influenza.
authors.affiliation: Department of Infectious Diseases and the Veterinary Pathology Core, St. Jude Children's Research Hospital, Memphis, Tennessee 38105-2794, USA.
authors.forename: Asa
authors.initials: A
authors.lastname: Karlström
authors.forename: Kelli L
authors.initials: KL
authors.lastname: Boyd
authors.forename: B Keith
authors.initials: BK
authors.lastname: English
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: McCullers
mesh_terms: D000667:Ampicillin / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002981:Clindamycin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D004359:Drug Therapy, Combination; D005260:Female; D007249:Inflammation / Q000378:metabolism / Q000517:prevention & control; D009980:Influenza A virus / Q000187:drug effects; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000187:drug effects; D009976:Orthomyxoviridae Infections / Q000150:complications*; D011018:Pneumonia, Pneumococcal / Q000150:complications / Q000188:drug therapy*; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D011500:Protein Synthesis Inhibitors; D014409:Tumor Necrosis Factor-alpha; D002981:Clindamycin; D000667:Ampicillin; C119964:LytB protein, Streptococcus; D009238:N-Acetylmuramoyl-L-alanine Amidase