Antimicrob Agents Chemother. 2014 Jun 23. pii: AAC.03245-14. [Epub ahead of print]
LEVOFLOXACIN AND CEFTRIAXONE IN COMBINATION ATTENUATES LUNG INFLAMMATION IN A MOUSE MODEL OF BACTEREMIC PNEUMONIA BY MULTI-DRUG RESISTANT Streptococcus pneumoniae VIA INHIBITION OF CYTOLYTIC ACTIVITIES OF PNEUMOLYSIN AND AUTOLYSIN.
Majhi A1, Adhikary R1, Bhattacharyya A1, Mahanti S1, Bishayi B2.
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Abstract
OBJECTIVES:
Whether synergistic antimicrobial combination in vitro would be beneficial in down regulation of pneumococcal virulent genes and associated inflammation of the lung tissue induced by multi-drug resistant S. pneumoniae infection in vivo needs to be elucidated for considering this mode of therapy in case of severe pneumococcal infection.
METHODS:
We investigated the in vivo changes in expression of these virulence determinants using an efficacious combination predetermined by in vitro studies. Balb/C mice were infected with 106 CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h post infection; animals were sacrificed from 0 - 24 h after initiation of treatment. Levels of cytokines, chemokines and CRP in serum and in lungs, along with myeloperoxidase, nitric oxide, inflammatory cell count in broncho alveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and iNOS protein expression in lungs were estimated.
RESULTS:
Combination therapy down regulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was down regulated with concomitant decrease in expression of COX-2 and iNOS in lung tissue.
CONCLUSION:
Thus this combination can be considered for therapeutic use even in cases of pneumonia caused by drug resistant isolates.
Copyright © 2014, American Society for Microbiology. All Rights Reserved.
PMID: 24957840 [PubMed - as supplied by publisher]
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