Levofloxacin and Ceftriaxone in Combination

21 Objectives: Whether synergistic antimicrobial combination in vitro would be beneficial in 22 down regulation of pneumococcal virulent genes and associated inflammation of the lung 23 tissue induced by multi-drug resistant S. pneumoniae infection in vivo needs to be elucidated 24 for considering this mode of therapy in case of severe pneumococcal infection. 25 Methods: We investigated the in vivo changes in expression of these virulence determinants 26 using an efficacious combination predetermined by in vitro studies. Balb/C mice were 27 infected with 10 6 CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone 28 at 50 mg/kg were initiated 18 h post infection; animals were sacrificed from 0 – 24 h after 29 initiation of treatment. Levels of cytokines, chemokines and CRP in serum and in lungs, 30 along with myeloperoxidase, nitric oxide, inflammatory cell count in broncho alveolar lavage 31 fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and iNOS 32 protein expression in lungs were estimated. 33 Results: Combination therapy down regulated inflammation and promoted bacterial 34 clearance. Pneumolysin and autolysin expression was down regulated with concomitant 35 decrease in expression of COX-2 and iNOS in lung tissue. 36 Conclusion: Thus this combination can be considered for therapeutic use even in cases of 37 pneumonia caused by drug resistant isolates. 38