title: Levofloxacin-ceftriaxone combination attenuates lung inflammation in a mouse model of bacteremic pneumonia caused by multidrug-resistant Streptococcus pneumoniae via inhibition of cytolytic activities of pneumolysin and autolysin.
abstract: In this study, our objective was to determine whether a synergistic antimicrobial combination in vitro would be beneficial in the downregulation of pneumococcal virulence genes and whether the associated inflammation of the lung tissue induced by multidrug-resistant Streptococcus pneumoniae infection in vivo needs to be elucidated in order to consider this mode of therapy in case of severe pneumococcal infection. We investigated in vivo changes in the expression of these virulence determinants using an efficacious combination determined in previous studies. BALB/c mice were infected with 10(6) CFU of bacteria. Intravenous levofloxacin at 150 mg/kg and/or ceftriaxone at 50 mg/kg were initiated 18 h postinfection; the animals were sacrificed 0 to 24 h after the initiation of treatment. The levels of cytokines, chemokines, and C-reactive protein (CRP) in the serum and lungs, along with the levels of myeloperoxidase and nitric oxide the inflammatory cell count in bronchoalveolar lavage fluid (BALF), changes in pneumolysin and autolysin gene expression and COX-2 and inducible nitric oxide synthase (iNOS) protein expression in the lungs were estimated. Combination therapy downregulated inflammation and promoted bacterial clearance. Pneumolysin and autolysin expression was downregulated, with a concomitant decrease in the expression of COX-2 and iNOS in lung tissue. Thus, the combination of levofloxacin and ceftriaxone can be considered for therapeutic use even in cases of pneumonia caused by drug-resistant isolates.
authors: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
authors: Arnab
authors: A
authors: Majhi
authors: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
authors: Rana
authors: R
authors: Adhikary
authors: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
authors: Aritra
authors: A
authors: Bhattacharyya
authors: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
authors: Sayantika
authors: S
authors: Mahanti
authors: Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India biswadevbishayi4@gmail.com.
authors: Biswadev
authors: B
authors: Bishayi
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016470:Bacteremia / Q000188:drug therapy / Q000378:metabolism / Q000382:microbiology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D001992:Bronchoalveolar Lavage Fluid / Q000382:microbiology; D002443:Ceftriaxone / Q000494:pharmacology*; D004195:Disease Models, Animal; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination / Q000379:methods; D064704:Levofloxacin / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000037:antagonists & inhibitors*; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011014:Pneumonia / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000378:metabolism / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000378:metabolism; D013301:Streptolysins / Q000037:antagonists & inhibitors*; D014774:Virulence / Q000187:drug effects; D037521:Virulence Factors / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D013301:Streptolysins; D037521:Virulence Factors; C032290:plY protein, Streptococcus pneumoniae; D064704:Levofloxacin; D002443:Ceftriaxone; D009238:N-Acetylmuramoyl-L-alanine Amidase