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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.
Majhi, Arnab; Adhikary, Rana; Bhattacharyya, Aritra; Mahanti, Sayantika; Bishayi, Biswadev.
Afiliación
  • Majhi A; Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
  • Adhikary R; Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
  • Bhattacharyya A; Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
  • Mahanti S; Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India.
  • Bishayi B; Department of Physiology, Immunology Laboratory, University of Calcutta, University Colleges of Science and Technology, Calcutta, West Bengal, India biswadevbishayi4@gmail.com.
Antimicrob Agents Chemother ; 58(9): 5164-80, 2014 Sep.
Article en En | MEDLINE | ID: mdl-24957840
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Neumocócicas / Neumonía / Neumonía Neumocócica / Streptococcus pneumoniae / Estreptolisinas / Ceftriaxona / Levofloxacino / N-Acetil Muramoil-L-Alanina Amidasa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Antimicrob Agents Chemother Año: 2014 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Infecciones Neumocócicas / Neumonía / Neumonía Neumocócica / Streptococcus pneumoniae / Estreptolisinas / Ceftriaxona / Levofloxacino / N-Acetil Muramoil-L-Alanina Amidasa Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: Antimicrob Agents Chemother Año: 2014 Tipo del documento: Article País de afiliación: India Pais de publicación: Estados Unidos