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Antimicrobial Agents and Chemotherapy, April 2009, p. 1546-1551, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00979-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Tigecycline Therapy Significantly Reduces the Concentrations of Inflammatory Pulmonary Cytokines and Chemokines in a Murine Model of Mycoplasma pneumoniae Pneumonia{triangledown}

C. M. Salvatore,1 C. Techasaensiri,1 C. Tagliabue,4 K. Katz,1 N. Leos,3 A. M. Gomez,3 G. H. McCracken,1 and R. D. Hardy1,2*

Departments of Pediatric Infectious Diseases,1 Internal Medicine,2 Pathology, University of Texas Southwestern Medical Center, Dallas, Texas,3 Department of Pediatrics, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy4

Received 22 July 2008/ Returned for modification 10 September 2008/ Accepted 2 January 2009

Mycoplasma pneumoniae is one of the causative agents of atypical community-acquired pneumonia. Tigecycline belongs to a new class of glycylcycline antimicrobials that have activity against a wide range of microorganisms, including in vitro activity against M. pneumoniae. We investigated the effect of tigecycline on microbiologic, histologic, and immunologic indices in a murine model of M. pneumoniae pneumonia. BALB/c mice were inoculated intranasally with M. pneumoniae and treated subcutaneously with tigecycline or placebo for 6 days. Outcome variables included quantitative bronchoalveolar lavage (BAL) M. pneumoniae culture, lung histopathologic score (HPS), BAL cytokine and chemokine concentrations (tumor necrosis factor alpha [TNF-{alpha}], gamma interferon [IFN-{gamma}], interleukin 1β [IL-1β], IL-2, IL-4, IL-5, IL-6, IL-10, IL-12 [p40/p70], granulocyte-macrophage colony-stimulating factor, MIP-1{alpha}, MIG, KC, MCP-1, and IP-10). BAL M. pneumoniae concentrations in mice treated with tigecycline (MpTige) tended to be reduced compared with mice treated with placebo (MpPl); however this did not reach statistical significance. The lung HPS was significantly lower, as well as the parenchymal-pneumonia subscore, in the MpTige mice than in the MpPl mice. MpTige mice had significantly lower BAL cytokine concentrations of IL-1β, IL-12 (p40/p70), IFN-{gamma}, and TNF-{alpha}; of the chemokines, MIG, MIP-1{alpha}, and IP-10 were statistically lower in MpTige mice. While tigecycline treatment demonstrated a modest microbiologic effect, it significantly improved lung histologic inflammation and reduced pulmonary cytokines and chemokines.

* Corresponding author. Mailing address: Department of Internal Medicine and Pediatrics, Divisions of Infectious Diseases, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063. Phone: (214) 648-3720. Fax: (214) 648-2961 or (214) 648-9091. E-mail: RDougHardy{at}msn.com

{triangledown} Published ahead of print on 12 January 2009.

Antimicrobial Agents and Chemotherapy, April 2009, p. 1546-1551, Vol. 53, No. 4
0066-4804/09/$08.00+0     doi:10.1128/AAC.00979-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Zhanel, G. G., Baudry, P. J., Tailor, F., Cox, L., Hoban, D. J., Karlowsky, J. A. (2009). Determination of the pharmacodynamic activity of clinically achievable tigecycline serum concentrations against clinical isolates of Escherichia coli with extended-spectrum {beta}-lactamases, AmpC {beta}-lactamases and reduced susceptibility to carbapenems using an in vitro model. J Antimicrob Chemother 64: 824-828 [Abstract] [Full Text]  


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