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Original Research: PNEUMONIA |

Effect of Linezolid Compared With Glycopeptides in Methicillin-Resistant Staphylococcus aureus Severe Pneumonia in Piglets

Carlos M. Luna, MD, PhD, FCCP; Didier A. Bruno, MD; Joaquín García-Morato, MD; Keli C. Mann, MD; Juan Risso Patrón, MD; Judith Sagardía, MD; Rubén Absi, PhD; Milagros García Bottino, PhD; Diana Marchetti, PhD; Angela Famiglietti, PhD; Mónica Baleztena, MD; Cesar Biancolini, MD
Author and Funding Information

*From the Department of Medicine (Drs. Luna, Bruno, and Risso Patrón), Experimental Surgery University Center (Drs. García-Morato, Sagardía, and Biancolini), and the Department of Pathology (Dr. Baleztena), Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica (Drs. Absi, García Bottino, Marchetti, and Famiglietti), Universidad de Buenos Aires, Buenos Aires, Argentina; and the Department of Pulmonary Medicine (Dr. Mann), Universidade Federal do Rio Grande Do Sul, Porto Alegre, Brazil.

Correspondence to: Carlos M. Luna, MD, PhD, FCCP, Hospital de Clínicas, Universidad de Buenos Aires, Internal Medicine, Acevedo 1070, Banfield (1828), Buenos Aires, Argentina; e-mail: cymluna@advancedsl.com.ar


This study was funded by an independent research grant from Pfizer, which was administered by the Asociación Cooperadora del Hospital de Clínicas.

Dr. Luna has served on the advisory boards for Bayer (for which he received $1,500), Wyeth (for which he received $1,500), and Pfizer (for which he received $1,500), and has been a speaker for AstraZeneca (for which he received $2,000). Drs. Bruno, García-Morato, Mann, Risso Patrón, Sagardía, Absi, García Bottino, Marchetti, Famiglietti, Baleztena, and Biancolini have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/site/misc/reprints.xhtml).


© 2009 American College of Chest Physicians


Chest. 2009;135(6):1564-1571. doi:10.1378/chest.08-2169
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Objectives:  To investigate if compared with glycopeptides, antimicrobial therapy (AMT) with linezolid (LZD) improves the outcome in methicillin-resistant Staphylococcus aureus (MRSA) experimental pneumonia in mechanically ventilated piglets.

Methods:  The MRSA minimal inhibitory concentration (MIC) was 0.5 for vancomycin (VAN), 0.25 for teicoplanin (TEI), and 2.0 μg/mL for LZD was inoculated in Largewhite-Landrace piglets divided into five groups. One group (n = 6) did not receive mechanical ventilation (MV) or AMT. Those in the remaining groups received MV and VAN (n = 9), TEI (n = 7), LZD (n = 9), or no AMT (n = 7). Plasma and BAL tumor necrosis factor-α, interleukin-6, and C-reactive protein (CRP) concentrations, postmortem lung pathology, cultures (lung, blood, and BAL) and plasma, epithelial lining fluid (ELF), and lung antibiotic concentrations were evaluated.

Measurements and main results:  All piglets developed severe pneumonia; lung pathology score was lower in those receiving LZD vs those receiving glycopeptides (p = 0.049) or no AMT (p = 0.037). Serum CRP and serum and BAL cytokines increased; there were no differences between the groups. Fourteen died spontaneously at 44.4 ± 16.8 h; the remaining 24 were killed after 72 to 96 h. The concentrations of the antimicrobial agents tested in 15 piglets were higher than the MIC for the three antimicrobial agents in peak and trough plasma, ELF, and lung specimens. Survival at 72 h was higher in the LZD comparing with the no-AMT group.

Conclusions:  Inoculation produced severe MRSA pneumonia. LZD AMT was associated with lower pathology score, better survival, and a trend to better clearance of MRSA, not attributable exclusively to pharmacokinetic or pharmacodynamic reasons.

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