title: Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets.
abstract: OBJECTIVE
  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 microg/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-alpha, 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.
  
  
  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.
authors.affiliation: Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: cymluna@advancedsl.com.ar.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Luna
authors.affiliation: Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Didier A
authors.initials: DA
authors.lastname: Bruno
authors.affiliation: Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Joaquín
authors.initials: J
authors.lastname: García-Morato
authors.affiliation: Department of Pulmonary Medicine, Universidade Federal do Rio Grande Do Sul, Porto Alegre, Brazil.
authors.forename: Keli C
authors.initials: KC
authors.lastname: Mann
authors.affiliation: Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Juan
authors.initials: J
authors.lastname: Risso Patrón
authors.affiliation: Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Judith
authors.initials: J
authors.lastname: Sagardía
authors.affiliation: Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Rubén
authors.initials: R
authors.lastname: Absi
authors.affiliation: Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Milagros
authors.initials: M
authors.lastname: García Bottino
authors.affiliation: Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Diana
authors.initials: D
authors.lastname: Marchetti
authors.affiliation: Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Angela
authors.initials: A
authors.lastname: Famiglietti
authors.affiliation: Department of Pathology, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Mónica
authors.initials: M
authors.lastname: Baleztena
authors.affiliation: Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Cesar
authors.initials: C
authors.lastname: Biancolini
mesh_terms: D000081:Acetamides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006020:Glycopeptides / Q000494:pharmacology*; D007150:Immunohistochemistry; D000069349:Linezolid; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D023303:Oxazolidinones / Q000494:pharmacology*; D011023:Pneumonia, Staphylococcal / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D011336:Probability; D011897:Random Allocation; D012121:Respiration, Artificial; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D015996:Survival Rate; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; D006020:Glycopeptides; D023303:Oxazolidinones; D000069349:Linezolid