Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in piglets.
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.
Luna
Carlos M
CM
Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina. Electronic address: cymluna@advancedsl.com.ar.
Bruno
Didier A
DA
Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
García-Morato
Joaquín
J
Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
Mann
Keli C
KC
Department of Pulmonary Medicine, Universidade Federal do Rio Grande Do Sul, Porto Alegre, Brazil.
Risso Patrón
Juan
J
Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
Sagardía
Judith
J
Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
Absi
Rubén
R
Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
García Bottino
Milagros
M
Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Marchetti
Diana
D
Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Famiglietti
Angela
A
Hospital de Clínicas, and the Facultad de Farmacia y Bioguímica, Universidad de Buenos Aires, Buenos Aires, Argentina.
Baleztena
Mónica
M
Department of Pathology, Universidad de Buenos Aires, Buenos Aires, Argentina.
Biancolini
Cesar
C
Experimental Surgery University Center, Universidad de Buenos Aires, Buenos Aires, Argentina.
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
D000081:Acetamides; D006020:Glycopeptides; D023303:Oxazolidinones; D000069349:Linezolid