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

Autor: Keli C. Mann, Juan Risso Patrón, Diana Marchetti, Angela Famiglietti, Didier Bruno, Milagros García Bottino, Rubén Absi, Joaquín García-Morato, Mónica Baleztena, C. A. Biancolini, Judith Sagardía, Carlos M. Luna
Rok vydání: 2009
Předmět:
Methicillin-Resistant Staphylococcus aureus
Pulmonary and Respiratory Medicine
medicine.medical_specialty
Swine
medicine.drug_class
Antibiotics
Critical Care and Intensive Care Medicine
medicine.disease_cause
Sensitivity and Specificity
Severity of Illness Index
Gastroenterology
Drug Administration Schedule
Random Allocation
chemistry.chemical_compound
Internal medicine
Acetamides
Pneumonia
Staphylococcal
medicine
Animals
Oxazolidinones
Probability
Antibacterial agent
Analysis of Variance
Dose-Response Relationship
Drug
Teicoplanin
business.industry
Biopsy
Needle
Glycopeptides
Linezolid
Ventilator-associated pneumonia
medicine.disease
Immunohistochemistry
Respiration
Artificial
Methicillin-resistant Staphylococcus aureus
Survival Rate
Disease Models
Animal
Pneumonia
Treatment Outcome
chemistry
Immunology
Vancomycin
Cardiology and Cardiovascular Medicine
business
medicine.drug
Zdroj: Chest. 135:1564-1571
ISSN: 0012-3692
DOI: 10.1378/chest.08-2169
Popis: 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.
Databáze: OpenAIRE
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