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Effect of linezolid compared with glycopeptides in methicillin-resistant Staphylococcus aureus severe pneumonia in
Carlos M Luna1, Didier A Bruno1, Joaquín García-Morato2
1Department of Medicine, Universidad de Buenos Aires, Buenos Aires, Argentina.
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 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.
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.
Insights
Linezolid (LZD) antimicrobial therapy (AMT) improved outcomes in piglets with methicillin-resistant Staphylococcus aureus (MRSA) pneumonia compared to glycopeptides or no treatment. LZD AMT was associated with lower lung pathology scores and better survival rates.
Area of Science:
- Infectious Diseases
- Pulmonology
- Pharmacology
Background:
- Methicillin-resistant Staphylococcus aureus (MRSA) poses a significant threat in healthcare settings.
- Pneumonia in mechanically ventilated patients is associated with high morbidity and mortality.
- Antimicrobial resistance necessitates the evaluation of alternative treatment strategies.
Purpose of the Study:
- To compare the efficacy of linezolid (LZD) versus glycopeptides for treating experimental MRSA pneumonia in mechanically ventilated piglets.
- To assess the impact of LZD antimicrobial therapy (AMT) on lung pathology, survival, and inflammatory markers.
Main Methods:
- A porcine model of MRSA pneumonia was established in mechanically ventilated piglets.
- Animals were randomized to receive vancomycin, teicoplanin, LZD, or no antimicrobial therapy.
- Lung pathology, bacterial cultures, inflammatory markers (CRP, cytokines), and antibiotic concentrations were evaluated.
Main Results:
- All piglets developed severe MRSA pneumonia.
- LZD treatment resulted in significantly lower lung pathology scores compared to glycopeptides or no AMT.
- Survival at 72 hours was higher in the LZD group compared to the no-AMT group.
- Antibiotic concentrations in plasma and lung tissue exceeded the minimal inhibitory concentration (MIC).
Conclusions:
- Linezolid antimicrobial therapy (AMT) demonstrates improved outcomes in experimental MRSA pneumonia in piglets.
- LZD treatment is associated with reduced lung pathology and enhanced survival.
- The benefits of LZD are not solely explained by pharmacokinetic or pharmacodynamic properties.
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