Linezolid and atorvastatin impact on pneumonia caused by Staphyloccocus aureus in rabbits with or without mechanical ventilation

• Published in: PloS one 2017-11, Vol.12 (11), p.e0187187-e0187187
• Main Authors: Pauchard, Laure-Anne, Blot, Mathieu, Bruyere, Rémi, Barbar, Saber-Davide, Croisier, Delphine, Piroth, Lionel, Charles, Pierre-Emmanuel
• Format: Article
• Language: English
• Subjects: Animals; Antibiotics; Atorvastatin; Bacteremia; Bacterial pneumonia; Biology and Life Sciences; Breathing; Cancer; Causes of; Complications and side effects; Critical care; Diagnosis; Dosage and administration; Drug resistance; Drug therapy; Inflammation; Inflammatory response; Intensive care; Laboratory animals; Life Sciences; Linezolid; Lungs; Mechanical ventilation; Medicine; Medicine and Health Sciences; Methicillin; Mortality; Nutrition; Other; Pneumonia; Rabbits; Research and Analysis Methods; Respiration; Sepsis; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Statins; TLR2 protein; Toll-like receptors; Tumor necrosis factor-α; Ventilation; Ventilators
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0187187

Pneumonia may involve methicillin-resistant Staphylococcus aureus (MRSA), with elevated rates of antibiotics failure. The present study aimed to assess the effect of statins given prior to pneumonia development. Spontaneously breathing (SB) or mechanically ventilated (MV) rabbits with pneumonia received atorvastatin alone, linezolid (LNZ) alone, or a combination of both (n = 5 in each group). Spontaneously breathing and MV untreated infected animals (n = 11 in each group), as well as uninfected animals (n = 5 in each group) were used as controls. Microbiological features and inflammation were evaluated. Data are presented as medians (interquartile range). Linezolid alone tended to reduce pulmonary MRSA load in both SB and MV rabbits, but failed to prevent bacteremia (59%) in the latter. Linezolid alone dampened TNF-α lung production in both SB and MV rabbits (e.g., 2226 [789] vs. 11478 [10251] pg/g; p = 0.022). Statins alone did the same in both SB and MV animals (e.g., 2040 [133]; p = 0.016), and dampened systemic inflammation in the latter, possibly through TLR2 down-regulation within the lung. However, the combination of LNZ and statin led to an increased rate of bacteremia in MV animals up to 75%. Statins provide an anti-inflammatory effect in rabbits with MRSA pneumonia, especially in MV ones. However, dampening the systemic inflammatory response with statins could impede blood defenses against MRSA.