Abstract
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.
Highlights
Methicillin-resistant Staphylococcus aureus (MRSA) in both community and ventilator-associated pneumonia (VAP) is frequent in some countries
Statin treatment prior to pneumonia did not improve linezolid efficacy There was a trend toward a reduction of the pulmonary bacterial load in spontaneously breathing (SB) and in mechanical ventilation (MV) rabbits treated with LNZ, without any improvement in tissue damage (Figs 1 and 2)
Whereas no bacteremia was detected in the SB treated rabbits, LNZ failed apparently to prevent MRSA systemic spillover in MV animals since 59% of them had positive spleen cultures (Fig 1)
Summary
Methicillin-resistant Staphylococcus aureus (MRSA) in both community and ventilator-associated pneumonia (VAP) is frequent in some countries. The highest clinical success rates did not exceed 57% despite appropriate antibiotics [1]. Experimental evidence suggests that mechanical ventilation (MV) could cause specific lung damage (i.e., ventilator-induced lung injury [VILI]) [2]. Antibiotics and statins in experimental pneumonia (i.e., Aspire grant) has provided support in the form of the remaining research materials, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript
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