The impact of mechanical ventilation on the moxifloxacin treatment of experimental pneumonia caused by Streptococcus pneumoniae

Charles, Pierre‐Emmanuel; Etienne, Manuel; Croisier, Delphine; Piroth, Lionel; Lequeu, Catherine; Pugin, Jérôme; Portier, H.; Chavanet, P.

doi:10.1097/01.ccm.0000163404.35338.72

Cited by 10 publications

(6 citation statements)

References 39 publications

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“…These results are consistent with our previous findings [ 19 , 21 , 22 , 27 , 28 ]. However, it is worth noting that some differences exist with respect to the pathogen involved.…”

Section: Discussionsupporting

confidence: 94%

“…In the spontaneously breathing (SB) group, the rabbits were orally intubated as previously described [ 21 , 22 ]. Briefly, under general anaesthesia provided by an intravenous injection of ketamine 3.3 milligrams (mg)/kg (Panpharma, France) and xylazine 1 mg/kg (Rompun ® , Bayer, Germany), a cuff tube of 3.0 mm was orally inserted into the trachea under view control.…”

Section: Methodsmentioning

confidence: 99%

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Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit

et al. 2016

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Ventilator-associated pneumonia (VAP) is common during mechanical ventilation (MV). Beside obvious deleterious effects on muco-ciliary clearance, MV could adversely shift the host immune response towards a pro-inflammatory pattern through toll-like receptor (TLRs) up-regulation. We tested this hypothesis in a rabbit model of Staphylococcus aureus VAP. Pneumonia was caused by airway challenge with S. aureus, in either spontaneously breathing (SB) or MV rabbits (n = 13 and 17, respectively). Pneumonia assessment regarding pulmonary and systemic bacterial burden, as well as inflammatory response was done 8 and 24 hours after S. aureus challenge. In addition, ex vivo stimulations of whole blood taken from SB or MV rabbits (n = 7 and 5, respectively) with TLR2 agonist or heat-killed S. aureus were performed. Data were expressed as mean±standard deviation. After 8 hours of infection, lung injury was more severe in MV animals (1.40±0.33 versus [vs] 2.40±0.55, p = 0.007), along with greater bacterial concentrations (6.13±0.63 vs. 4.96±1.31 colony forming units/gram, p = 0.002). Interleukin (IL)-8 and tumor necrosis factor (TNF)-αserum concentrations reached higher levels in MV animals (p = 0.010). Whole blood obtained from MV animals released larger amounts of cytokines if stimulated with TLR2 agonist or heat-killed S. aureus (e.g., TNF-α: 1656±166 vs. 1005±89; p = 0.014). Moreover, MV induced TLR2 overexpression in both lung and spleen tissue. MV hastened tissue injury, impaired lung bacterial clearance, and promoted a systemic inflammatory response, maybe through TLR2 overexpression.

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“…These results are consistent with our previous findings [ 19 , 21 , 22 , 27 , 28 ]. However, it is worth noting that some differences exist with respect to the pathogen involved.…”

Section: Discussionsupporting

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit

et al. 2016

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“…In the present study, we showed that although LNZ therapy was successful in SB rabbits, its efficacy was limited to the lung compartment in MV rabbits. Interestingly, our findings in our model of pneumococci pneumonia treated with moxifloxacin were similar [ 23 ]. No significant histological findings were likely to account for such a difference in extra-pulmonary bacterial diffusion, but unseen lung damage is not excluded.…”

Section: Discussionsupporting

confidence: 73%

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

Pauchard¹,

Blot²,

Bruyère³

et al. 2017

PLoS ONE

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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.

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“…Animals from the former group were immediately sacrificed by a lethal dose of penthotal, whereas the latter were orally intubated as previously described [8,9]. The animal was then connected to a pressure-controlled ventilator (Babylog ® ; Drager, Lübeck, Germany).…”

Section: Methodsmentioning

confidence: 99%

Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide

et al. 2011

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IntroductionMechanical ventilation (MV) could prime the lung toward an inflammatory response if exposed to another insult such as bacterial invasion. The underlying mechanisms are not so far clear. Toll-like receptors (TLRs) allow the host to recognize selectively bacterial pathogens and in turn to trigger an immune response. We therefore hypothesized that MV modulates TLR2 expression and in turn modifies responsiveness to agonists such as bacterial lipopeptide (BLP).MethodBoth in vitro and in vivo experiments were conducted. First, TLR2 expression and protein were measured in the A549 pulmonary epithelial cell line submitted to 8-hour cyclic stretch (20% elongation; 20/minute rate). After a 24-hour period of cyclic stretch, the inflammatory response of the A549 cells to the synthetic BLP, Pam3CSK4, was tested after 8 hours of exposure. In a second set of experiments, healthy anesthetized and paralyzed rabbits were submitted to 8-hour MV (tidal volume = 12 ml/kg, zero end-expiratory pressure; FIO2 = 50%; respiratory rate = 20/minute) before being sacrificed for TLR2 lung expression assessment. The lung inflammatory response to BLP was then tested in animals submitted to 24-hour MV before being sacrificed 8 hours after the tracheal instillation of Pam3CSK4.ResultsCyclic stretch of human pulmonary epithelial cell lines increased both TLR2 mRNA and protein expression. Cells submitted to cyclic stretch also increased IL-6 and IL-8 secretion in response to Pam3CSK4, a classical TLR2 ligand. A mild-stretch MV protocol induced a 60-fold increase of TLR2 mRNA expression in lung tissue when compared with spontaneously breathing controls. Moreover, the combination of MV and airway exposure to Pam3CSK4 acted synergistically in causing lung inflammation and injury.ConclusionsMild-stretch MV increases lung expression of TLR2 and sensitizes the lung to bacterial TLR2 ligands. This may account for the propensity of mechanically ventilated patients to develop acute lung injury in the context of airway bacterial colonization/infection.

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The impact of mechanical ventilation on the moxifloxacin treatment of experimental pneumonia caused by Streptococcus pneumoniae

Cited by 10 publications

References 39 publications

Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit

Mechanical Ventilation Alters the Development of Staphylococcus aureus Pneumonia in Rabbit

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

Mild-stretch mechanical ventilation upregulates toll-like receptor 2 and sensitizes the lung to bacterial lipopeptide

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