Efficacy of Telavancin in Comparison to Linezolid in a Porcine Model of Severe Methicillin-Resistant Staphylococcus aureus Pneumonia.

Current guidelines recommend vancomycin and linezolid as first-line agents against methicillin-resistant Staphylococcus aureus (MRSA) nosocomial pneumonia. Telavancin is a potential new therapeutic alternative, specifically in monomicrobial MRSA pneumonia. This study compared the efficacies of telavancin versus linezolid in a porcine model of severe MRSA pneumonia. In 18 mechanically ventilated pigs (32.11 ± 1.18 kg), 75 ml of 106 CFU/ml of MRSA was administered into each pulmonary lobe. After the onset of pneumonia, pigs were randomized into three groups: a control group, a group receiving 22.5 mg/kg of body weight every 24 h (q24h) of telavancin, and a group receiving 10 mg/kg q12h of linezolid intravenously. Tracheal aspirate and bronchoalveolar lavage (BAL) fluids were cultured every 24 h. After 48 h of treatment, tissue samples were collected from the ventral and dorsal sections of each lobe. Microbiological and histopathological analyses were performed. Lung tissue concentrations differed among the groups (P = 0.019), with the lowest MRSA lung burden in the telavancin group (P < 0.05 versus the control). MRSA was detected in 46.7%, 40.0%, and 21.7% of the lung tissue samples from the control, linezolid, and telavancin groups, respectively (P < 0.001). MRSA concentrations differed among the groups in tracheal aspirate fluid (P = 0.011) but not in BAL fluid. Furthermore, there was no increased risk of kidney injury during telavancin use. Thus, telavancin has higher bactericidal efficacy than linezolid during the first 48 h of treatment in a porcine model of severe MRSA pneumonia. However, studies are needed to confirm the benefits of telavancin in treating MRSA nosocomial pneumonia.

Recruitment manoeuvres dislodge mucus towards the distal airways in an experimental model of severe pneumonia.

BACKGROUND: Recruitment manoeuvres generate a transient increase in trans-pulmonary pressure that could open collapsed alveoli. Recruitment manoeuvres might generate very high inspiratory airflows. We evaluated whether recruitment manoeuvres could displace respiratory secretions towards the distal airways and impair gas exchange in a porcine model of bacterial pneumonia. METHODS: We conducted a prospective randomised study in 10 mechanically ventilated pigs. Pneumonia was produced by direct intra-bronchial introduction of Pseudomonas aeruginosa. Four recruitment manoeuvres were applied randomly: extended sigh (ES), maximal recruitment strategy (MRS), sudden increase in driving pressure and PEEP (SI-PEEP), and sustained inflation (SI). Mucus transport was assessed by fluoroscopic tracking of radiopaque disks before and during each recruitment manoeuvre. The effects of each RM on gas exchange were assessed 15 min after the intervention. RESULTS: Before recruitment manoeuvres, mucus always cleared towards the glottis. Conversely, mucus was displaced towards the distal airways in 28.6% ES applications and 50% of all other recruitment manoeuvres (P=0.053). Median mucus velocity was 1.26 mm min-1 [0.48-3.89] before each recruitment manoeuvre, but was reversed (P=0.007) during ES [0.10 mm min-1 [-0.04-1.00]], MRS [0.10 mm min-1 [-0.4-0.48]], SI-PEEP [0.02 mm min-1 [-0.14-0.34]], and SI [0.10 mm min-1 [-0.63-0.75]]. When PaO2 failed to improve after recruitment manoeuvre, mucus was displaced towards the distal airways in 68.7% of the cases, compared with 31.2% recruitment manoeuvres associated with improved PaO2 (odds ratio: 4.76 (95% confidence interval: 1.13-19.97). CONCLUSIONS: Recruitment manoeuvres dislodge mucus distally, irrespective of airflow generated by different recruitment manoeuvres. Further investigation in humans is warranted to corroborate these pre clinical findings, as there may be limited benefits associated with lung recruitment in pneumonia.