PURPOSE:Ventilator-associated pneumonia (VAP) remains a major cause of morbidity and mortality. Staphylococcus aureus (SA) in general, and methicillin-resistant SA (MRSA) in particular, represent leading pathogens in VAP. Telavancin (TLV) is an investigational lipoglycopeptide with enhanced activity against MRSA. The efficacy of TLV in SA VAP was evaluated in the ATTAIN program.
METHODS:We performed this subgroup analysis from 2 large, identical, randomized, double-blind, multinational trials comparing TLV 10 mg/kg every 24 hours (adjusted for creatinine clearance) with vancomycin (VAN) 1 g every 12 h (dose adjustments permitted per site standard protocols). The decision to pool these data was prospectively determined. Diagnosis of VAP was based on clinical and radiological criteria in patients receiving >2 d of mechanical ventilation. Microbiologically evaluable (ME) patients were those who received any study medication, whose outcomes could be determined, and from whom a Gram-positive pathogen was recovered at baseline (tracheal aspirate or lower airway). Clinical cure (e.g., resolution of signs and symptoms) at Test-of-cure visit (7–14 d after end of study therapy) represented the primary endpoint.
RESULTS:Overall, 1503 patients were treated; 28% had VAP. For patients with VAP, baseline characteristics were well balanced between treatment groups. TLV was non-inferior to VAN in the overall study population. 118 patients with VAP were ME; SA was implicated in 92% (n=109) of these patients. Clinical cure rates for SA VAP were 76.3% (45/59) for TLV and 60.0% (30/50) for VAN (treatment difference 16.9%, 95% confidence interval [CI] -1.2%, 32.8%). For MRSA VAP, clinical cure rates were 75.0% (27/36) for TLV and 57.6% (19/33) for VAN (difference 17.8%, 95% CI -5.1%, 37.2%). Cure rates were similar for methicillin-susceptible SA (MSSA): 79.2% (19/24) TLV vs. 64.7% (11/17) VAN (difference 15.7%, 95% CI -13.8%, 41.3%). The incidence of adverse events was similar between treatment groups.
CONCLUSION:This subgroup analysis suggests TLV is non-inferior to VAN for treatment of SA VAP.
CLINICAL IMPLICATIONS:TLV may represent a promising novel agent for VAP caused by both MSSA and MRSA.
DISCLOSURE:Andrew Shorr, Grant monies (from industry related sources) Astellas Pharma US, Ortho-MacNeil-Jansen, Pfizer; Consultant fee, speaker bureau, advisory committee, etc. Astellas Pharma US, Ortho-MacNeil-Jansen, Pfizer; Product/procedure/technique that is considered research and is NOT yet approved for any purpose. Telavancin