Telavancin Safe, Effective for Gram-Positive Bloodstream Infections in Cancer Patients

PHILADELPHIA, PA—The antibiotic telavancin was generally well tolerated and had a safety profile similar to vancomycin in patients with cancer and bloodstream infections, results of a prospective study presented at IDWeek 2014 have shown.

“Telavancin may offer another therapeutic option for the treatment of bacteremia caused by susceptible isolates of gram-positive bacteria,” reported Ray Hachem, MD, Professor and Director of the Infectious Diseases Trainee & Observership Program of the University of Texas, MD Anderson Cancer Center in Houston.

Vancomycin, the most commonly used antibiotic for the treatment of resistant gram positive cocci bacteremia, is often not active against strains with MICs >1mg/L. Telavancin, a once-daily injectable semi-synthetic lipoglycopeptide, has a dual mechanism of action that combines inhibition of cell wall synthesis and disruption of bacterial cell membrane function.

Dr. Hachem and colleagues evaluated the clinical efficacy and safety of telavancin for gram-positive bacteremia in 39 patients with uncomplicated gram-positive bloodstream infections. Telavancin was administered intravenously for at least 14 days for S. aureus and 7 days for other gram-positive cocci. Patients with baseline creatinine clearance (CrCl) >50mL/min received a daily dose of 10mg/kg; those with CrCl between 30–49mL/min received a dose of 7.5mg/kg.

Patients were followed for 1 month after the last dose of the study drug and were compared with 39 historical matched control patients (based on underlying disease, type of organism, and neutropenia) who were treated with vancomycin.

Among the 78 patients analyzed (39 in each group), the most common pathogens causing bloodstream infections were S. aureus (51%), alpha-hemolytic Streptococci (23%), Enterococcus (15%), coagulase-negative Staphylococcus (8%), and beta-hemolytic Streptococci (3%). A total of 62% of patients had hematological malignancies and, at onset of bacteremia, 51% were neutropenic.

Compared with vancomycin, telavancin was associated with better clinical response, defined as resolution of all symptoms, (88.9% vs. 74.4%; P=0.11). Microbiological response within 96 hours after starting either agent was similar (telavancin, 91.7% vs. vancomycin, 92.1%).Overall response, defined as clinical and microbiological response at 96 hours in the absence of relapse, complication, and infection-related mortality, was 83.3% (30 of 36 patients) in the telavancin group and 63.2% (24 of 38 patients) in the vancomycin group (P=0.051).

Overall mortality was 18.0% in the telavancin group and 12.8% in the vancomycin group (P=0.53) Drug-related adverse events were similar in both groups; 5 of the patients (12.8%) in the telavancin group had acute kidney injury, compared with 6 (15.4%) in the vancomycin group (P=0.74). Median creatinine levels and creatinine clearance at baseline, end-of-treatment, and last follow-up visits were comparable in both groups.

Telavancin is approved for the treatment of complicated skin and skin structure infections and for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia.

 

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