telavancin and Pneumonia

Telavancin (Vibativ(®)), a lipoglycopeptide antibacterial agent, exhibits potent in vitro activity against Gram-positive bacteria associated with nosocomial pneumonia infections, including meticillin/oxacillin-resistant Staphylococcus aureus (MRSA) isolates and S. aureus isolates with reduced susceptibility to vancomycin. In two multinational trials in adult patients with nosocomial pneumonia caused by Gram-positive bacteria, including infections caused by MRSA isolates, a 1-h intravenous infusion of telavancin 10 mg/kg once daily was noninferior to intravenous vancomycin 1 g every 12 h in terms of clinical cure rates in the all-treated (AT) and clinically evaluable (CE) populations at the follow-up/test-of-cure (FU/TOC) visit. At this visit, clinical cure rates in the AT populations of both groups were approximately 60 %, with rates increasing to ≥80 % in the CE population. Pooled analyses of these trials also generally showed no significant between-group differences in clinical cure rates at the FU/TOC visit in the AT, CE and microbiologically evaluable (ME) populations. In the ME population, clinical cure rates were generally similar in the telavancin and vancomycin groups, irrespective of whether infections were mono- or polymicrobial, or caused by MRSA or methicillin/oxacillin-susceptible S. aureus isolates. Telavancin was generally well tolerated in patients with nosocomial pneumonia participating in clinical trials, with a tolerability profile that was generally similar to that of vancomycin. Telavancin offers an alternative treatment option in patients with nosocomial pneumonia caused by Gram-positive S. aureus, including those caused by MRSA and S. aureus isolates with reduced susceptibility to vancomycin.

Topics: Aminoglycosides; Anti-Bacterial Agents; Clinical Trials as Topic; Cross Infection; Humans; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Pneumonia; Staphylococcal Infections

U.S. Food and Drug Administration draft guidance for future antibiotic clinical trials of bacterial nosocomial pneumonia recommends the use of diagnostic criteria according to American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines and the use of a primary endpoint of 28-day all-cause mortality. The effect of applying these guidelines on outcomes of phase III nosocomial pneumonia studies of telavancin was evaluated in a post hoc analysis. ATS/IDSA criteria were applied in a blind fashion to the original all-treated (AT) group. Clinical cure rates at final follow-up were determined in the refined AT and clinically evaluable (CE) groups (ATS/IDSA-AT and ATS/IDSA-CE, respectively). The exploratory endpoint of 28-day survival was evaluated for the ATS/IDSA-AT group. Noninferiority of telavancin versus vancomycin was demonstrated, with similar cure rates in the ATS/IDSA-AT (59% versus 59%) and ATS/IDSA-CE (83% versus 80%) groups. Cure rates favored telavancin in ATS/IDSA-CE patients where Staphylococcus aureus was the sole pathogen (86% versus 75%). Overall, 28-day survival rates were similar in the telavancin (76%) and vancomycin (77%) groups but lower in telavancin-treated patients with preexisting moderate-to-severe renal impairment (creatinine clearance [CLCR] of <50 ml/min). Telavancin should be administered to patients with moderate-to-severe renal impairment only if treatment benefit outweighs the risk or if no suitable alternatives are available.

Topics: Adult; Aged; Aged, 80 and over; Aminoglycosides; Anti-Bacterial Agents; Cross Infection; Female; Humans; Lipoglycopeptides; Male; Middle Aged; Pneumonia; Staphylococcus aureus; United States; Vancomycin

Telavancin displays potent in vitro and in vivo activity against methicillin-resistant Staphylococcus aureus (MRSA), including strains with reduced susceptibility to vancomycin. We compared the efficacies of telavancin and vancomycin against MRSA strains with vancomycin MICs of ≥1 μg/ml in a neutropenic murine lung infection model. Thirteen clinical MRSA isolates (7 vancomycin-susceptible, 2 vancomycin-heteroresistant [hVISA], and 4 vancomycin-intermediate [VISA] isolates) were tested after 24 h, and 7 isolates (1 hVISA and 4 VISA isolates) were tested after 48 h of exposure. Mice were administered subcutaneous doses of telavancin at 40 mg/kg of body weight every 12 h (q12h) or of vancomycin at 110 mg/kg q12h; doses were designed to simulate the area under the concentration-time curve for the free, unbound fraction of drug (fAUC) observed for humans given telavancin at 10 mg/kg q24h or vancomycin at 1 g q12h. Efficacy was expressed as the 24- or 48-h change in lung bacterial density from pretreatment counts. At dose initiation, the mean bacterial load was 6.16 ± 0.26 log(10) CFU/ml, which increased by averages of 1.26 ± 0.55 and 1.74 ± 0.68 log in untreated mice after 24 and 48 h, respectively. At both time points, similar CFU reductions were noted for telavancin and vancomycin against MRSA, with vancomycin MICs of ≤2 μg/ml. Both drugs were similarly efficacious after 24 and 48 h of treatment against the hVISA strains tested. Against VISA isolates, telavancin reduced bacterial burdens significantly more than vancomycin for 1 of 4 isolates after 24 h and for 3 of 4 isolates after 48 h. These data support the potential utility of telavancin for the treatment of MRSA pneumonia caused by pathogens with reduced susceptibility to vancomycin.

Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Disease Models, Animal; Female; Lipoglycopeptides; Methicillin-Resistant Staphylococcus aureus; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Pneumonia; Staphylococcal Infections; Vancomycin