Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
6118358 | International Journal of Antimicrobial Agents | 2011 | 6 Pages |
Abstract
Ceftobiprole is an investigational intravenous broad-spectrum cephalosporin with in vitro activity against Gram-positive and Gram-negative pathogens, including meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa. Pseudomonas aeruginosa is a frequent nosocomial pathogen, increasingly associated with complicated skin and skin-structure infections. Combination antimicrobial therapy is recommended as empirical therapy for serious infections where P. aeruginosa is suspected. Therefore, in this study the interaction of ceftobiprole with two other antipseudomonal agents (amikacin and levofloxacin) was investigated. Time-kill studies were performed for each single agent and for the combination of ceftobiprole 4 mg/L with either amikacin or levofloxacin at 0.5Ã, 1à and 2à the minimum inhibitory concentration. Five clinical isolates of P. aeruginosa as well as the P. aeruginosa ATCC 27853 reference strain were tested at initial inocula of 5 Ã 105 colony-forming units (CFU)/mL (low inoculum) or 5 Ã 107 CFU/mL (high inoculum). Synergy was defined as a decrease of â¥2 log10 CFU/mL with the combination compared with the most active single drug at 6 h and 24 h. At low inoculum with ceftobiprole as a single agent, viable counts were decreased by 1.5-2 log10 at 6 h. Addition of either amikacin or levofloxacin resulted in synergistic bactericidal activity at 24 h. At high inoculum the combination of ceftobiprole with amikacin or levofloxacin demonstrated synergism in one of three and three of five strains, respectively. This study demonstrated that the combination of ceftobiprole at a clinically achievable concentration of 4 mg/L with amikacin or levofloxacin exhibited synergistic activity against P. aeruginosa. There was no evidence of antagonism for either combination.
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Authors
Michael Kresken, Barbara Körber-Irrgang, Jörg Läuffer, Sabine Decker-Burgard, Todd Davies,