Antistaphylococcal Activity of Ceftobiprole, a New Broad-Spectrum Cephalosporin

Abstract

Ceftobiprole (formerly BAL9141), the active component of the prodrug BAL5788 (ceftobiprole medocaril), is a novel cephalosporin with expanded activity against gram-positive bacteria. Among 152 Staphylococcus aureus isolates, including 5 vancomycin-intermediate and 2 vancomycin-resistant strains, MIC 50 and MIC 90 values for ceftobiprole were each 0.5 g/ml against methicillin-susceptible strains and 2 g/ml against methicillinresistant strains. Against 151 coagulase-negative staphylococci (including 4 vancomycin-intermediate strains), MIC 50 and MIC 90 values were, respectively, 0.125 g/ml and 1 g/ml against methicillin-susceptible and 1 g/ml and 2 g/ml against methicillin-resistant strains. Teicoplanin was less active than vancomycin against coagulase-negative strains. Linezolid, quinupristin-dalfopristin, and daptomycin were active against all strains, whereas increased MICs for amoxicillin-clavulanate, cefazolin, minocycline, gentamicin, trimethoprim-sulfamethoxazole, levofloxacin, rifampin, mupirocin, fusidic acid, and fosfomycin were sometimes observed. At 2؋ MIC, ceftobiprole was bactericidal against 11 of 12 test strains by 24 h. Prolonged serial passage in the presence of subinhibitory concentrations of ceftobiprole failed to select for clones with MICs >4 times those of the parents; the maximum MIC achieved for ceftobiprole after 50 passages (in 1 of 10 strains) was 8 g/ml. Single-passage selections showed very low frequencies of resistance to ceftobiprole irrespective of genotype or phenotype; the maximal ceftobiprole MIC of recovered clones was 8 g/ml.The emergence of methicillin-and fluoroquinolone-resistant staphylococci and, more recently, glycopeptide-intermediate staphylococci (6,17,33,46) and the risk of serious infections posed by these strains (10, 42) necessitate alternative therapeutic modalities (9,31,32,44) Ceftobiprole (formerly BAL9141), the active component of the prodrug ceftobiprole medocaril (formerly BAL5788), is a novel parenteral cephalosporin whose broad spectrum of activity includes most clinically important gram-positive and gram-negative bacteria (23,29). Preliminary surveys have indicated that ceftobiprole has excellent in vitro activity against methicillin-resistant staphylococci, vancomycin-intermediate S. aureus (VISA), VRSA, and coagulase-negative staphylococci (8,14,20,23,29). The present study sought to determine (i) the MICs of ceftobiprole and 15 comparators against 303 staphylococci, (ii) the bacteriostatic or bactericidal activities of ceftobiprole and comparators against 12 selected staphylococcal strains, and (iii) the proclivity of ceftobiprole and some comparators to select for endogenous resistance from among 10 staphylococci with diverse resistotypes. .). Most strains studied, including MRSA, were isolated within the 5 years prior to the study. No information on whether strains were community acquired or nosocomial is available. MATERIALS AND METHODS BacteriaAntimicrobial agents and MIC testing. Ceftobiprole powder was obtained from Basilea Pharmaceutica AG (Ba...

Reduced Vancomycin Susceptibility inStaphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications

“…Ceftobiprole retained good activity against a small number of VISA and VRSA strains (MICs of Յ2 g per ml) (27). In a rabbit model of endocarditis due to MRSA and VISA, ceftobiprole was as effective as vancomycin against MRSA and superior to vancomycin against VISA (41).…”

“…Ceftobiprole has demonstrated good in vitro activity against MRSA strains, with an MIC 90 of 2 g per ml (27). Ceftobiprole retained good activity against a small number of VISA and VRSA strains (MICs of Յ2 g per ml) (27).…”

Single- and Multistep Resistance Selection Studies on the Activity of Retapamulin Compared to Other Agents against Staphylococcus aureus and Streptococcus pyogenes

“…Multipassage resistance selection was done as described previously (3,6). Daily passages were continued until a more-thanfour-fold increase in the MIC was found (minimum passage number, 14; maximum passage number, 50).…”

Emerging agents to combat complicated and resistant infections: focus on ceftobiprole

“…8,9 Spectrum of activity Ceftobiprole is active against S. aureus, including MRSA and vancomycin-intermediate S. aureus (VISA), coagulase-negative staphylococci (CNS), Enterococcus species (including vancomycin-resistant but not ampicillinresistant enterococci), pneumococci, some anaerobes, and Gram-negative bacilli (with similar activity to third-and fourth-generation cephalosporins, with the exception of Proteus vulgaris). 5,[10][11][12][13][14] Ceftobiprole is not active against extended-spectrum beta-lactamase (ESBL) producing strains of Enterobacteriaceae. 13,15,16 Published MIC data for a range of microorganisms are shown in Table 1.…”