Ceftobiprole, an advanced cephalosporin, was highly active against most clinical isolates of the major Gram-positive and Gram-negative skin and soft tissue infection (SSTI) pathogen groups collected at medical centers in the United States, according to data presented at American Society of Microbiology (ASM) Microbe 2019 held from June 20-24, 2019, in San Francisco, California.

Ceftobiprole medocaril, the prodrug of ceftobiprole, is approved in many European and non-European countries but not in the United States. It does have qualified infectious disease product status and is undergoing 2 phase 3 clinical trials.

In the presented study, ceftobiprole and comparator activities were evaluated against those of more than 7300 clinical isolates collected from patients with SSTIs. Susceptibility to ceftobiprole or comparator agents was tested using current Clinical and Laboratory Standards Institute methods. Clinical and Laboratory Standards Institute and European Committee on Antimicrobial Susceptibility Testing (EUCAST) interpretive criteria were applied according to current guidelines.

The major species and pathogen groups included were Staphylococcus aureus (53.3%), Enterobacteriaceae sp (23.3%), Pseudomonas aeruginosa (7.2%), β-hemolytic streptococci (6.4%), Enterococcus spp (3.9%), and coagulase-negative streptococci (2.5%). 

Ceftobiprole was highly active against S aureus (minimum inhibitory concentration [MIC]50/90 values, 0.5/1 mg/L; 99.8% susceptible by EUCAST criteria). The MIC50/90 values increased 2-fold (99.4% susceptible) against the methicillin-resistant S aureus subset.

Potent activity was also exhibited by ceftobiprole against other Gram-positive cocci such as, β-hemolytic streptococci (MIC50/90 values, 0.015/0.03 mg/L; 100% inhibited at ≤4 mg/L, the EUCAST pharmacokinetic/pharmacodynamic nonspecies related breakpoint), Enterococcus faecalis (MIC50/90 values 0.5/2 mg/L; 99.6% inhibited ≤4 mg/L), and coagulase-negative streptococci (MIC50/90 values 0.5/1 mg/L; 100% inhibited ≤4 mg/L). Overall, the susceptibility of Enterobacteriaceae to ceftobiprole was 85.0% (98.0% susceptible for the non-extended spectrum beta-lactamase phenotype subset) and 74.0% of P aeruginosa isolates were inhibited at ≤4 mg/L. Ceftobiprole was mostly inactive against Enterobacteriaceae that exhibited an extended spectrum beta-lactamase phenotype and Enterococcus faecium, but this was expected.

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Overall ceftobiprole was highly active against the collected clinical isolates. According to investigators, this broad-spectrum activity, which included potent activity against methicillin-resistant S aureus, warrants further evaluation for this potential indication.

Reference

Duncan LR, Hamed K, Smart JI, Mendes RE, Pfaller MA, Flamm RK. Ceftobiprole activity against pathogens causing bacterial skin and soft tissue infections in the United States from 2016 through 2018. Presented at: ASM Microbe 2019; June 20-24, 2019; San Francisco, CA. Poster P506.