Ceftobiprole alone versus ampicillin-ceftriaxone against borderline-penicillin-resistant, ampicillin-susceptible, and vancomycin-resistant Enterococcus faecalis isolates

TL;DR

This study compares ceftobiprole and ampicillin-ceftriaxone against drug-resistant Enterococcus faecalis, finding ceftobiprole more effective in some cases.

Contribution

The study evaluates ceftobiprole's efficacy against borderline-penicillin-resistant and vancomycin-resistant E. faecalis isolates.

Findings

Ceftobiprole showed greater activity than ampicillin-ceftriaxone against borderline-penicillin-resistant E. faecalis.

Ceftobiprole was more effective than ampicillin-ceftriaxone against vancomycin-resistant E. faecalis isolates.

Combining ceftobiprole with ampicillin improved efficacy in some isolates but showed potential antagonism in others.

Abstract

Despite the use of recommended treatments against Enterococcus faecalis infective endocarditis, mortality rates remain at 30%. Penicillin-resistant, ampicillin-susceptible E. faecalis (PRASEF) has been associated with worsened clinical outcomes; however, a more common phenotype, borderline-PRASEF (penicillin minimum inhibitory concentration [MIC] 4–8 µg/mL), decreases the activity of ampicillin-ceftriaxone in vitro. Ceftobiprole presents a promising alternative against borderline-PRASEF and also has shown activity against vancomycin-resistant E. faecalis (VREfs). The ceftobiprole MIC distribution was determined via broth microdilution for 78 E. faecalis clinical blood isolates, including 71 borderline-PRASEF. Ceftobiprole activity alone was compared to ampicillin-ceftriaxone via in vitro 24-hour time-kill assays against 30 E. faecalis isolates, 24 of which were borderline-PRASEF and 15 were VREfs. Ceftobiprole and ceftriaxone were tested at physiologic concentrations (fCpss 13.9 µg/mL and 17.2 mcg/mL, respectively) and ampicillin at subinhibitory concentrations (0.25 × MIC and 0.5 × MIC). Isolates where ceftobiprole alone had limited activity were tested against ceftobiprole-ampicillin. Ceftobiprole maintained activity against borderline-PRASEF compared to ampicillin-ceftriaxone. Ceftobiprole also demonstrated more activity against VREfs isolates and isolates with an elevated ceftobiprole MIC ≥16 µg/mL, compared to ampicillin-ceftriaxone. Ceftobiprole did not achieve ≥2 log10 CFU/mL kill in six isolates but was able to achieve this once combined with ampicillin. When tested at ampicillin inhibitory concentrations, ceftobiprole-ampicillin activity trended towards antagonism in two isolates. Overall, ceftobiprole alone had greater activity compared to ampicillin-ceftriaxone, and there may be a potential role of ceftobiprole combination therapy in certain isolates.

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