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Journal of Medical Microbiology logo Journal of Medical Microbiology

Volume 72, Issue 10

Efficacy of ceftobiprole in a murine model of bacteremia and disseminated infection Open Access

Abstract

Ceftobiprole is an advanced-generation broad-spectrum parenteral cephalosporin with activity against MSSA and MRSA.

Ceftobiprole is not currently approved for use to treat bacteremia and phase three clinical trials are taking place. Drug approval requires further pre-clinical evidence to support this new indication.

The aim of this study was to evaluate the efficacy of ceftobiprole at the human equivalent efficacious exposure (considering a 500 mg q8h dosing regimen infused over 2 h) against MSSA and MRSA strains in a neutropenic murine model of bacteremia and disseminated infection.

Two bioluminescent-tagged strains (one MSSA and one MRSA strain) were selected based on their susceptibility and growth profiles. Bacterial c.f.u. counts in the blood, lung, kidney, and liver were determined 48 h post-infection or after death. The bioluminescent-tag allowed the visualization of the real-time effects of ceftobiprole therapy compared to the natural progression of the infection in untreated controls.

Treatment with ceftobiprole resulted in a significant reduction of the bacterial load with the bioluminescence reduced by 2-log units and bacterial c.f.u. counts reduced by 3- to 6-log units, depending on the organ and bacterial strain. Survival was 100 % in the ceftobiprole-treated group compared to only 0–20 % survival in the untreated control animals for both strains tested.

These results suggest that treatment with ceftobiprole using a 500 mg q8h dosing regimen studied in several successful phase three trials, has potential as an antibiotic therapy to treat bacteremia and associated disseminated infections caused by either methicillin-susceptible or methicillin-resistant strains of .

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): antibiotic , bacteremia , Ceftobiprole , cephalosporin , MRSA and MSSA
Funding
This study was supported by the:
  • Biomedical Advanced Research and Development Authority (Award HHSO100201600002C)
    • Principle Award Recipient: NotApplicable
© 2023 Basilea Pharmaceutical Inc.
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2023-10-04
2025-01-25
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Efficacy of ceftobiprole in a murine model of bacteremia and disseminated infection
J. Med. Microbiol. 72, 001755 (2023); https://doi.org/10.1099/jmm.0.001755
/content/journal/jmm/10.1099/jmm.0.001755
/content/journal/jmm/10.1099/jmm.0.001755
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