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Antimicrobial salvage therapy for persistent staphylococcal bacteremia using daptomycin plus ceftaroline.

George Sakoulas1, Pamela A Moise2, Anthony M Casapao3

  • 1University of California San Diego School of Medicine, La Jolla, California.

Clinical Therapeutics
|July 15, 2014
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Summary

Ceftaroline combined with daptomycin effectively treated refractory staphylococcal bacteremia, including methicillin-resistant Staphylococcus aureus (MRSA). This combination therapy rapidly cleared bloodstream infections and showed synergistic effects in laboratory studies.

Keywords:
MRSAMRSE bacteremiaMSSAVISAceftarolinedaptomycin

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Area of Science:

  • Infectious Diseases
  • Clinical Microbiology
  • Pharmacology

Background:

  • Guidelines suggest daptomycin combination therapy for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia post-vancomycin failure.
  • Emerging data indicate potential benefits of combining daptomycin with beta-lactams.
  • Clinical data on ceftaroline and daptomycin combination therapy remain limited.

Purpose of the Study:

  • To evaluate the clinical use and outcomes of ceftaroline plus daptomycin for refractory staphylococcal bacteremia.
  • To investigate the in vitro and in vivo effects of ceftaroline and daptomycin combination therapy.

Main Methods:

  • Retrospective case series of 26 patients treated with ceftaroline plus daptomycin for staphylococcal bacteremia across 10 medical centers.
  • In vitro studies including synergy, binding assays, and cathelicidin LL-37 killing assays.
  • In vivo virulence assays using a murine subcutaneous infection model.

Main Results:

  • The combination was used in 26 cases of staphylococcal bacteremia (20 MRSA, 2 VISA, 2 MSSA, 2 MRSE).
  • Median time to bacteremia clearance was 2 days after initiating ceftaroline plus daptomycin, compared to a median of 10 days on prior therapy.
  • In vitro studies demonstrated ceftaroline synergy with daptomycin against MRSA and enhanced killing by LL-37 and neutrophils.

Conclusions:

  • Ceftaroline plus daptomycin may accelerate the clearance of refractory staphylococcal bacteremia.
  • Ceftaroline enhances daptomycin activity and sensitizes MRSA to innate immune defenses, potentially attenuating virulence.