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Daptomycin combinations as alternative therapies in experimental foreign-body infection caused by

Cristina El Haj1, Oscar Murillo1, Alba Ribera1

  • 1Laboratory of Experimental Infection, Infectious Diseases Service, IDIBELL, Hospital Universitari de Bellvitge, Feixa Llarga s/n, 08907 L'Hospitalet de Llobregat, Barcelona, Spain.

International Journal of Antimicrobial Agents
|June 9, 2015
PubMed

Insights

Daptomycin plus rifampicin (DAP+RIF) and daptomycin plus levofloxacin (DAP+LVX) are effective alternatives for prosthetic joint infections caused by MSSA. DAP+RIF showed superior efficacy and prevented antibiotic resistance.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Microbiology

Background:

  • Prosthetic joint infections (PJI) caused by meticillin-susceptible Staphylococcus aureus (MSSA) typically use levofloxacin (LVX) and rifampicin (RIF).
  • Limited therapeutic alternatives exist for MSSA PJI, necessitating evaluation of novel combinations.
  • Daptomycin (DAP) has shown efficacy against meticillin-resistant S. aureus (MRSA) PJI, suggesting potential for MSSA treatment.

Purpose of the Study:

  • To evaluate the efficacy of daptomycin plus rifampicin (DAP+RIF) and daptomycin plus levofloxacin (DAP+LVX) as alternative therapies for foreign-body infections (FBIs) caused by MSSA.
  • To compare the efficacy of these combinations against monotherapies and assess the emergence of antibiotic resistance.

Main Methods:

  • A rat tissue-cage infection model using an MSSA strain was employed.
  • Animals were treated with monotherapies (LVX, DAP, RIF) or combination therapies (LVX+RIF, DAP+RIF, DAP+LVX) for 7 days.
  • Efficacy was assessed by bacterial counts in tissue cage fluid (TCF) and cure rates based on adhered bacteria; resistance screening was performed.

Main Results:

  • Combination therapies were significantly more effective than monotherapies (P<0.05).
  • DAP+RIF demonstrated the highest efficacy with a -4.9logCFU/mL decrease in bacterial counts and a 92% cure rate.
  • DAP+LVX (47% cure rate) and LVX+RIF (11% cure rate) showed varied efficacy, with no resistance emerging in combined therapies.

Conclusions:

  • Daptomycin-based combinations, particularly DAP+RIF, are effective alternative therapies for MSSA FBIs, including PJI.
  • DAP+RIF exhibited superior efficacy compared to LVX+RIF and prevented the emergence of antibiotic resistance.
  • Further research is warranted to explore DAP+RIF as a potential first-line treatment for MSSA PJI.
Keywords:
Combination therapyDaptomycinForeign-body infectionMSSA

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