Clinical pharmacological approach for balancing the use of daptomycin and linezolid in comparison with that of vancomycin in the treatment of MRSA-related infections

Abstract

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most challenging bacterial pathogens responsible for severe infections among hospitalized patients. In recent years there is increasing evidence that the clinical efficacy of vancomycin is progressively decreasing. Although daptomycin and linezolid are valuable alternatives to vancomycin for the treatment of MRSA-related bloodstream infections and pneumonia, respectively, a great deal of debate exists about their role in daily clinical practice due to cost-effectiveness issues. In this article we put into perspective the importance of pharmacokinetic/pharmacodynamic (PK/PD) considerations based on recent experimental and clinical data to argue whether they could be helpful in identifying clinical conditions in which these agents could be advantageous as compared to vancomycin.

Keywords:

• pharmacokinetic/pharmacodynamic
• daptomycin
• linezolid
• MRSA
• pneumonia
• bloodstream infections

Financial & competing interests disclosure

F Pea has accepted speaking and conference invitations for Astra Zeneca, Gilead, Merk Sharp & Dohme, Novartix and Pfizer, and has had recent or ongoing scientific advisory boards with Astra Zeneca, Boehringer Ingelheim and Pfizer. N Petrosillo has accepted speaking and conference invitations from Astellas, Carefusion, Johnson & Johnson, MSD, Novartis and Pfizer, and has had recent or ongoing scientific advisory boards with Achaogen, Astellas, Carefusion, The Medicnines Company, MSD, Novartis and Pfizer. J Garau has accepted grants, speaking and conference invitations from Astellas, AstraZenica, Bayer, Cubist Pharmaceuticals, Novartis, Pfizer, The Medicines Company, and Vifor Pharma and has had recent or ongoing consultancy with AstraZenica, Bayer, Cubist Pharmaceuticals, Durata, GSK, Janssen-Cilag, Novartis, Theravance and Vifor Pharma. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Clinical efficacy of vancomycin against methicillin-resistant Staphylococcus aureus (MRSA)-related infections is progressively decreasing.

• Pharmacokinetic/pharmacodynamic strategies could be helpful in balancing the use of daptomycin and linezolid in comparison with that of vancomycin in the treatment of MRSA-related infections.

• The role of daptomycin in the treatment of MRSA-related bloodstream infections (BSI) might be especially beneficial in presence of clinical isolates with high vancomycin MIC and/or in patients with severe sepsis/ septic shock.

• Daptomycin dosages up to 8–10 mg/kg/day may be necessary for optimal exposure in patients with augmented renal clearance.

• Combination of daptomycin with rifampin could be helpful in preventing the development of resistance, especially when treating device-related infections.

• The role of linezolid in the treatment of MRSA-related pneumonia might be especially beneficial in the presence of clinical isolates with high vancomycin MIC and/or in patients with severe sepsis/ septic shock.

• The immunomodulatory activity of linezolid could be helpful in lowering the high mortality rate which is observed in MRSA-pneumonia when it is associated with severe sepsis or with septic shock.

• De-escalation from daptomycin/ linezolid to oxacillin or to vancomycin should be resolutely pursued whenever feasible.

Notes