Safety profiles of old and new antimicrobials for the treatment of MRSA infections

ABSTRACT

Introduction: Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of severe nosocomial and community-acquired infections. Various adverse effects have been associated with compounds that are commonly used in the treatment of MRSA.

Areas covered: Prolonged use of high-dose vancomycin has been linked with nephrotoxicity. Linezolid use has been associated with lactic acidosis in regimens longer than 14 days and occurrence of thrombocytopenia in patients with renal impairment. Daptomycin use correlates with reversible and often asymptomatic myopathy. Among new compounds, telavancin has shown increased toxicity compared to vancomycin, especially in patients with severe renal impairment, while a low rate of adverse effects was reported others glycolipopeptides such as dalbavancin and oritavancin and for new cephalosporins. Recently studied oxazolidinones (tedizolid and radezolid) also showed mild adverse effects in Phase 2 and 3 clinical trials.

Expert opinion: Due to the constant increase in antimicrobial resistance, the use of higher doses and prolonged regimens of antibiotics employed in the treatment of Gram-positive infections has become more common and linked to increased toxicity. Furthermore, new compounds with MRSA activity have been recently approved and will be regularly employed in clinical practice. The knowledge of the adverse effects and risk factors for the development of toxicity associated with anti-MRSA antimicrobials is paramount for the correct use of old and new compounds, especially in the treatment of severe infections.

KEYWORDS:

• MRSA
• drug toxicity
• new cephalosporins
• daptomycin
• glycopeptides
• oxazolidinones

Article highlights.

• The use of increased doses and prolonged regimens in ‘real-world studies’ has been associated over the years with reports of new adverse effects, such as hematological toxicity for linezolid and nephrotoxicity for vancomycin.

• Among new oxazolidinones, tedizolid has been associated with a favorable safety profile, while radezolid still has to be evaluated in Phase 3 trials.

• Daptomycin displays a safe profile even at high doses (>6 mg/kg), with reversible myopathy being a rare and reversible adverse effect.

• Ceftaroline and ceftobiprole have shown adverse effects similar to other cephalosporins and comparable to standard therapy in Phase 3 trials.

• Telavancin has shown more frequently adverse effects compared to vancomycin and higher mortality in patients with severe renal impairment and should be used with caution in this group.

• Long-lasting glycolipopeptides (dalbavancin and oritavancin) have shown a better safety profile compared to vancomycin.

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Declaration of interest

M Bassetti declared associated with Astellas, Pfizer, Gilead, Novartis, Tetraphase, Achaogen and MSD. 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.