Safety evaluation of current therapies for high-risk severely ill patients with carbapenem-resistant infections

ABSTRACT

Introduction

Infections due to carbapenem-resistant Gram-negative bacteria (CR-GNB) are increasingly frequent events, which are associated with a high mortality rate. Traditionally, combination regimens including high doses of “old antibiotics” such as polymyxins, tigecycline, and aminoglycosides have been used to treat these infections, but they were often associated with low efficacy and high excess of side effects and toxicity, especially nephrotoxicity. Along with the development of new compounds, the last decade has seen substantial improvements in the management of CR infections.

Areas covered

In this review, we aimed to discuss the safety characteristics and tolerability of different new options for treatment of CR infections.

Expert opinion

The availability of new drugs showing a potent in vitro activity against CR-GNB represents a unique opportunity to face the threat of resistance, while potentially reducing toxicity. A thorough understanding of the safety profile from clinical trials may guide the use of these new drugs in critically ill patients at high risk for the development of adverse events. Future data coming from real-life studies for drugs targeting CR infections are crucial to confirm the safety profile observed in pivotal trials.

KEYWORDS:

• Carbapenem-resistant infections
• carbapenemases
• drug toxicity
• acute kidney injury
• new antibiotics

Article highlights

• The increasing incidence of carbapenem-resistant Gram-negative bacteria represents an urgent public health concern as they have spread worldwide.

• Among old antibiotics, regimens including high-dose colistin or aminoglycosides have been associated with increased rates of relevant side effects and non-negligible toxicity.

• New antimicrobials that have been recently approved in clinical practice (e.g. ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam, cefiderocol, eravacycline, and plazomicin) are usually well-tolerated with a favorable safety profile.

• Future real-world studies are needed to confirm the efficacy and safety observed in randomized clinical trials.

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Declaration of interests

Outside the submitted work, M Bassetti has received funding for scientific advisory boards and travel and speaker honoraria from Angelini, Astellas, AstraZeneca, Basilea, Bayer, BioMérieux, Cidara, Correvio, Cubist, Menarini, Molteni, MSD, Nabriva, Paratek, Pfizer, Roche, Shionogi, Tetraphase, Thermo Fisher, and The Medicine Company. Outside the submitted work, DR Giacobbe reports honoraria from Stepstone Pharma GmbH and unconditional grants from MSD Italia and Correvio Italia. 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This paper was not funded.