Eravacycline for the treatment of complicated intra-abdominal infections

ABSTRACT

Introduction: Complicated intra-abdominal infections (cIAIs) are among the most frequent infections, contributing to significant morbidity and healthcare costs. Several medical needs remain unmet, related to the pharmacokinetic capacities of the available drugs and their limited spectrum of activity for targeting multidrug-resistant Gram-negative and Gram-positive bacteria. Eravacycline, a new synthetic fluorocycline, could have useful properties in cIAIs.

Areas covered: The antimicrobial activity of eravacycline against the microorganisms most frequently cultured in cIAIs has been confirmed in worldwide panels of clinical isolates, including enterococci, ESBL-producing Enterobacteriaceae, Acinetobacter baumannii and anaerobes. Pharmacokinetic data demonstrate interesting characteristics with good tissue concentrations including biliary tract and digestive tissues. At a conventional dosage of 1 mg/kg q12h, no adjustment is required on the basis of race or gender, or in elderly (≥ 65 years old) patients, patients with renal impairment or patients undergoing hemodialysis. Phase 2 and 3 trials assessing the clinical efficacy and safety of eravacycline demonstrated non-inferiority versus carbapenems and a good safety profile.

Expert opinion: Eravacycline may be particularly suitable for the treatment of cIAIs. Results from clinical trials and real-world data are now expected in specific subgroups of patients to confirm the safety profile and efficacy observed in registration trials.

KEYWORDS:

• Fluorocycline
• complicated intra-abdominal infection
• enterococci
• Enterobacteriaceae
• multidrug-resistant bacteria

Article highlights

• The spectrum of activity of eravacycline includes a broad range of anaerobic strains and Gram-positive and Gram-negative aerobic organisms commonly associated with cIAIs, including MRSA, enterococci and Enterobacteriaceae.

• Eravacycline presents interesting pharmacokinetic characteristics, with a high volume of distribution, highly protein-bound, prolonged half-life, no active metabolites, and no dosage adjustment based on age, gender or renal function.

• Eravacycline has demonstrated good IV bioavailability, allowing twice daily dosing.

• In two recent phase 3, multicenter, randomized, double-blind studies, eravacycline demonstrated non-inferiority compared to ertapenem and meropenem in terms of clinical response, microbiological success and post-treatment evaluation.

• Intravenous formulations appear to be safe and well tolerated with limited adverse events

Declaration of interest

P Montravers has received honoraria from Bayer, Menarini, MSD, Parexel, and Pfizer. 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.

Reviewer disclosures

Tetraphase Pharmaceuticals provided a scientific accuracy review at the request of the journal editor. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.