Recent molecules in the treatment of severe infections caused by ESBL-producing bacteria

ABSTRACT

Introduction: The widespread increase in resistance to β-lactam antibiotics in Enterobacterales currently represents one of the main threats to human health worldwide. The primary mechanisms of resistance are the production of β-lactamase enzymes that are able to hydrolyze β-lactams.

Areas covered: we summarize the most recent advances regarding the main characteristics and spectrum of activity of new available antibiotics and strategies for the treatment of ESBL-producing Enterobacterales infections.

Expert opinion: ESBL-producing strains are recognized as a worldwide challenge in the treatment of both hospital- and community-acquired infections. Data from the literature point out the high mortality associated with severe infections due to ESBL strains, especially in patients who developed severe sepsis or septic shock, together with the importance of the source of infection and indicators of severity, as determinants of the patient’s outcome. Carbapenems are currently considered the first-line therapy, although the diffusion of resistant strains is an evolving problem and is mandatory the introduction in clinical practice of new drug regimens and treatment strategies, based on clinical data, local epidemiology, and microbiology. As a possible carbapenem-sparing strategy, ceftolozane–tazobactam and ceftazidime–avibactam appear the best-available carbapenem-sparing therapies. The definitive role of new drugs should be definitively assessed.

KEYWORDS:

• ESBL
• carbapenem
• septic shock
• new antibiotics
• ceftolozane–tazobactam
• ceftazidime–avibactam

Article highlights

- ESBL-producing strains are recognized as a worldwide challenge for physicians

- New drug regimens and treatment strategies should be based on clinical data, local epidemiology, and microbiology

- Carbapenems are currently considered the first-line therapy, but the diffusion of resistant strains is a dramatic problem

- As a possible carbapenem-sparing strategy, ceftolozane–tazobactam and ceftazidime–avibactam appear the best-available therapies

- Cefiderocol is a potentially good alternative, but further studies are necessary to validate its use in clinical practice

Declaration of interest

The authors have no 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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.