Review of novel β-lactams and β-lactam/β-lactamase inhibitor combinations with implications for pediatric use

Pharmacotherapy. 2023 Jul;43(7):713-731. doi: 10.1002/phar.2782. Epub 2023 Mar 12.

Abstract

Antimicrobial resistance continues to surmount increasing concern globally, and treatment of difficult-to-treat (DTR) Pseudomonas aeruginosa, carbapenem-resistant (CR) Acinetobacter baumannii (CRAB), and CR Enterobacterales (CRE) remains a challenge for clinicians. Although previously rare, the incidence of multidrug-resistant (MDR) and CR infections in pediatric patients has increased drastically in the last decade and is associated with increased morbidity and mortality. To combat this issue, 14 novel antibiotics, including three β-lactam/novel β-lactamase inhibitor combinations (βL-βLIs) and two novel β-lactams (βLs), have received approval from the United States Food and Drug Administration since 2010. Improving clinician understanding of the utility of these novel therapies is imperative to improve judicious decision-making and prevent societal regression to a pre-penicillin era. In this review, we summarize the pharmacokinetic/pharmacodynamic (PK/PD) properties, clinical efficacy and safety data, dosing considerations, and subsequent role in therapy for ceftazidime-avibactam (CAZ-AVI), meropenem-vaborbactam (MER-VAB), imipenem-cilastatin-relebactam (IMI-REL), ceftolozane-tazobactam (TOL-TAZ), and cefiderocol in pediatric patients.

Keywords: bacterial resistance; beta-lactams; pediatrics.

Publication types

  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Azabicyclo Compounds / pharmacology
  • Azabicyclo Compounds / therapeutic use
  • Child
  • Drug Combinations
  • Humans
  • Lactams*
  • Microbial Sensitivity Tests
  • United States
  • beta-Lactamase Inhibitors* / pharmacology
  • beta-Lactamase Inhibitors* / therapeutic use

Substances

  • beta-Lactamase Inhibitors
  • Lactams
  • Anti-Bacterial Agents
  • Drug Combinations
  • Azabicyclo Compounds