Pearls and pitfalls of oral carbapenem/penem agents: the promise of a new era or the risk of amplified resistance?

Abstract

Introduction: The rising prevalence of MDR Gram-negative infections, particularly ESBL-producing Enterobacterales, has created a critical oral treatment gap, necessitating prolonged intravenous therapy. Oral carbapenems/penems offer a long-awaited opportunity to bridge this gap.

Areas covered: This review examines the chemistry, pharmacokinetics/pharmacodynamics, and phase 3 trial evidence for tebipenem and sulopenem, recently FDA-approved for urinary tract infections (UTI). We analyze the regulatory landscape pearls and pitfalls of these agents, and their management through an outpatient antimicrobial stewardship (AMS) perspective. Literature was searched in PubMed, Scopus, ClinicalTrials.gov, and regulatory databases through June 2026.

Expert opinion: Oral carbapenems/penems evoke enthusiasm over closing a long-standing oral treatment gap for MDR Gram-negative infections, alongside apprehension regarding resistance risks. With both agents now approved in the United States, this promise is now a reality, marking the start of a new era in oral therapy. However, global regulatory fragmentation and evidence limited to UTIs remain key barriers to broader clinical use. Crucially, growing use may shift carbapenem selection pressure from hospitals into the community. This risk requires strict resistance surveillance and formulary restriction to confirmed MDR infections lacking oral alternatives. Their clinical trajectory will depend less on intrinsic activity than on the rigor of AMS frameworks governing their use.