Tebipenem, the first oral carbapenem antibiotic

ABSTRACT

Introduction: Infections caused by antibiotic-resistant pathogens, particularly Gram-negative bacteria, have become increasingly challenging to successfully treat. The beta-lactam antibiotic subclass, the carbapenems, have proven valuable for the treatment of such Gram-negative bacterial infections due to their spectrum and β-lactamase stability properties. However, all marketed carbapenems to date are parenterally administered to adult patients.

Areas covered: One carbapenem, tebipenem-pivoxil (TBPM-PI), is an oral prodrug that was approved in Japan for pediatric use only in 2009. This review summarizes preclinical and clinical data for TBPM-PI, which is now in clinical development again this time for use as the first oral carbapenem available for treatment of bacterial infections in adult patients.

Expert commentary: There is an urgent unmet need with an increasing prevalence of fluoroquinolone-resistant and ESBL-producing Gram-negative pathogens in the hospital and community setting. Carbapenems have traditionally been considered the drugs of choice for infections caused by enterobacteria producing ESBL and AmpC enzymes because they are not affected by these resistance mechanisms. The carbapenem, TBPM-PI, offers an oral option, particularly as step-down therapy, for use of this class in the treatment of serious Gram-negative infections.

KEYWORDS:

• Antibiotic resistance
• beta-lactam
• carbapenem
• extended-spectrum beta-lactamase (ESBL)
• penicillin-binding protein

Acknowledgments

The authors would like to acknowledge Tim Kuetzer, Cristina Larkin, and David Melnick for helpful discussions. The authors also thank Meiji Seika Pharma Co., Ltd. for sharing unpublished data with us and for assistance in ensuring accuracy in this review.

Declaration of Interest

The authors are employees of Spero Therapeutics, Inc., which is developing tebipenem-pivoxil (SPR994) as an oral carbapenem antibiotic for adult patients. Spero has an agreement with Meiji Seika Pharma Co., Ltd. for worldwide market rights except for the following countries: Japan, Bangladesh, Brunei, Cambodia, China, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, South Korea, Taiwan, Thailand and Vietnam. 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

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

Additional information

Funding

The manuscript was not funded.