In Vitro Activity of Tebipenem (SPR859) against Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria

Antimicrob Agents Chemother. 2019 Mar 27;63(4):e02181-18. doi: 10.1128/AAC.02181-18. Print 2019 Apr.

Abstract

Tebipenem (SPR859) is the microbiologically active form of SPR994 (tebipenem-pivoxil), an orally available carbapenem with activity against extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae Measurement of the relative binding of SPR859 to the bacterial cell targets revealed that it is a potent inhibitor of multiple penicillin-binding proteins (PBPs) but primarily a Gram-negative PBP 2 inhibitor, similar to other compounds in this class. These data support further clinical development of SPR994.

Keywords: PBP; carbapenems; penicillin-binding proteins; tebipenem.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / antagonists & inhibitors*
  • Bacterial Proteins / metabolism
  • Carbapenems / pharmacology*
  • Gram-Negative Bacteria / drug effects*
  • Gram-Negative Bacteria / metabolism
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / metabolism
  • Humans
  • Microbial Sensitivity Tests / methods
  • Penicillin-Binding Proteins / antagonists & inhibitors*
  • Penicillin-Binding Proteins / metabolism
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Carbapenems
  • Penicillin-Binding Proteins
  • beta-Lactamases
  • tebipenem