# Resistance of Uropathogens to Tebipenem: An Analysis of the Evidence from In Vitro Antimicrobial Susceptibility Studies

## TL;DR

This paper reviews how well tebipenem, a new antibiotic, works against bacteria that cause urinary tract infections, especially drug-resistant strains.

## Contribution

The study provides a comprehensive analysis of tebipenem's in vitro antimicrobial activity against uropathogens, including multidrug-resistant strains.

## Key findings

- Tebipenem showed strong activity against Escherichia coli and Klebsiella pneumoniae with low MIC90 values.
- Higher MICs and resistance were observed in Proteus mirabilis isolates.
- Tebipenem may be effective for outpatient treatment of multidrug-resistant Gram-negative infections.

## Abstract

Tebipenem is a new carbapenem antibiotic that binds to penicillin-binding proteins (PBPs). Given the need for effective antibiotics against multidrug-resistant (MDR) bacteria, this review evaluated the in vitro antimicrobial activity of tebipenem against Gram-negative and Gram-positive bacteria, focusing on uropathogens. Five resources (Google Scholar, Web of Science, Embase, Scopus, and PubMed) were used to identify relevant articles. Of the 1322 articles identified, 9 relevant studies were included, which evaluated 12,501 Gram-negative and 122 Gram-positive pathogens. All nine studies (100%) assessed the activity of tebipenem against Escherichia coli, with an MIC90 value range of 0.015–>4 mg/L. Seven studies (77.8%) included Klebsiella pneumoniae, with an MIC90 value range of 0.015–0.5 mg/L. Six studies (66.7%) reported data on Proteus mirabilis, with an MIC90 value range of ≤0.125–0.5 mg/L. Two studies (22.2%) evaluated the activity of tebipenem against Enterococcus faecalis, with MIC90 of 1 mg/L among vancomycin-susceptible isolates and 32 mg/L in isolates with not-reported mechanisms of resistance. Two studies (22.2%) evaluated the activity of tebipenem against Enterococcus faecium, with MIC90 of >4 mg/L among both vancomycin-susceptible and vancomycin-resistant isolates and MIC90 of 128 mg/L among isolates with no resistance mechanism reported. Tebipenem demonstrated good activity against Enterobacterales, such as E. coli and K. pneumoniae. The antimicrobial agent exhibited higher MICs and a higher proportion of resistance among P. mirabilis isolates. Tebipenem could be effective for outpatient treatment of infections caused by MDR Gram-negative pathogens. However, given its potential to exert selective pressure for the development of antimicrobial resistance, it should be considered for patients with cUTIs when none of the first-line treatment options demonstrate in vitro antimicrobial activity.