A multicentre study to determine the in vitro efficacy of flomoxef against extended-spectrum beta-lactamase producing Escherichia coli in Malaysia

PeerJ. 2023 Nov 28:11:e16393. doi: 10.7717/peerj.16393. eCollection 2023.

Abstract

Background: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.

Methods: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated.

Results: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.

Keywords: Antimicrobial resistance; Enterobacterales; Escherichia coli; Extended-spectrum beta-lactamase (ESBL); Flomoxef; Surgical site infection.

Publication types

  • Multicenter Study

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Carbapenems / pharmacology
  • Escherichia coli / genetics
  • Escherichia coli Infections* / drug therapy
  • Humans
  • Malaysia / epidemiology
  • beta-Lactamases / genetics

Substances

  • Anti-Bacterial Agents
  • beta-Lactamases
  • Carbapenems
  • flomoxef

Grants and funding

This research was funded by the Ministry of Higher Education (Malaysia), Transdisciplinary Research Grant Scheme, TRGS (TRGS/1/2020/UM/02/2/2) under project code TR001B-2020 and Shionogi Singapore Pte. Ltd (IF015-2018). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.