2. Academic Validation
  3. Susceptibility of multidrug-resistant Escherichia coli and Klebsiella pneumoniae to oral antibiotics in Australia

Susceptibility of multidrug-resistant Escherichia coli and Klebsiella pneumoniae to oral antibiotics in Australia

  • J Glob Antimicrob Resist. 2025 Aug 8:44:435-441. doi: 10.1016/j.jgar.2025.08.002.
Bethany Rachel O'Neill 1,  Andrew Ginn 2,  Menuk Jayawardena 3,  Indy Sandaradura 4
Affiliations

Affiliations

  • 1 The University of Sydney, New South Wales, Australia. Electronic address: bone5748@alumni.sydney.edu.au.
  • 2 Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology - Institute of Clinical Pathology and Medical Research, Westmead, New South Wales, Australia; Sydney Institute for Infectious Diseases, The University of Sydney, New South Wales, Australia; Douglass Haly Moir Pathology, Macquarie Park, New South Wales, Australia.
  • 3 Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology - Institute of Clinical Pathology and Medical Research, Westmead, New South Wales, Australia.
  • 4 The University of Sydney, New South Wales, Australia; Centre for Infectious Diseases and Microbiology Laboratory Services, New South Wales Health Pathology - Institute of Clinical Pathology and Medical Research, Westmead, New South Wales, Australia; Sydney Institute for Infectious Diseases, The University of Sydney, New South Wales, Australia.
PMID: 40784378 DOI: 10.1016/j.jgar.2025.08.002
Abstract

Objectives: In Australia, resistance to β-lactam-class Antibiotics in Enterobacterales has increased. This study aimed to identify potential oral treatments for these multidrug-resistant infections by investigating four β-lactam (mecillinam, tebipenem, sulopenem, and faropenem) and three non-β-lactam (fosfomycin, omadacycline, and delafloxacin) Antibiotics, and to elucidate the genetic resistance mechanisms.

Methods: Seventy-four Escherichia coli and 24 Klebsiella pneumoniae, with extended-spectrum β-lactamase or plasmid-mediated AmpC β-lactamases genes, were isolated from New South Wales hospital patients in 2021. Minimum inhibitory concentrations (MICs) were determined using Clinical and Laboratory Standards Institute (CLSI) guidelines with agar dilution for fosfomycin and mecillinam, and broth microdilution for the remaining Antibiotics. Multiplex polymerase chain reaction and whole genome Sequencing (Illumina) confirmed Bacterial resistance mechanisms.

Results: The E. coli were mostly susceptible to mecillinam (97%), and had low MIC90 to tebipenem, sulopenem, and faropenem (0.125 mg/L, 0.5 mg/L, and 4 mg/L). K. pneumoniae were mostly susceptible to mecillinam (96%), and had a low MIC90 to tebipenem and sulopenem, but higher MIC90 to faropenem (2 mg/L, 2 mg/L, and 8 mg/L). Moreover, the cases of E. coli were mostly susceptible to fosfomycin and omadacycline, but not delafloxacin (100%, 95%, and 16%); K. pneumoniae susceptibilities to these Antibiotics were 92%, 50%, and 17%, respectively. Resistance mechanisms include tet(A) and ramR mutations for omadacycline; gyrA, parC, and qnr mutations for delafloxacin; and ompK36 gene deletions for fosfomycin, mecillinam, tebipenem, sulopenem, and faropenem.

Conclusions: The favourable results support the use of mecillinam, tebipenem, sulopenem, faropenem, fosfomycin, and omadacycline against multidrug-resistant E. coli. Mecillinam, sulopenem, and fosfomycin may be useful for multidrug-resistant K. pneumoniae in Australia.

Keywords

Enterobacterales; Oral antibiotics; Urinary tract infection (UTI).

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