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

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.