| Summary: | Carbapenem-resistant <i>Klebsiella pneumoniae</i> has globally emerged as an urgent threat leading to the limitation for treatment. <i>K. pneumoniae</i> carrying <i>bla</i><sub>OXA-48</sub>, which plays a broad magnitude of carbapenem susceptibility, is widely concerned. This study aimed to characterize related carbapenem resistance mechanisms and forage for new antibiotic combinations to combat <i>bla</i><sub>OXA-48</sub>-carrying <i>K. pneumoniae</i>. Among nine isolates, there were two major clones and a singleton identified by ERIC-PCR. Most isolates were resistant to ertapenem (MIC range: 2–>256 mg/L), but two isolates were susceptible to imipenem and meropenem (MIC range: 0.5–1 mg/L). All <i>bla</i><sub>OXA-48</sub>-carrying plasmids conferred carbapenem resistance in <i>Escherichia coli</i> transformants. Two ertapenem-susceptible isolates carried both outer membrane proteins (OMPs), OmpK35 and OmpK36. Lack of at least an OMP was present in imipenem-resistant isolates. We evaluated the in vitro activity of an overlooked antibiotic, azithromycin, in combination with other antibiotics. Remarkably, azithromycin exhibited synergism with colistin and fosfomycin by 88.89% and 77.78%, respectively. Bacterial regrowth occurred after exposure to colistin or azithromycin alone. Interestingly, most isolates were killed, reaching synergism by this combination. In conclusion, the combination of azithromycin and colistin may be an alternative strategy in dealing with <i>bla</i><sub>OXA-48</sub>-carrying <i>K. pneumoniae</i> infection during a recent shortage of newly effective antibiotic development.
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