Abstract
Carbapenem-resistant Klebsiella pneumoniae has globally emerged as an urgent threat leading to the limitation for treatment. K. pneumoniae carrying blaOXA-48, 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 blaOXA-48-carrying K. pneumoniae. 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 blaOXA-48-carrying plasmids conferred carbapenem resistance in Escherichia coli 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 blaOXA-48-carrying K. pneumoniae infection during a recent shortage of newly effective antibiotic development.
Highlights
Carbapenem resistance in Enterobacteriaceae is currently a global concern [1]
Among nine blaOXA-48 -carrying K. pneumoniae isolates, seven isolates were resistant to all tested carbapenems, whereas KP203 and
Fosfomycin and azithromycin showed an efficient effect on only three and two isolates, respectively. These results indicate that all isolates were multidrugresistant (MDR) strains; they were resistant to at least three antibiotic classes, including carbapenems, extended-spectrum cephalosporins, and fluoroquinolones (Table 1)
Summary
Carbapenem resistance in Enterobacteriaceae is currently a global concern [1]. AmongEnterobacteriaceae, Klebsiella pneumoniae plays a major role in resistance to carbapenems [2,3].Most K. pneumoniae isolates are resistant to carbapenem by carbapenemase production [2,4].Apart from metallo-carbapenemases (such as NDM and IMP) and an Ambler class A carbapenemase (KPC) that strongly hydrolyze carbapenemases, OXA-48 produces a weak carbapenemase activity yet is responsible for a broad range of carbapenem susceptibility [4]. Enterobacteriaceae, Klebsiella pneumoniae plays a major role in resistance to carbapenems [2,3]. Most K. pneumoniae isolates are resistant to carbapenem by carbapenemase production [2,4]. Apart from metallo-carbapenemases (such as NDM and IMP) and an Ambler class A carbapenemase (KPC) that strongly hydrolyze carbapenemases, OXA-48 produces a weak carbapenemase activity yet is responsible for a broad range of carbapenem susceptibility [4]. Among carbapenemase-producing K. pneumoniae, 13.7% were OXA-48 producers that displayed susceptible and resistant phenotypes [9]. In addition to carbapenemase production, the loss of outer membrane proteins (OMPs) (OmpK35 and OmpK36) which act as the carbapenem entry portal, plays a role in carbapenem susceptibility [10].
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