Abstract

Carbapenem-resistant Enterobacterales (CRE) is an increasing problem worldwide. Here, we examined the clonal relatedness of 71 non-repetitive CRE isolates collected in a university hospital in Tehran, Iran, between February 2015 and March 2016. Pulsed-field gel electrophoresis (PFGE) and MLST were used for epidemiological analysis. Screening for antibiotic resistance genes, PCR-based replicon typing, conjugation experiments, and optical DNA mapping were also performed. Among all 71 isolates, 47 isolates of Klebsiella pneumoniae (66.2%), eight Escherichia coli (11.2%), five Serratia marcescens (7%), and two Enterobacter cloacae (2.8%) harbored blaNDM–1 and blaOXA–48 genes together or alone. PFGE analysis revealed that most of the OXA-48- and NDM-1-producing K. pneumoniae and all of OXA-48-producing S. marcescens were clonally related, while all eight E. coli and two E. cloacae isolates were clonally unrelated. The predominant clones of carbapenemase-producing K. pneumoniae associated with outbreaks within the hospital were ST147 (n = 13) and ST893 (n = 10). Plasmids carrying blaNDM–1 and blaOXA–48 were successfully transferred to an E. coli K12-recipient strain. The blaOXA–48 gene was located on an IncL/M conjugative plasmid, while the blaNDM–1 gene was located on both IncFII ∼86-kb to ∼140-kb and IncA/C conjugative plasmids. Our findings provide novel epidemiologic data on carbapenemase-producing Enterobacterales (CPE) in Iran and highlight the importance of horizontal gene transfer in the dissemination of blaNDM–1 and blaOXA–48 genes. The occurrence and transmission of distinct K. pneumoniae clones call for improved infection control to prevent further spread of these pathogens in Iran.

Highlights

  • Carbapenems are broad-spectrum beta-lactam agents that are frequently used as a last resort to treat serious infections caused by multidrug-resistant Enterobacterales

  • There is a lot of pilgrimage tourism and business travel between in Tehran (Iran) and neighboring countries such as Iraq, Afghanistan, Pakistan, Turkey, and the Persian Gulf, so travelers with Carbapenemase-producing Enterobacterales (CPE) colonization may be the vectors for spread of resistant strains

  • Initial screening for the presence of carbapenemases was done by the modified Hodge test (MHT) test by following the Clinical and Laboratory Standards Institute [CLSI] (2017) guideline

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Summary

Introduction

Carbapenemase-producing Enterobacterales (CPE) are increasingly reported and represent a major public health threat (Tängdén and Giske, 2015). The most clinically significant carbapenemases in Enterobacterales include the class A (KPC type), class B (metallo-β-lactamases [MBLs] [i.e., VIM, IMP, and NDM types]), and class D carbapenemhydrolyzing β-lactamases (OXA-48-like enzymes) (Nordmann et al, 2011; Tängdén and Giske, 2015). In the scope of outbreaks in Iran, diverse sequence types (STs) of dominant OXA-48- and NDM-producing Klebsiella pneumoniae have been identified in outbreaks or solitary case reports (STs 11, 893, 147, and 915) (Solgi et al, 2017a, 2018). VIM-2-producing K. pneumoniae ST23 has been reported in Iran more recently (Mohammad Ali Tabrizi et al, 2018)

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