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Background  Treatment of pandrug-resistant isolates often necessitates combination therapy. Checkerboard synergy and time-killing assay tests were performed to evaluate the benefits of a triple combination with meropenem, ertapenem, and colistin against 10 colistin-resistant  K. pneumoniae  clinical isolates harboring different β-lactamases. (bla OXA-48 , bla NDM ).    Materials and methods  In this study, ertapenem and meropenem (ERT/MEM), meropenem and colistin (MEM/COL), ertapenem, meropenem and colistin (ERT/MEM/COL) combinations were tested using checkerboard techniques and time-kill assays of each antibiotic alone and in combination against 10 colistin-resistant clinical  K. pneumoniae  isolates. An analysis of  K. pneumoniae  isolate B6 using a scanning electron microscope revealed morphologic changes in the cell surface after treatment with each antibiotic both alone and in combination. The whole genome of  K. pneumoniae  KPNB1 was sequenced using an Ion Torrent PGM sequencer.    Results  According to the checkboard results, synergistic combinations were observed with ertapenem/meropenem (5/10 isolates), meropenem/colistin (7/10) and ertapenem/meropenem/colistin (9/10); no antagonism was observed for all combinations. For the time-kill assay results; synergism and bactericidal effects were observed with meropenem/colistin (10/10) and with ertapenem/meropenem/colistin (10/10) combinations, and an indifference effect was observed with the ertapenem and meropenem (10/10) combination. Strain number 1 was found 100% identical to  Klebsiella pneumoniae subsp. pneumoniae  HS11286 according to the outcomes of complete genome sequence analysis, and the strain carried the genes bla OXA-181 , bla CTXM-15 , blaNDM,  arr-3, aac (6′)-Ib-cr, rmtF , and  catB1.Conclusion  Using double carbapenem antibiotics with colistin could be a potential alternative to treat colistin and carbapenem-resistant  K. pneumoniae . The present study is the first Turkish report of OXA–181-type carbapenemase causing colistin resistance.

antimicrobial resistance and infection control

In vitro evaluation of double carbapenem and colistin combinations against OXA-48, NDM carbapenemase-producing colistin-resistant Klebsiella pneumoniae strains