Two genetically related Klebsiella pneumoniae strains carrying OXA-type carbapenemases were isolated from a single patient 1 month apart. Kpn163 harboured OXA-163 and Kpn247 a new variant named OXA-247 that showed susceptibility to carbapenems and expanded-spectrum cephalosporins similar to OXA-48. Our epidemiological, biochemical and molecular results suggest the intrapatient emergence of blaOXA -247 from blaOXA -163.
dWe assessed a novel immunochromatographic lateral flow assay for direct identification of OXA-48-like carbapenemases and accurate differentiation of allele variants with distinct substrate profiles (OXA-48 or OXA-163 subfamilies). The assay allowed rapid (less than 4 min) and reliable direct confirmation of OXA-163-and/or OXA-48-like enzymes (with 100% sensitivity and 100% specificity) from cultured colonies that were recovered from both solid medium and spiked blood culture bottles. The emergence and spread of Enterobacteriaceae that produce plasmids encoding class A (KPC, GES, Sme, NMC-A), B (IMP, VIM, NDM), and D (OXA-48-like) carbapenemases are worldwide public health threats. To prevent the spread of carbapenemase producers and define an appropriate empirical antimicrobial therapy, the rapid detection of carbapenemase-producing organisms has become imperative (1). One of the major concerns for controlling the spread of OXA-48-like producers is the absence of reliable phenotypical tests that might contribute to their easy recognition. This is due in part to relatively low carbapenem MICs, a lack of suitable inhibitor compounds for use in confirmatory tests, and the very low expression of carbapenemase activity which cannot be detected readily by recently developed biochemical methods (1-5). Recently, a novel means of detecting OXA-48-like enzymes via an antibody-mediated approach was developed (6). The OXA-48 K-SeT test (Coris BioConcept, Belgium) relies on immunological capture of two epitopes specific to the OXA-48 variants OXA-48, OXA-181, OXA-204, OXA-232, and OXA-244 using colloidal gold nanoparticles bound to a nitrocellulose membrane within a lateral flow device (6). The reported sensitivity and specificity were both 100%, with the result obtained in less than 10 min (6-10). Noteworthy is that new allelic variants of OXA-48 have emerged, namely, OXA-163 and the related variants OXA-247, , which are not recognized by the OXA-48 K-SeT test (6,8,10). OXA-163, which is the only variant of this subfamily that has spread to several hospitals in Argentina and Egypt (15, 16), differs from OXA-48 by a single amino acid substitution and a four-amino-acid deletion. In earlier studies, OXA-163 exhibited almost undetectable carbapenemase activity with a substrate profile that included broad-spectrum cephalosporins (11). However, recent reports indicate that this allele might produce enhanced carbapenemase activity in the presence of carbonates (13, 17), suggesting that its activity is strongly influenced by the rate of carboxylation of the active site, as observed for other carbapenem-hydrolyzing class D -lactamases (18,19). Additionally, in vivo data suggested that OXA-163 might cause carbapenem treatment failures in critically ill patients (12,15,20) or favor intrapatient selection of new OXA-48 variants (12), which highlights the urgent need for efficient identification tests.Definitive confirmation of OXA-163-and/or OXA-48-like producers currently relies on molecular assays and gene sequencing for the assign...
In Argentina, NDM metallo-β-lactamase was first reported in 2013. By now, it has disseminated throughout the country in diverse Gram negative bacteria. Here, we report the case of a paediatric patient that underwent a 1-year hospitalisation due to erythrodermic psoriasis in 2014 and received multiple antimicrobial treatments. During his stay, five isolates were obtained from rectal swabs (rs) or blood culture (bc) suspicious of carbapenemase production: a K. quasipneumoniae subsp. quasipneumoniae (rs), Citrobacter freundii (rs), Escherichia coli (bc), Enterobacter cloacae (rs), and a Serratia marcescens (bc). The isolates were studied with broth microdilution, biparental conjugation and plasmid and whole genome sequencing (Illumina). All isolates harboured an 138,998-bp type 1 IncC plasmid that carried blaNDM-1, bleMBL, blaCMY-6, rmtC, aac(6’)-Ib, and sul1 resistance genes. Additionally, the blaNDM-plasmids contained ISKpn8 an insertion sequence previously described as associated only to blaKPC. One isolate, a colistin-resistant E. coli, also carried a mcr-1-containing an IncI2 plasmid, which did not harbour additional resistance. The whole genome of K. quasipneumoniae subsp. quasipneumoniae isolate was fully sequenced. This isolate harboured, additionally to blaNDM, three plasmid-mediated quinolone resistance genes: qnrB4, qnrB52 and aac(6’)-Ib-cr1. The E. cloacae isolate also harboured qnrA1. These findings alert to the underestimated horizontal dissemination of multidrug-resistant plasmids limiting treatment options with last resort antimicrobials.
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