RESIST-5 O.O.K.N.V. and NG-Test Carba 5 assays for the rapid detection of carbapenemase-producing Enterobacterales from positive blood cultures: a comparative study

Bloodstream infection by two subpopulations of Klebsiella pneumoniae ST1685 carrying KPC-33 or KPC-14 following ceftazidime/avibactam treatment: considerations regarding acquired heteroresistance and choice of carbapenemase detection assay

“…As recently shown, KPC-14 and KPC-33 variants exhibit loss of carbapenemase activity and increased affinity to ceftazidime, which prevent avibactam from binding to and inhibiting the enzyme, [7][8][9] in agreement with our findings. In detail, both bla KPC mutations led to loss of meropenem resistance, expression of ESBL phenotype and reduction of ceftazidime/avibactam susceptibility.…”

“…bla KPC genes were investigated by amplification and sequencing. 7 Genetic relatedness of the three strains was determined by MLST and PFGE. Antimicrobial susceptibility was determined by a commercially available microdilution assay (Panel NMDR, Microscan WalkAway 96 Plus, Beckman Coulter, Switzerland) and MIC values of ceftazidime/avibactam were confirmed using the Etest method (bioMérieux, France).…”

Application and clinical impact of the RESIST-4 O.K.N.V. rapid diagnostic test for carbapenemase detection in blood cultures and clinical samples

“…Having originally been designed to detect only one specific type of carbapenemases, the RDT used in this study was adapted several times to accommodate the concurrent detection of KPC and OXA-48 carbapenemases [7], with later addition of NDM [8] and VIM. In the meantime, an updated version was developed and made commercially available, which also includes OXA-163 [9]. Several laboratory assessments have shown excellent sensitivity and specificity, as elucidated by, for example, a detailed validation on clinical samples in the Belgian National Reference Centre for identification of the mechanisms related to carbapenem resistance [5].…”

“…With regard to positive blood culture bottles, a proof-ofprinciple study conducted on the previous version of this RDT (RESIST-3) showed a sensitivity and specificity of 100%, respectively, for carbapenemase detection if blood cultures were spiked in the laboratory with carbapenemase-producing bacteria and the test applied on a centrifuged lysate of positive blood cultures [15]. Of note, an additional evaluation from Italy on spiked blood cultures elucidated that a newer version of the RDT (RESIST-5) failed to detect KPC variants with a D179Y point mutation and observed a lower sensitivity for detection of VIM and NDM on blood culture pellets [9], which is in line with findings from a previous study [16]. The D179Y point mutation may confer resistance to ceftazidime-avibactam [17].…”

Meropenem/vaborbactam-based combinations against KPC-producing Klebsiella pneumoniae and multidrug-resistant Pseudomonas aeruginosa

“…The bla KPC genes of the KPC-Kp isolates were previously characterised by PCR and DNA sequencing [5] . The 13 KPC-Kp isolates harboured bla KPC-3 ( n = 5), bla KPC-2 ( n = 4), bla KPC-31 ( n = 2), bla KPC-33 ( n = 1) and bla KPC-14 ( n = 1).…”