• Troelstra, Annet
• Nagtegaal-Baerveldt, Karolien
• Dijk, Karin Van
• Kolwijck, Eva
• Koene, Fleur
• Frénay, Ine
• Burgel, Nathalie Van
• Biggelaar, Rik Van Den
• Heemstra, Karen
• Goeman, Jelle J.
• Mens, Suzan Van
• Ott, Alewijn
• Notermans, Daan W.
• Schoffelen, Annelot F.
• Haan, Angela De
• Kuijper, Ed J.
• Muller, Anouk
• Kampinga, Greetje
• Meer, Coby Van Der
• Veen, Annemarie Van T.
• Jager, Steve De
• Bosboom, Ron
• Hira, Vishal
• Consortium, Colre Survey
• Schouls, Leo. M.
• Pontesilli, Oscar
• Vainio, Saara
• Bijllaardt, Wouter Van Den
• Wielders, Lieke
• Hendrickx, Antoni P. A.
• Bijkerk, Paul
• Greeff, Sabine C. De
• Witteveen, Sandra
• Vendrik, Karuna
• Landman, Fabian

Abstract

<jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A six-month prospective matched case-control study was performed in which 22 Dutch laboratories with 32 associated hospitals participated. Laboratories were invited to send a maximum of five colistin-resistant <jats:italic>Escherichia coli</jats:italic> or <jats:italic>Klebsiella pneumoniae</jats:italic> (COLR-EK) isolates and five colistin-susceptible isolates (COLS-EK) to the reference laboratory, matched for patient location, material of origin and bacterial species. Epidemiological/clinical data were collected and included in the analysis. Characteristics of COLR-EK/COLS-EK isolates were compared using logistic regression with correction for variables used for matching. Forty-six ColR-EK/ColS-EK pairs were analysed by next-generation sequencing (NGS) for whole-genome multi-locus sequence typing and identification of resistance genes, including <jats:italic>mcr</jats:italic> genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of <jats:italic>pmrAB, phoPQ, mgrB</jats:italic> and <jats:italic>crrB</jats:italic>.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>In total, 72 COLR-EK/COLS-EK pairs (75% <jats:italic>E. coli</jats:italic> and 25% <jats:italic>K. pneumoniae</jats:italic>) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR &gt; 2.9). Of COLR-EK isolates, five contained <jats:italic>mcr-1</jats:italic> and two <jats:italic>mcr-9</jats:italic>. One isolate lost <jats:italic>mcr-9</jats:italic> after repeated sub-culturing, but retained colistin resistance. Among 46 sequenced COLR-EK isolates, genetic diversity was large and 19 (41.3%) isolates had chromosomal mutations potentially associated with colistin resistance.</jats:p></jats:sec><jats:sec><jats:title>Conclusions</jats:title><jats:p>Colistin resistance is present but uncommon in the Netherlands and caused by the <jats:italic>mcr</jats:italic> gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.</jats:p></jats:sec>

Topics

• impedance spectroscopy
• size-exclusion chromatography
• susceptibility