Vendrik Karuna E W, de Haan Angela, Witteveen Sandra, Hendrickx Antoni P A, Landman Fabian, Notermans Daan W, Bijkerk Paul, Schoffelen Annelot F, de Greeff Sabine C, Wielders Cornelia C H, Goeman Jelle J, Kuijper Ed J, Schouls Leo M
Centre for Infectious Disease Control, National Institute for Public Health and the Environment (Rijksinstituut voor Volksgezondheid en Milieu, RIVM), Bilthoven, The Netherlands.
Department of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands.
Commun Med (Lond). 2022 May 20;2:55. doi: 10.1038/s43856-022-00115-6. eCollection 2022.
Colistin is a last-resort treatment option for infections with multidrug-resistant Gram-negative bacteria. However, colistin resistance is increasing.
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 or (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 genes. To identify chromosomal mutations potentially leading to colistin resistance, NGS reads were mapped against gene sequences of and .
In total, 72 COLR-EK/COLS-EK pairs (75% and 25% ) were included. Twenty-one percent of COLR-EK patients had received colistin, in contrast to 3% of COLS-EK patients (OR > 2.9). Of COLR-EK isolates, five contained and two . One isolate lost 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.
Colistin resistance is present but uncommon in the Netherlands and caused by the gene in a minority of COLR-EK isolates. There is a need for surveillance of colistin resistance using appropriate susceptibility testing methods.
对于多重耐药革兰氏阴性菌感染，多黏菌素是一种最后的治疗选择。然而，多黏菌素耐药性正在增加。
进行了一项为期6个月的前瞻性配对病例对照研究，有22家荷兰实验室及32家相关医院参与。邀请各实验室向参考实验室最多送检5株耐多黏菌素分离株（COLR-EK）和5株对多黏菌素敏感的分离株（COLS-EK），这些菌株在患者位置、来源材料和细菌种类方面进行匹配。收集流行病学/临床数据并纳入分析。使用逻辑回归对COLR-EK/COLS-EK分离株的特征进行比较，并对用于匹配的变量进行校正。通过下一代测序（NGS）对46对ColR-EK/ColS-EK进行全基因组多位点序列分型和耐药基因鉴定，包括基因。为了鉴定可能导致多黏菌素耐药的染色体突变，将NGS读数与和的基因序列进行比对。
总共纳入了72对COLR-EK/COLS-EK（75%和25%）。21%的COLR-EK患者接受过多黏菌素治疗，相比之下，COLS-EK患者中这一比例为3%（比值比>2.9）。在COLR-EK分离株中，5株含有，2株含有。一株分离株在反复传代培养后失去，但仍保留多黏菌素耐药性。在46株测序的COLR-EK分离株中，遗传多样性很大，19株（41.3%）分离株具有可能与多黏菌素耐药相关的染色体突变。
在荷兰存在多黏菌素耐药情况，但并不常见，少数COLR-EK分离株中的耐药是由基因引起的。需要使用适当的药敏试验方法对多黏菌素耐药性进行监测。
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