Prolonged carriage of OXA-244-carbapenemase-producing Escherichia coli complicates epidemiological investigations

Abstract

The rapid increase of OXA-244-producing Escherichia coli, predominantly driven by genetically clustered isolates of sequence type (ST)38, has been observed in at least nine European countries, including Germany. However, the reasons for the spread of OXA-244-producing E. coli remain unclear. Here, we aim to evaluate the possibility of prolonged carriage. We identified a total of six different patients with repeated detection of OXA-244-producing E. coli isolates, which were subjected to both short and long-read whole-genome sequencing (WGS). Besides allelic differences using core genome multilocus sequence typing (cgMLST) analyses, we obtained numbers of single-nucleotide polymorphisms (SNPs) to calculate individual base-pair substitution (BPS) rates. To assess possible re-exposure and risk factors for prolonged carriage, case interviews were conducted. The time between detections ranged from eleven months to more than three years. Initial isolates originated in 3/6 cases from clinical samples, remaining samples from screening, mostly in the inpatient setting. As expected, cgMLST analyses showed low numbers of allelic differences between isolates of each case ranging from 1 to 4, whereas numbers of SNPs were between 2 and 99 (mean = 36), thus clearly highlighting the discrepancy between these different bacterial typing approaches. For five out of six cases, observed BPS rates suggest that patients can be colonized with OXA-244-producing E. coli, including ST38 cluster isolates, for extensively long times. Thus, we may have previously missed the epidemiological link between cases because exposure to OXA-244-producing E. coli could have occurred in a time frame, which has not been evaluated in previous investigations. Our results may help to guide future epidemiological investigations as well as to support the interpretation of genetic diversity of OXA-244-producing E. coli, particularly among ST38 cluster isolates.