Potential impact of antimalarial chemoprophylaxis with doxycycline on antimicrobial resistance genes in the enteric microbiome of deployed German soldiers – a case-control-study

Antimalarial chemoprophylaxis with doxycycline is taken by German soldiers on tropical deployments. In a case-control-assessment, diagnostic metagenomics was applied to comparatively assess antimicrobial resistance genes in enteric microbiomes of soldiers with and without medical history of doxycycline-based antimalarial chemoprophylaxis on deployment. Two groups of 26 military deployment returnees, each either exposed or non-exposed to antimalarial chemoprophylaxis with doxycycline, were matched by deployment site and period, age and sex in declining order of prioritization. Metagenomic analysis of stool samples was applied to detect resistance gene sequences within the sample materials. In total, 3,770 different antibiotic resistance genes were detected across all samples. No significant differences were found in the frequency of antibiotic resistance genes in each sample compared between the doxycycline group and the control group. Approximately one third of metagenomically assembled genomes could be identified taxonomically at the species level (32.2%) and over half at the genus level (53.9%). The overall distribution of ABR genes at the species level showed that Escherichia coli was host for over a quarter of detected genes – 1,021 genes in only 42 identified genomes. Hosts with the next highest number of ABR genes were Escherichia marmotae (156 genes), Staphylococcus aureus (85 genes), Klebsiella michiganensis (63 genes) and Leclercia adecarboxylata (62 genes). The study suggests – if any – only a low impact of doxycycline intake during military deployments on the enteric resistome of soldiers at post-deployment assessments. Reasons for Escherichia ’s high ABR gene load remain to be investigated.