Author Correction: Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Global phylogenetic analysis of Escherichia coli and plasmids carrying the mcr-1 gene indicates bacterial diversity but plasmid restriction.

To understand the dynamics behind the worldwide spread of the mcr-1 gene, we determined the population structure of Escherichia coli and of mobile genetic elements (MGEs) carrying the mcr-1 gene. After a systematic review of the literature we included 65 E. coli whole genome sequences (WGS), adding 6 recently sequenced travel related isolates, and 312 MLST profiles. We included 219 MGEs described in 7 Enterobacteriaceae species isolated from human, animal and environmental samples. Despite a high overall diversity, 2 lineages were observed in the E. coli population that may function as reservoirs of the mcr-1 gene, the largest of which was linked to ST10, a sequence type known for its ubiquity in human faecal samples and in food samples. No genotypic clustering by geographical origin or isolation source was observed. Amongst a total of 13 plasmid incompatibility types, the IncI2, IncX4 and IncHI2 plasmids accounted for more than 90% of MGEs carrying the mcr-1 gene. We observed significant geographical clustering with regional spread of IncHI2 plasmids in Europe and IncI2 in Asia. These findings point towards promiscuous spread of the mcr-1 gene by efficient horizontal gene transfer dominated by a limited number of plasmid incompatibility types.

Travel-related acquisition of diarrhoeagenic bacteria, enteral viruses and parasites in a prospective cohort of 98 Dutch travellers.

BACKGROUND: Limited prospective data are available on the acquisition of viral, bacterial and parasitic diarrhoeagenic agents by healthy individuals during travel. METHODS: To determine the frequency of travel associated acquisition of 19 pathogens in 98 intercontinental travellers, qPCR was used to detect 8 viral pathogens, 6 bacterial enteric pathogens and 5 parasite species in faecal samples collected immediately before and after travel. RESULTS: We found high pre-travel carriage rates of Blastocystis spp. and Dientamoeba fragilis of 32% and 19% respectively. Pre-travel prevalences of all other tested pathogens were below 3%. Blastocystis spp. (10%), Plesiomonas shigelloides (7%), D. fragilis (6%) and Shigella spp. (5%) were the most frequently acquired pathogens and acquisition of enteral viruses and hepatitis E virus in this relatively small group of travellers was rare or non-existent. CONCLUSIONS: Our findings suggest that the role of viruses as the cause of persisting traveller's diarrhoea is limited and bacterial pathogens are more likely as a cause of traveller's diarrhoea. The substantial proportion of travellers carrying Blastocystis spp. and D. fragilis before travel warrants cautious interpretation of positive samples in returning travellers with gastrointestinal complaints.

Import and spread of extended-spectrum ß-lactamase-producing Enterobacteriaceae by international travellers (COMBAT study): a prospective, multicentre cohort study.

BACKGROUND: International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation, and probability of onward transmission. METHODS: Within the prospective, multicentre COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behaviour were collected before travel and immediately and 1, 3, 6, and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded ß-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 was used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. This study is registered with ClinicalTrials.gov, number NCT01676974. FINDINGS: 633 (34·3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32·1-36·5), with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75·1%, 95% CI 68·4-80·9). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2·69, 95% CI 1·79-4·05), traveller's diarrhoea that persisted after return (2·31, 1·42-3·76), and pre-existing chronic bowel disease (2·10, 1·13-3·90). The median duration of colonisation after travel was 30 days (95% CI 29-33). 65 (11·3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days, 95% CI 48-102, p=0·0001). Onward transmission was found in 13 (7·7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5-18). INTERPRETATION: Acquisition and spread of ESBL-E during and after international travel was substantial and worrisome. Travellers to areas with a high risk of ESBL-E acquisition should be viewed as potential carriers of ESBL-E for up to 12 months after return. FUNDING: Netherlands Organisation for Health Research and Development (ZonMw).

Prolonged carriage and potential onward transmission of carbapenemase-producing Enterobacteriaceae in Dutch travelers.

AIM: The aim was to study acquisition and persistence of carbapenemase-producing Enterobacteriaceae (CPE) among travelers. MATERIALS & METHODS: Stools from 2001 travelers and 215 nontraveling household members, collected before and immediately post-travel as well as 1, 3, 6 and 12 months upon return, were screened for CPE. RESULTS: Five travelers, all visiting Asia outside the Indian subcontinent, acquired CPE. One traveler persistently carried the same OXA-244 CPE up to 6 months post-travel. Three months after travel, her co-traveling spouse also became positive for this OXA-244 CPE strain, suggesting clonal transmission within this household. CONCLUSION: Acquisition of CPE is not restricted to travelers to the Indian subcontinent and/or to travelers seeking healthcare during travel and can persist up to at least 6 months post-travel.

Salmonella subtypes with increased MICs for azithromycin in travelers returned to The Netherlands.

Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999-2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.

Is paromomycin the drug of choice for eradication of Blastocystis in adults?

Blastocystis is a protozoan parasite of controversial clinical significance that is often detected in stools of patients with gastrointestinal complaints. Patients infected with Blastocystis and persistent, unexplained gastrointestinal complaints are often treated with the intention to eradicate Blastocystis. However, there is no consensus on the most effective drug. We performed a retrospective follow-up study with a large cohort of patients in which the natural disease course and efficacy of treatment with either paromomycin, clioquinol, or metronidazole were evaluated. With an eradication rate of 77 %, treatment with paromomycin appeared significantly more effective than treatment with clioquinol (38 %), metronidazole (38 %), or no treatment (22 %). This study showed that (1) Blastocystis was frequently observed in the stools of our patient group (34 %), (2) spontaneous clearance of Blastocystis infections occurred only in a small proportion of patients (22 %), and therefore (3) drug treatment is required for more efficient eradication of Blastocystis. Paromomycin exhibited superior performance in comparison to both metronidazole and clioquinol.

Is paromomycin the drug of choice for eradication of Dientamoeba fragilis in adults?

Dientamoeba fragilis is a debated protozoan parasite that is often detected in stools of patients with chronic gastro-intestinal complaints. A retrospective follow-up study of a large cohort of patients was performed to better understand the natural course of the infection and possible treatment options. D. fragilis was spontaneously cleared in 41% of untreated cases. With an eradication rate of 98%, treatment with paromomycin appeared more effective than treatment with clioquinol (83%) or metronidazole (57%).