Importance:Palmoplantar pustulosis (PPP) and palmoplantar plaque psoriasis with pustules remain challenging to treat. Studies suggest that an interleukin 17 or interleukin 36 loop acts synergistically in these diseases to induce palmoplantar pustules. Objective:To assess the effectiveness of bimekizumab in treating PPP and palmoplantar plaque psoriasis with pustules. Design, Setting, and Participants:This case series involved 21 adults with PPP (11 patients) or palmoplantar plaque psoriasis with pustules (10 patients) treated at 1 of 7 tertiary dermatological centers in France from September 2022 through June 2023. All patients treated with bimekizumab for at least 3 months were included in the analyses. Main Outcomes and Measures:The main outcome was the posttreatment Investigator Global Assessment (IGA), scored as 0 (complete clearance), 1 (almost clear), 2 (mild), 3 (moderate), or 4 (severe). When relevant, evolution of joint pain and nail involvement was reported. Tolerance and potential adverse events were noted. Results:A total of 21 patients (mean [range] age, 46 [24-68] years; 19 females) were included. Eleven patients had isolated PPP, and 10 had palmoplantar plaque psoriasis with pustules. All of them, except 2 who received bimekizumab as first systemic therapy, had not responded to at least 1 systemic treatment (median [range], 3 [1-7] treatments), and/or had adverse events leading to the discontinuation of the treatment. Complete clearance (IGA score, 0) was achieved by 17 patients in 1 to 4 months. Three patients achieved an IGA score of 1, and 1 achieved an IGA score of 2. Three patients with PPP also presented with acrodermatitis continua of Hallopeau. Nail involvement showed 50% to 70% improvement after 4 to 6 months of bimekizumab treatment for these 3 patients. Two patients had SAPHO (synovitis, acne, pustulosis, hyperostosis, osteitis) syndrome; both had complete clearance of skin lesions associated with joint pain improvement. Four patients (19%) with candidiasis were successfully treated with oral antifungal agents. None of the patients had to stop bimekizumab treatment due to adverse events. Conclusions and Relevance:The findings of this case series suggest that bimekizumab could be an appealing approach for treating PPP, palmoplantar plaque psoriasis with pustules, and SAPHO syndrome. Prospective randomized placebo-controlled clinical trials are needed to confirm these encouraging initial results.

Smoking-related diseases remain a significant public health concern, and heated tobacco products (HTPs) have emerged as a potential alternative to cigarettes. While several studies have confirmed that HTP aerosols contain lower levels of harmful and potentially harmful constituents (HPHCs) than cigarette smoke, less is known about constituents that are intrinsically higher in HTP aerosols. This study provides a comprehensive comparative assessment of an HTP aerosol produced with Tobacco Heating System 2.2 (THS) and comparator cigarette (CC) smoke aiming at identifying all unique or increased compounds in THS aerosol by applying a broad set of LC–MS and GC × GC–MS methods. To focus on differences due to heating versus burning tobacco, confounding factors were minimized by using the same tobacco in both test items and not adding flavorants. Of all analytical features, only 3.5%—corresponding to 31 distinctive compounds—were significantly more abundant in THS aerosol than in CC smoke. A notable subset of these compounds was identified as reaction products of glycerol. The only compound unique to THS aerosol was traced back to its presence in a non-tobacco material in the test item and not a direct product of heating tobacco. Our results demonstrate that heating a glycerol-containing tobacco substrate to the temperatures applied in THS does not introduce new compounds in the resulting aerosol compared to CC smoke which are detectable with the method portfolio applied in this study. Overall, this study contributes to a better understanding of the chemical composition of HTP aerosols and their potential impact on human health. Graphical Abstract

Psoriasis is a multifactorial skin pathology resulting from genetic susceptibility and environmental triggers that lead to epidermal and immune dysfunction. There is now strong evidence that non-lesional (NL) psoriatic skin, despite its normal appearance, represents an intermediate state between healthy and lesional skin. Changes observed in NL skin mainly affect the skin barrier, keratinocytes, innate and adaptive immune responses, the microbiota and neurogenic tissue innervation. Several epidermal barrier defects are commonly observed in NL skin compared to healthy skin, including an elevated pH, delayed barrier function repair after injury and lower expression of epidermal differentiation complex proteins. NL keratinocytes also show a predisposition for activation and proliferation, and an increased sensitivity to cytokine or microbial triggers, probably linked to their unique transcriptome and proteome, associated with their intermediate state between healthy and lesional cells. In addition, the accumulation of pathogenic IL-17-producing resident memory T cells, which can (re)instigate the formation of new lesions, characterises both the NL and never-lesional skin of patients with psoriasis. Although the contribution of NL skin dysbiosis to psoriasis pathophysiology remains to be clarified, the expression of numerous pruritogenic mediators appears to be involved in disease progression due to an iterative itch-scratch cycle. In summary, the NL skin of patients with psoriasis exhibits numerous hallmarks of dormant psoriasis. The fact that these alterations are mostly located in the epidermis suggests that they are readily accessible to topical treatments, which could prevent the recurrence/spread of this chronic disease.

Le méthotrexate (MTX) est une option thérapeutique hors AMM dans la dermatite atopique (DA) modérée à sévère lorsque les traitements locaux sont insuffisants. Notre objectif était d'identifier des facteurs prédictifs de bonne ou mauvaise réponse au MTX dans la DA. Une étude rétrospective impliquant 9 centres du GREAT a inclus des adultes atteints de DA modérée à sévère. Des caractéristiques cliniques et biologiques ont été recueillies afin d'évaluer l'efficacité, la tolérance et la durée de maintien du MTX. Les facteurs prédictifs de réponse au MTX ont été recherchés par des analyses uni- et multivariées, en comparant la réponse au MTX dans différentes sous-populations de patients. La réponse au MTX était définie par une diminution de plus de 50 % du SCORAD (SCORing Atopic Dermatitis) ou l'obtention d'un score IGA (Investigator Global Assessment) à 0 ou 1 ou une baisse de 2 points ou plus, à 3, 6 ou 12 mois de traitement, par rapport à l'initiation du MTX. Un total de 272 patients ont été inclus. Les patients étaient considérés comme répondeurs au MTX dans 41 % (83/203), 59 % (93/158) et 79 % (86/109) des cas à 3, 6 et 12 mois respectivement. Des effets indésirables étaient rapportés dans 39 % (106/272) des cas, avec principalement 22 % (59/272) d'intolérances digestives et 14 % (37/272) d'anomalies biologiques. La survie médiane du traitement par MTX était de 23 mois, bien supérieure chez les répondeurs (36 mois) que chez les non répondeurs où le MTX était interrompu après 6 mois de traitement en moyenne. Les principales causes d'arrêt étaient les effets secondaires (40 %, 61/152), l'inefficacité (28 %, 42/152) et la perte d'efficacité (17 %, 26/152). Les facteurs de bonne réponse au MTX étaient un score IGA à 4 (très sévère) (p < 0,03) et une éosinophilie > 0,5 G/L (p < 0,04) à l'initiation du traitement. Un tabagisme actif était un facteur de mauvaise réponse au traitement (p < 0,07). Le MTX est utilisé de longue date dans le traitement de la DA. Plusieurs études attestant de son efficacité et de sa bonne tolérance, mais peu incitent à une prescription plus personnalisée dans la DA l'évaluation de la sévérité initiale de la DA, la recherche d'un tabagisme actif, d'une éosinophilie sanguine semblent utiles pour guider le clinicien dans son choix thérapeutique.

741 comparable to control, indicating a lack of effect on Mycobacterium tuberculosis dormancy [5]. Indeed, both clinical trial and real-world data show that IL-17 inhibitors are not associated with an increased incidence of TB infection or reactivation [1]. Based on an assessment of secukinumab safety in five clinical trials, involving 132 subjects with a history of treated pulmonary tuberculosis, 25 individuals who tested negative based on an interferon gamma release assay (IGRA) demonstrated no reactivation of LTBI and received no anti-TB medication, whereas 107 subjects who tested positive for LTBI received anti-TB medication [6]. Additionally, 12 real-world patients with psoriasis who were found to have LTBI received secukinumab without previous chemoprophylaxis and none of them showed tuberculosis reactivation [7]. Based on a post-hoc analysis of 11 Phase I-III ixekizumab (anti IL17A) clinical trials, including 5,730 patients, some with a history of treated active TB or newly diagnosed LTBI, 72 patients developed treatment-emergent LTBI or positive IGRA/TST results; 14 patients diagnosed after 52 weeks continued with ixekizumab treatment and no patients developed active TB during observation [8]. Data for brodalumab, an IL-17R inhibitor, is still limited. For IL-23 inhibitors, although evidence is still scarce, available data suggests that there is no increased risk of TB reactivation with IL-23 inhibitors [3]. Of the 31 subjects from the IMMHANCE study with LTBI who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on risankizumab [9]. Concerning guselkumab, using pooled safety data up to Week 100 of VOYAGE 1&2, no cases of LTBI reactivation were noted [10]. Altogether, it may be reasonable to assume that IL-17 and IL-23 inhibitors do not increase the risk of TB reactivation. The two cases presented here were investigated in daily clinical practice, where LTBI treatment was not feasible and the use of secukinumab was revealed to be safe. Although LTBI should remain a concern when using biologics in patients with psoriasis, in selected cases, IL-17 and IL-23 inhibitors may represent a safe treatment option.

Background: Yellow fever vaccine (YFV) is not advised for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. Objective: To assess the risk of relapsing-remitting multiple sclerosis (RR-MS) worsening after YFV. Methods: Non-interventional observational retrospective, exposed/non-exposed cohort study nested in the French national cohort including MS. Results: 128 RR-MS were included. The 1-year annualized relapse rate (ARR) following YFV did not differ between exposed: 0.219 (0.420) and non-exposed subjects: 0.208 (0.521) (p = 0.92). Time to first relapse was not different between groups (adjusted hazard ratio (HR) = 1.33; 95% confidence interval (CI) = 0.53–3.30, p = 0.54). Conclusion: These results suggest that YFV does not worsen the course of RR-MS.

Summary In order to assess robustness for the reduction of harmful and potentially harmful constituent (HPHC) levels generated by the Tobacco Heating System 2.2 (THS 2.2), a heated tobacco product, we compared the aerosol of this product with mainstream smoke from the 3R4F reference cigarette under different conditions of temperature and humidity. The desired climatic conditions were achieved by using an air-conditioning system coupled with the smoking-machine housing. Two extreme climatic conditions were selected, representing a “Hot and Dry” climate (30 °C and 35% relative humidity RH) and a “Hot and Very Humid” climate (30 °C and 75% RH). In addition, aerosol and smoke were generated using the standard conditions recognized for smoking-machine analyses of tobacco products (22 °C and 60% RH), which were close to the climatic conditions defined for “Subtropical and Mediterranean” environments (25 °C and 60% RH). The experimental conditions were chosen to simulate the use of THS 2.2 and cigarettes under extreme conditions of temperature and humidity. HeatSticks and cigarettes taken from freshly opened packs were subjected to short-term conditioning from two to a few more days under the same experimental conditions. We analyzed 54 HPHCs in THS 2.2 aerosol and 3R4F cigarette smoke, generated in accordance with the Health Canada Intense (HCI) standard, using modified temperature and humidity conditions for sample conditioning and machine-smoking experiments. We used a volume-adjusted approach for comparing HPHC reductions across the different climatic conditions investigated. Although a single puffing regimen was used, the total puff volume recorded for the 3R4F cigarette smoke varied due to the influence of temperature and humidity on combustion rate, which justified the use of a volume-adjusted approach. Volume-adjusted yields were derived from HPHC yields expressed in mass-per-tobacco stick normalized per total puff volume. The results indicated that, regardless of the considered climatic conditions, the HPHC levels investigated in THS 2.2 aerosol were reduced by at least 90%, on average, when compared with the concentrations in 3R4F cigarette mainstream smoke. This confirmed the robustness in performance for THS 2.2 to deliver reduced levels of HPHCs under the extreme climatic conditions investigated in this study. In order to further characterize the robustness of these reductions, the lowest reduction performance achieved for individual HPHCs across all climatic conditions was used to define the threshold for a robust reduction. The majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. Calculations derived from nicotine-adjusted yields also confirmed robust reductions for all investigated HPHCs. The small differences in absolute reduction between the volume- and nicotine-adjusted approaches were predominantly attributed to a combination of the differences in both nominal nicotine deliveries and total puff volumes between THS 2.2 and 3R4F cigarettes; however, this did not influence the determination of robustness. Our findings confirm the value of this approach for assessing the robustness of a product’s performance under different climatic conditions.

Background: Psoriasis is a chronic inflammatory skin disease that has a profound effect on health-related quality of life (HRQoL). Patient education programmes may help patients to gain life-long control over their chronic disease. Objective: This multicentre randomised controlled study evaluated whether a standardised multidisciplinary education programme was beneficial to psoriasis patients. Methods: Adults with moderate-to-severe psoriasis were randomly assigned (1:1) to an intervention group to receive an educational programme or to a control group to receive usual care. Randomization was stratified by previous treatment history. The primary outcome was HRQoL, assessed by scoring the Skindex-29 domains emotion, symptom, and functioning. Psoriasis severity was assessed using the psoriasis area severity index (PASI). Levels of perceived stress, patient knowledge about psoriasis, and patient satisfaction were also assessed. Follow-up evaluations were performed at 3, 6, and 12 months. Results: A total 142 patients formed the intention-to-treat population: 70 in the control group and 72 in the intervention group. Skindex component scores and the PASI were significantly lower at 3, 6, and 12 months as compared to baseline in both groups, but no significant differences were found between the groups. Knowledge about psoriasis improved significantly during follow-up amongst patients from the intervention group compared to controls (68% of correct answers vs. 56%; p < 0.01). Patient satisfaction with psoriasis management and treatment was also better in the intervention group. Conclusions: The standardised education programme did not improve HRQoL and disease severity in psoriasis, but led to a significant improvement in patient knowledge about the disease and increased patient satisfaction.

Summary In the absence of standards specific for testing the reduction robustness of the levels of harmful and potentially harmful constituents (HPHCs), the aerosol from the THS 2.2, a heated tobacco product, was compared with the mainstream smoke of the 3R4F reference cigarette over a broad range of machine-smoking regimes. The average reduction and the introduced concept of threshold limits of robust reduction were derived from HPHC concentrations, in mass per tobacco-stick normalized per total puff volume, to propose an alternative for the assessment of products where nicotine-adjusted yields would be inappropriate. In addition, this study explores the influence of 3R4F reference cigarette filter ventilation, and discusses the roles of temperature and precursors in the present context of robustness of HPHC reduction. Fifty-four HPHCs were analyzed under multiple regimes in THS 2.2 aerosol and 3R4F cigarette smoke. The average reduction of HPHC concentrations compared across all regimes characterized the robustness. Threshold limits of reduction of individual HPHCs were statistically determined across all regimes. The results observed under Health Canada Intense (HCI) and more intense regimes indicated that on average the reductions in HPHCs levels investigated in THS 2.2 aerosol were more than 90% and that the majority of the 54 HPHCs investigated in THS 2.2 aerosol showed more than 90% reduction. The robustness of THS 2.2 in maintaining the levels of reduction of representative HPHCs, whatever the puffing regime, can be quantified. The mass of HPHC per tobacco-stick normalized per total puff volume is a valuable approach to compare the robustness of the performance of a product over a large range of puffing conditions. Our findings will greatly complement the assessment for robustness of current and future similar products where classical approaches would present limitations.

The risk of acquisition of multidrug-resistant Enterobacteriaceae (MRE) and of occurrence of diarrhea is high when traveling to tropical regions. The relationships between these phenomena and the composition of human gut microbiota have not yet been assessed. Here, we investigated the dynamics of changes of metabolically active microbiota by sequencing total RNA from fecal samples taken before and after travel to tropical regions. We included 43 subjects who could provide fecal samples before and after a travel to tropical regions. When found positive by culturing for any MRE after travel, the subjects sent an additional sample 1 month later. In all, 104 fecal samples were considered (43 before travel, 43 at return, 18 one month after travel). We extracted the whole RNA, performed retrotranscription and sequenced the cDNA (MiSeq 2x300bp). The reads were mapped to the reference operational taxonomic units (OTUs) and species/strains using the 16S Greengenes and 23S SILVA databases. We found that the occurrence of diarrhea during the travel was associated with a higher relative abundance of Prevotella copri before departure and after return. The composition of microbiota, before travel as well as at return, was not correlated with the acquisition of MRE. However, the clearance of MRE one month after return was linked to a specific pattern of bacterial species that was also found before and after return. In conclusion, we found specific OTUs associated to a higher risk of diarrhea during a stay in tropical regions and to a faster clearance of MRE after their acquisition.

BACKGROUND: Methotrexate is currently used to treat atopic dermatitis but has never been assessed versus cyclosporine in adults. OBJECTIVE: This study evaluated the efficacy and safety of methotrexate versus cyclosporine in patients with moderate-to-severe atopic dermatitis. METHODS: Patients were randomized to receive either oral methotrexate (15 mg/wk) or cyclosporine (2.5 mg/kg/d) for 8 weeks. The primary end point was a patient achieving 50% improvement in the SCORing Atopic Dermatitis index (SCORAD 50) at week 8. When the primary end point was not achieved, methotrexate was increased to 25 mg and cyclosporine to 5 mg during the next 16 weeks. The secondary end points were a patient achieving a 50% reduction in the Eczema Area Severity Intensity index (EASI 50) and SCORAD 50 at each visit (ClinicalTrials. gov no. NCT00809172). RESULTS: A total of 97 patients received methotrexate 15 mg (n = 50) or cyclosporine 2.5 mg (n = 47). Regarding the primary end point at week 8, methotrexate was inferior to cyclosporine because the proportion of patients with SCORAD 50 was 8% (4 of 50) in the methotrexate arm versus 42% (18 of 43) in the cyclosporine arm. The difference in percentages for the 2 treatment groups (2-sided 90% CI) was -34% (-48% to -20%). At week 8, methotrexate and cyclosporine dosages were increased in 56% and 49% of the patients, respectively. Regarding EASI 50, the noninferiority end point was reached at week 20 in 92% (22 of 24) of patients in the methotrexate arm and 87% (26 of 30) of patients in the cyclosporine arm. The treatment-related adverse events were more frequent with cyclosporine (P <.0001). CONCLUSIONS: Methotrexate 15 mg/wk was inferior to cyclosporine 2.5 mg/kg/d at week 8. Increasing the doses of methotrexate to 25 mg/wk induced a significant improvement versus cyclosporine at week 20. (C) 2017 American Academy of Allergy, Asthma & Immunology

Background Measles virus (MV) infection is marked with a skin rash in the acute phase of the disease, which pathogenesis remains poorly understood. Moreover, the association between measles and progression of skin diseases, such as atopic dermatitis (AD), is still elusive. Objective We have thus analysed the susceptibility of human keratinocytes to MV infection and explore the potential relationship between MV vaccination and the pathogenesis the AD. Methods We performed immunovirological characterisation of MV infection in human keratinocytes and then tested the effect of live attenuated measles vaccine on the progression of AD in adult patients, in a prospective, double-blind study. Results We showed that both human primary keratinocytes and the keratinocyte cell line HaCaT express MV receptors and could be infected by MV. The infection significantly modulated the expression of several keratinocyte-produced cytokines, known to be implicated in the pathogenesis of inflammatory allergic diseases, including AD. We then analysed the relationship between exposure to MV by vaccination and the progression of AD in 20 adults during six weeks. We found a significant decrease in CCL26 and thymic stromal lymphopoietin (TSLP) mRNA in biopsies from acute lesions of vaccinated patients, suggesting MV-induced modulation of skin cytokine expression. Clinical analysis revealed a transient improvement of SCORAD index in vaccinated compared to placebo-treated patients, two weeks after vaccination. Conclusions Altogether, these results clearly demonstrate that keratinocytes are susceptible to MV infection, which could consequently modulate their cytokine production, resulting with a beneficial effect in the progression of AD. This study provides thus a proof of concept for the vaccination therapy in AD and may open new avenues for the development of novel strategies in the treatment of this allergic disease.

Atopic dermatitis (AD) is a common skin inflammatory disease characterized by the production of thymic stromal lymphopoietin (TSLP) and marked TH 2 polarization. Recent studies suggest that IL-1β contributes to the development of AD skin inflammation. Here, we have investigated the impact of IL-1β signalling on the epidermal homeostasis of both healthy subjects and AD patients [with functional filaggrin (FLG) alleles], with particular attention to TSLP production and keratinocyte differentiation. In healthy reconstructed human epidermis (RHE), IL-1β promoted (i) robust secretion of TSLP in an NF-κB-dependent manner and (ii) a significant decrease in the expression of filaggrin and other proteins of the epidermal differentiation complex. These effects were prevented by treatment of RHE with the anti-IL-1β mAb canakinumab and by the IL-1 receptor antagonist anakinra. Interestingly, RHE generated from AD donors behaved like that of healthy individuals and showed comparable responses to IL-1β signals. Collectively, our results suggest that IL-1β may be an early key mediator for the acquisition of an AD phenotype through induction of TSLP and alteration of the epidermal homeostasis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

For administration of multiple live attenuated vaccines, the Advisory Committee on Immunization Practices recommends either simultaneous immunization or period of at least 28 days between vaccines, due to a possible reduction in the immune response to either vaccine. The main objective of this study was to compare the immune response to measles (alone or combined with mumps and rubella) and yellow fever vaccines among infants aged 6-24 months living in a yellow fever non-endemic country who had received measles and yellow fever vaccines before travelling to a yellow fever endemic area. Subjects and methods: A retrospective, multicenter case-control study was carried out in 7 travel clinics in the Paris area from February 1st 2011 to march 31,2015. Cases were defined as infants immunized with the yellow fever vaccine and with the measles vaccine, either alone or in combination with mumps and rubella vaccine, with a period of 1-27 days between each immunization. For each case, two controls were matched based on sex and age: a first control group (control 1) was defined as infants having received the measles vaccine and the yellow fever vaccine simultaneously; a second control group (control 2) was defined as infants who had a period of more than 27 days between receiving the measles vaccine and yellow fever vaccine. The primary endpoint of the study was the percentage of infants with protective immunity against yellow fever, measured by the titer of neutralizing antibodies in a venous blood sample. Results: One hundred and thirty-one infants were included in the study (62 cases, 50 infants in control I and 19 infants in control 2). Of these, 127 (96%) were shown to have a protective titer of yellow fever antibodies. All 4 infants without a protective titer of yellow fever antibodies were part of control group 1. Discussion: The measles vaccine, alone or combined with mumps and rubella vaccines, appears to have no influence on humoral immune response to the yellow fever vaccine when administered between 1 and 27 days. The absence of protective antibodies against yellow fever was observed only among infants who received both vaccines simultaneously. Conclusion: These results may support a revision of current vaccination recommendations concerning the administration of these two live attenuated vaccines either on the same day or at least 28 days apart. Our findings show no statistically significant difference if the interval between both vaccines is more than 24 h, but the immune response seems to be reduced when the two vaccines are given at the same time. (C) 2017 Elsevier Ltd. All rights reserved.

La plupart des angioedèmes sont histaminiques et correspondent à une urticaire profonde.

The recommendations on travelers' immunizations are regularly evolving in accordance with the data of clinical studies and the epidemiological situation in the world. The recent changes concern the schedule of injections: primovaccination DTCaPolio of children and boosters for adults, accelerated schedule of Japanese encephalitis and hepatitis B immunization, preexposure rabies immunization and vaccination against yellow fever; and the indications of poliomyelitis vaccine, immunization of children against Japanese encephalitis and conjugated vaccines against meningococcal meningitis.

Most angioedemas are histaminergic and correspond to deep urticarial swelling. Recurrent histaminergic angioedema led to the diagnosis of chronic urticaria, even when there are no superficial associated hives.Chronic urticaria is a benign disease, and autoimmune in 40 % of cases.The occurrence of angioedemo in chronic urticaria is not a sign of severity.The occurrence of angioedema in chronic urticoria is associated with a longer duration of urticarial disease.NSAIDs and/or systemic corticotherapy are classic triggers of angioedema in chronic urticorio. In the absence of clinical endpoints, there is no need to make further assessment in chronic urticaria good responders to antihistamines.

BACKGROUND:Multidrug-resistant Enterobacteriaceae (MRE) are widespread in the community, especially in tropical regions. Travelers are at risk of acquiring MRE in these regions, but the precise extent of the problem is not known.METHODS:From February 2012 to April 2013, travelers attending 6 international vaccination centers in the Paris area prior to traveling to tropical regions were asked to provide a fecal sample before and after their trip. Those found to have acquired MRE were asked to send fecal samples 1, 2, 3, 6, and 12 months after their return, or until MRE was no longer detected. The fecal relative abundance of MRE among all Enterobacteriaceae was determined in each carrier.RESULTS:Among 824 participating travelers, 574 provided fecal samples before and after travel and were not MRE carriers before departure. Of these, 292 (50.9%) acquired an average of 1.8 MRE. Three travelers (0.5%) acquired carbapenemase-producing Enterobacteriaceae. The acquisition rate was higher in Asia (142/196 [72.4%]) than in sub-Saharan Africa (93/195 [47.7%]) or Latin America (57/183 [31.1%]). MRE acquisition was associated with the type of travel, diarrhea, and exposure to β-lactams during the travel. Three months after return, 4.7% of the travelers carried MRE. Carriage lasted longer in travelers returning from Asia and in travelers with a high relative abundance of MRE at return.CONCLUSIONS:MRE acquisition is very frequent among travelers to tropical regions. Travel to these regions should be considered a risk factor of MRE carriage during the first 3 months after return, but not beyond.CLINICAL TRIALS REGISTRATION:NCT01526187.