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The physiopathological mechanisms responsible for digestive symptoms in COVID-19 patients are still unclear. The aim of this study was to determine the influence of faecal viral shedding on digestive symptoms and propose differential diagnoses in order to understand the gastrointestinal clinical spectrum in acute cases of COVID-19. All patients managed between March and May 2020, from whom stool samples were collected for microbiological investigations, were included. Microbiological analysis consisted of syndromic PCR screening and microscopic parasitological examination supplemented with microsporidia and multiplex protozoa PCR. SARS-CoV-2 infection was diagnosed via viral detection in respiratory and frozen stool samples, completed via serological test when necessary. Epidemiological, clinical, radiological, and biological data and clinical courses were compared according to COVID-19 status and faecal SARS-CoV-2 shedding and enteric co-infection status. The sample included 50 COVID+ and 67 COVID− patients. Faecal viral shedding was detected in 50% of stool samples and was associated with a higher viral load in the upper respiratory tract. Detected enteric pathogens were not different between subjects with different COVID-19 statuses or faecal SARS-CoV-2 shedding and had no impact on the clinical course for COVID-19 patients. The connection between SARS-CoV-2 shedding and enteric pathogen co-infection involvement in gastrointestinal presentation and clinical course is still unclear, suggesting other processes are involved in digestive disorders in COVID-19 patients.

Corynebacterium spp. are associated with respiratory infections in immunocompromised hosts. A link with bronchial complications after lung transplantation (LTx) has been suggested. We aimed to assess the link between respiratory sampling of Corynebacterium spp. and significant bronchial complication (SBC) after LTx. We performed a single center retrospective study. Inclusion of LTx recipients with at least one respiratory Corynebacterium spp. sample (July 2014 to December 2018). Subjects were matched to unexposed LTx recipients. Primary outcome was SBC occurrence after Corynebacterium spp. isolation. Secondary outcomes were Corynebacterium spp. persistent sampling, chronic lung allograft dysfunction (CLAD) onset and all-cause mortality. Fifty-nine patients with Corynebacterium spp. sampling with 59 without isolation were included. Corynebacterium spp. identification was not associated with SBC occurrence (32.4% vs. 21.6%, p = 0.342). Previous SBC was associated with further isolation of Corynebacterium spp. (OR 3.94, 95% CI [1.72–9.05]). Previous SBC and corticosteroids pulses in the last 3 months were the only factors associated with increased risk of Corynebacterium spp. isolation in multivariate analysis. Corynebacterium spp. sampling was significantly associated with CLAD onset (27.1% vs. 6.9%, p = 0.021). Corynebacterium spp. isolation was not associated with SBC but with higher risk of CLAD. Whether CLAD evolution is affected by Corynebacterium spp. eradication remains to be investigated.

SummaryBackgroundAntimicrobial resistance is a major public health threat, affecting not only humans but also animals and the environment. Although the “One Health” dimension of resistance is well recognized, data are lacking on the circulation of resistance, particularly in low-income countries. The World Health Organization has proposed a protocol called Tricycle, focusing on extended-spectrum beta-lactamase (ESBL)-Escherichia colisurveillance in the three sectors. We implemented Tricycle in Madagascar to assess ESBL-E. coliprevalence and describe intra- and inter-sector circulation of ESBL-E. coliand plasmids.Methods289 pregnant women, 246 farm chickens and 28 surface waters were sampled in Antananarivo (the capital city) area and tested for ESBL-E. coli. Isolates were sequenced by short-(Illumina) and long-(Nanopore) read methods.FindingsESBL-E. coliprevalence was 29·8%, 56·9% and 100% in pregnant women, chickens, and the environment, respectively. The wet season was associated with higher rates of carriage in humans (OR=3·1, 95%CI 1·8-5·3) and animals (OR=2·8 95%CI 1·7-4·8). Sequencing of 277 non-duplicated isolates (82, 118 and 77 from each sector, respectively) showed high genetic diversity (90 STs identified) with differences between sectors. Single nucleotide polymorphism (SNP) analysis revealed 169/277 (61%) isolates grouped into 44 clusters (≥2 isolates) of closely related isolates (blaCTX-M(77.6%blaCTX-M-15), chromosomally integrated in 57·4% (159/277) of isolates, and plasmidic in 40·8% (113/277). The 114 ESBL-carrying plasmids were mainly IncF (55·2%, n=63) and IncY (36·8%, n=42). The F31/36:A4:B1 (n=13) and F-:A-:B53 (n=8) subtypes, and all IncY plasmids, highly conserved, were observed in isolates of differing genetic backgrounds from all sectors.InterpretationDespite varying strain population structures in the three sectors, both ESBL-E. colistrains and plasmids are circulating among humans, chickens and the environment in the capital of Madagascar.FundingFondation Mérieux, INSERM, Université Paris Cité

Background Pneumonia is a common illness, accounting for a staggering amount of worldwide morbidity and mortality. The diagnosis of pneumonia is challenging given the variety of responsible pathogens. Diagnostic testing for bacterial pneumonia has traditionally relied on time-consuming culture-based methods, though recently multiplexed molecular approaches have been described. Multiplexed molecular assays for pneumonia have the potential to provide broad diagnostic information in a rapid timeframe. Much has yet to be learned about these assays regarding analytical performance, potential impact, and optimal implementation strategy. Content Herein we provide a summary of what is known and what has yet to be learned about multiplexed molecular pneumonia assays. We provide a comparison of the different commercially available assays and summarize the most current performance data for each. We further describe outcome data and lessons learned from those who have implemented these assays worldwide. Finally, based on the current state of performance and outcome data, we provide informed strategies and considerations for laboratories contemplating implementation. Summary Multiplexed molecular assays for the diagnosis of pneumonia boast high accuracy though the diagnostic information gained from these assays is inherently different from culture and must be interpreted in cultural context. Despite this, these assays can be powerful and effective diagnostic tools with a potential to positively impact patient care. The extent to which this is realized varies from setting to setting, though is dependent on thoughtful implementation and a focus on delivering clear, rapid, and actionable results that can be interpreted in the appropriate context.

Colistin is an antibiotic of last resort in the management of highly drug-resistant Enterobacterales infections. Travel to some destinations presents a high risk of acquiring multidrug-resistant Enterobacterales, but little data are available on the risk of acquiring colistin-resistant strains. Here, we use the VOYAG-R sample collection (2012-2013) in order to evaluate the rate of acquisition of colistin-resistant Enterobacterales, excluding species with intrinsic resistance (CRE), following travel to tropical regions.A total of 574 frozen stool samples of travellers returning from tropical regions was screened for colistin-resistant strains using ChromID Colistin R agar (bioMerieux®) after pre-enrichment culture with 1 mg/L of colistin. Genomes were obtained by Illumina sequencing and genetic determinants of colistin resistance (mutational events and mcr genes) were searched.A total of 22 travellers (3.8%) acquired colistin-resistant Enterobacterales carrying an mcr gene. Acquisition rates varied between visited regions: 9.2% (18/195) for Asia (Southeast Asia: 17/18), 2.2% (4/184) for Latin America (Peru: 4/4) and 0% from Africa (0/195). Acquired strains were predominantly Escherichia coli (92%) and carried mostly the mcr-1 variant (83%). E. coli strains belonged mainly to commensal phylogroups A and B1, and were genetically highly diverse (5 non-clonal Sequence Type (ST)10 and 17 ST singletons). Only four non mcr colistin-resistant strains (two E. coli and two Enterobacter cloacae complex) were identified. Among all the strains, two also carried extended-spectrum beta-lactamase (ESBL) genes.Travel to tropical regions, and particularly to Southeast Asia, is a risk factor for the acquisition of mcr-carrying Enterobacterales. This study highlights the community dissemination of mcr in humans as early as 2012, 4 years prior to its first published description.

The Proteus mirabilis PmirS clinical isolate, which was susceptible to imipenem (0.5 μg/mL) and amikacin (1 μg/mL), was recovered from a bronchial aspirate of a patient who recently underwent lung ...

Objectives: Physiopathological mechanisms responsible for digestive symptoms during COVID-19 are still unclear. The aim of this study was to determine the influence of faecal viral shedding on digestive symptoms and propose differential diagnoses to better understand the gastrointestinal clinical spectrum during acute COVID-19.Methods: Patients were included if one stool sample was available for microbiological investigation. Microbiological analysis consisted of syndromic PCR screening, and parasitological investigation included microsporidia and multiplex protozoa PCR. SARS-CoV-2 infection was diagnosed by viral detection (on respiratory samples and frozen stool samples) and by serology when necessary. Collected epidemiological, clinical, radiological, biological data and clinical course were compared according to COVID-19 status, faecal SARS-CoV-2 shedding and co-infection status.Results: 50 COVID+ and 67 COVID- patients were included. Faecal viral shedding was detected in 50% of stool samples and was associated with higher viral load in the upper respiratory tract. There was no difference in the proportion of detected enteric pathogens between COVID-19 status. No impact was observed on clinical course regardless of COVID-19 status, faecal SARS-CoV-2 shedding and coinfection status.Conclusions: SARS-CoV-2 shedding and enteric pathogen involvement in gastrointestinal presentation is still unclear. However, differential diagnostic investigation revealed frequently occurring common enteric pathogens in COVID-19 patients.

Because the diagnosis of co/superinfection in COVID-19 patients is challenging, empirical antibiotic therapy is frequently initiated until microbiological analysis results. We evaluated the performance and the impact of the BioFire® FilmArray® Pneumonia plus Panel on 112 respiratory samples from 67 COVID-19 ICU patients suspected of co/superinfections. Globally, the sensitivity and specificity of the test were 89.3% and 99.1%, respectively. Positive tests led to antibiotic initiation or adaptation in 15% of episodes and de-escalation in 4%. When negative, 28% of episodes remained antibiotic-free (14% no initiation, 14% withdrawal). Rapid multiplex PCRs can help to improve antibiotic stewardship by administering appropriate antibiotics earlier and avoiding unnecessary prescriptions. Supplementary Information The online version contains supplementary material available at 10.1007/s10096-021-04213-6.

Purpose of review Pneumonia represents a major burden in clinical practice. A rapid etiological diagnosis is critical for optimizing the antibiotic use. Owing to the variety of possible pathogens and the time needed for bacterial cultures or usual polymerase chain reaction (PCR) assays, timely and precise diagnosis is a huge challenge. Several new rapid multiplex assays have been developed in the last decade to resolve these issues. This review aims to provide an overview of recent evidence on improvements and limitations of new rapid molecular assays for pneumonia. Recent findings Several rapid multiplex-PCR assays are commercially available for upper or lower respiratory tract samples, allowing detection of a wide range of respiratory viruses, bacteria, and, in some cases, of several antibiotic resistance genes. Clinical evaluations demonstrated their good correlation with gold-standard assays but their lack of exhaustiveness, especially for hospital-acquired pneumonia. Studies that evaluated their potential benefits on antibiotic use suffered from important weaknesses with conflicting and limited results. Summary New molecular assays may enable improvements in patient management and antibiotic use. Available studies highlight several benefits and the strong interrelations needed between microbiologists and physicians for their implementation and interpretation according to the clinical and epidemiological context.

Summary Background Colonization pressure is a risk factor for intensive care unit (ICU)-acquired multi-drug-resistant organisms (MDROs). Aim To measure the long-term respective impact of colonization pressure on ICU-acquired extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA). Methods All patients admitted to two ICUs (medical and surgical) between January 1997 and December 2015 were included in this retrospective observational study. Rectal and nasal surveillance cultures were obtained at admission and weekly thereafter. Contact precautions were applied for colonized or infected patients. Colonization pressure was defined as the ratio of the number of MDRO-positive patient-days (PDs) of each MDRO to the total number of PDs. Single-level negative binomial regression models were used to evaluate the incidence of weekly MDRO acquisition. Findings Among the 23,423 patients included, 2327 (10.0%) and 1422 (6.1%) were colonized with ESBL-PE and MRSA, respectively, including 660 (2.8%) and 351 (1.5%) acquisitions. ESBL-PE acquisition increased from 0.51/1000 patient-exposed days (PEDs) in 1997 to 6.06/1000 PEDs in 2015 (P Conclusion Colonization pressure contributed to the increasing incidence of ESBL-PE but not MRSA. This study suggests that preventive control measures should be customized to MDROs.

International audience; OBJECTIVES: To evaluate performances of the rapid multiplex PCR assay BioFire FilmArray Pneumonia Panel (FA-PP) for detection of bacterial pathogens and antibiotic resistance genes in sputum, endotracheal aspirate (ETA) and bronchoalveolar lavage (BAL) specimens. METHODS: This prospective observational study was conducted in 11 French university hospitals (July to December 2018) and assessed performance of FA-PP by comparison with routine conventional methods. RESULTS: A total of 515 respiratory specimens were studied, including 58 sputa, 217 ETA and 240 BAL. The FA-PP detected at least one pathogen in 384 specimens, yielding an overall positivity rate of 74.6% (384/515). Of them, 353 (68.5%) specimens were positive for typical bacteria while eight atypical bacteria and 42 resistance genes were found. While identifying most bacterial pathogens isolated by culture (374/396, 94.4%), the FA-PP detected 294 additional species in 37.7% (194/515) of specimens. The FA-PP demonstrated positive percentage agreement and negative percentage agreement values of 94.4% (95% CI 91.7%-96.5%) and 96.0% (95% CI 95.5%-96.4%), respectively, when compared with culture. Of FA-PP false-negative results, 67.6% (46/68) corresponded to bacterial species not included in the panel. At the same semi-quantification level (in DNA copies/mL for FA-PP versus in CFU/mL for culture), the concordance rate was 43.4% (142/327) for culture-positive specimens with FA-PP reporting higher semi-quantification of ≥1 log(10) in 48.6% (159/327) of cases. Interestingly, 90.1% of detected bacteria with ≥10(6) DNA copies/mL grew significantly in culture. CONCLUSIONS: FA-PP is a simple and rapid molecular test that could complement routine conventional methods for improvement of diagnosis accuracy of pneumonia.

Objectives: Intestinal carriage with extended spectrum β-lactamase Enterobacteriaceae (ESBL-E) and carbapenemase-producing Enterobacteriaceae (CPE) can persist for months. We aimed to evaluate whether oral antibiotics followed by faecal microbiota transplantation (FMT) can eradicate intestinal carriage with ESBL-E/CPE.Methods: Randomized, open-label, superiority trial in four tertiary-care centres (Geneva (G), Paris (P), Utrecht (U), Tel Aviv (T)). Non-immunocompromised adult patients were randomized 1: 1 to either no intervention (control) or a 5-day course of oral antibiotics (colistin sulphate 2 × 106 IU 4×/day; neomycin sulphate 500 mg 4×/day) followed by frozen FMT obtained from unrelated healthy donors. The primary outcome was detectable intestinal carriage of ESBL-E/CPE by stool culture 35-48 days after randomization (V4). ClinicalTrials.govNCT02472600. The trial was funded by the European Commission (FP7).Results: Thirty-nine patients (G = 14; P = 16; U = 7; T = 2) colonized by ESBL-E (n = 36) and/or CPE (n = 11) were enrolled between February 2016 and June 2017. In the intention-to-treat analysis 9/22 (41%) patients assigned to the intervention arm were negative for ESBL-E/CPE at V4 (1/22 not receiving the intervention imputed as positive) whereas in the control arm 5/17 (29%) patients were negative (one lost to follow up imputed as negative) resulting in an OR for decolonization success of 1.7 (95% CI 0.4-6.4). Study drugs were well tolerated overall but three patients in the intervention group prematurely stopped the study antibiotics because of diarrhoea (all received FMT).Conclusions: Non-absorbable antibiotics followed by FMT slightly decreased ESBL-E/CPE carriage compared with controls; this difference was not statistically significant, potentially due to early trial termination. Further clinical investigations seem warranted.

International audience; In a prospective, nationwide study in France of Escherichia coli responsible for pneumonia in patients receiving mechanical ventilation, we determined E. coli antimicrobial susceptibility, phylotype, O-type, and virulence factor gene content. We compared 260 isolates with those of 2 published collections containing commensal and bacteremia isolates. The preponderant phylogenetic group was B2 (59.6%), and the predominant sequence type complex (STc) was STc73. STc127 and STc141 were overrepresented and STc95 underrepresented in pneumonia isolates compared with bacteremia isolates. Pneumonia isolates carried higher proportions of virulence genes sfa/foc, papGIII, hlyC, cnf1, and iroN compared with bacteremia isolates. Virulence factor gene content and antimicrobial drug resistance were higher in pneumonia than in commensal isolates. Genomic and phylogenetic characteristics of E. coli pneumonia isolates from critically ill patients indicate that they belong to the extraintestinal pathogenic E. coli pathovar but have distinguishable lung-specific traits.

Objectives Our aim was to evaluate the prevalence and associated factors for carriage of extended-spectrum β-lactamase-producing enterobacteria (ESBL-PE) in a healthcare facility. Methods In 2016 a serial cross-sectional survey of ESBL-PE carriage in a French university hospital was conducted. All patients present on the day of the survey were screened for ESBL-PE carriage. Demographic characteristics and risk factors for ESBL-PE carriage were collected. Results In all, 146/844 patients (17%) were digestive carriers of ESBL-PE; of these, 96 (66%) had not previously been identified. Among patients carrying ESBL-PE, Escherichia coli (62%) and CTX-M type (94%) predominated. Greater age, recent travel abroad, receipt of antibiotic, and prolonged hospitalization were associated with ESBL-PE carriage. Conclusion Given the high prevalence of ESBL-PE and the high proportion of unknown carriers, our results strongly suggest reinforcing standard precautions rather than contact precautions for controlling the spread of ESBL-PE.

Sternal wound infection (SWI) after cardiac surgery is a severe complication. Among preventive measures, pre-operative decolonization of nasal carriage of Staphylococcus aureus has recently been shown to be beneficial. This quasi-experimental study assessed the effect of decolonization on the incidence of S. aureus-associated SWI based on 19 years of prospective surveillance.Segmented negative binomial regression was used to analyse the change over time in the incidence of S. aureus mediastinitis requiring re-operation after cardiac surgery in a French university hospital between 1996 and 2014. Universal nasal decolonization with mupirocin was introduced in December 2001. The association between pre-operative nasal carriage and SWI due to S. aureus was analysed between 2006 and 2012.Among 17,261 patients who underwent a cardiac surgical procedure, 565 developed SWI (3.3%), which was caused by S. aureus in 181 cases (1%). The incidence of mediastinitis caused by S. aureus decreased significantly over the study period (1.43% in 1996-2001 vs 0.61% and 0.64% in 2002-2005 and 2006-2014, respectively; P0.001). In segmented analysis, there was a significant break in 2002, corresponding to the introduction of decolonization. Despite this intervention, pre-operative nasal carriage remained a significant risk factor for S. aureus mediastinitis (adjusted odds ratio 2.2; 95% confidence interval 1.2-4.2), as were obesity, critical pre-operative status, coronary artery bypass grafting (CABG), and combined surgery with valve replacement and CABG.Universal nasal decolonization before cardiac surgery was effective in decreasing the incidence of mediastinitis caused by S. aureus. Nasal carriage of S. aureus remained a risk factor for S. aureus-associated SWI.

Among 197 COVID-19 patients hospitalized in ICU, 88 (44.7%) experienced at least one bacterial infection, with pneumonia (39.1%) and bloodstream infections (15,7%) being the most frequent. Unusual findings include frequent suspicion of bacterial translocations originating from the digestive tract as well as bacterial persistence in the lungs despite adequate therapy.

International audience; INTRODUCTION: At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. METHODS AND ANALYSIS: The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician's discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. ETHICS AND DISSEMINATION: The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. TRIAL REGISTRATION NUMBER: NCT03452826; Pre-results.

The

Travel abroad is associated with a high risk of acquiring multidrug-resistant Enterobacterales (MDR-E) [i.e., extended-spectrum beta-lactamase–producing Enterobacterales (ESBL-E) and plasmid-mediated-AmpC beta-lactamase–producing Enterobacterales (pAmpC-E)]. Here, we evaluated the utility of pre-enrichment and performance of screening for MDR-E using 2 different media (ChromID-ESBL and biplate-ESBL) from 574 traveler stool samples. ESBL-E and MDR-E were detected in 49% (281/574) and 51% (296/574) of travelers, respectively. Pre-enrichment improved the detection of ESBL-E and MDR-E by 11.7% and 12.5%, respectively, without decreasing specificity (88.4% versus 87.4% for ESBL-E screening and 92.4% versus 89.9% for MDR-E screening). Sensitivity of the biplate-ESBL agar was higher than for ChromID-ESBL for ESBL-E detection (92.9% versus 86.1%), but specificity was lower (64.2% versus 87.4%). Whereas pAmpC-E were all detected by biplate-ESBL, 96% (47/49) and 82% (40/49) were detected by ChromID-ESBL, respectively, with and without pre-enrichment. Pre-enrichment increases the performance of MDR-E screening, especially in individuals with low MDR-E digestive abundance.

SETTING: Tuberculosis (TB) incidence is declining overall in France, but not in Paris where some areas remain relative hot spots for TB.OBJECTIVES: To obtain a better knowledge of local TB epidemiology in order to facilitate control measures.DESIGN: Analysis of demographic data of TB patients diagnosed at the Bichat-Claude Bernard Hospital from 2007 to 2016, with spoligotyping of Mycobacterium tuberculosis complex isolates.RESULTS: During the study period, 1096 TB patients were analysed. The incidence of TB diagnosis was stable, averaging 115 patients per year, predominantly males (71%), foreign-born (81%), with pulmonary TB (77%) and negative HIV serology (88%). The mean age of foreign-born TB patients decreased over the study period, most significantly in recent arrivals in France, whose average age decreased by two years (P = 0.001). The time period between arrival in France and being diagnosed with active TB decreased annually significantly by 0.75 years (P = 0.02). The proportion of L4.6.2/Cameroon and L2/Beijing sub-lineages increased annually by 0.7% (P < 0.05). Multi-drug resistant strains, representing 4% of all strains, increased annually by 0.75% (P = 0.03)CONCLUSION: The number of TB patients remained high in northern Paris and the surrounding suburbs, suggesting the need for increased control measures.

ObjectivesRoutine amoxicillin for children with uncomplicated severe acute malnutrition raises concerns of increasing antibiotic resistance. We performed an ancillary study nested within a double-blind, placebo-controlled trial in Niger testing the role of routine 7 day amoxicillin therapy in nutritional recovery of children 6 to 59 months of age with uncomplicated severe acute malnutrition.MethodsWe screened 472 children for rectal carriage of ESBL-producing Enterobacteriaceae (ESBL-E) as well as their household siblings under 5 years old, at baseline and Week 1 (W1) and Week 4 (W4) after start of therapy, and characterized strains by WGS. ClinicalTrials.gov: NCT01613547.ResultsCarriage in index children at baseline was similar in the amoxicillin and the placebo groups (33.8% versus 27.9%, P = 0.17). However, acquisition of ESBL-E in index children at W1 was higher in the amoxicillin group than in the placebo group (53.7% versus 32.2%, adjusted risk ratio = 2.29, P = 0.001). Among 209 index and sibling households possibly exposed to ESBL-E transmission, 16 (7.7%) had paired strains differing by ≤10 SNPs, suggesting a high probability of transmission. This was more frequent in households from the amoxicillin group than from the placebo group [11.5% (12/104) versus 3.8% (4/105), P = 0.04].ConclusionsAmong children exposed to amoxicillin, ESBL-E colonization was more frequent and the risk of transmission to siblings higher. Routine amoxicillin should be carefully balanced with the risks associated with ESBL-E colonization.

Resume Le nombre de touristes internationaux ne cesse d’augmenter chaque annee tout comme les infections observees au retour de voyage, parmi celles-ci, on retrouve les infections sexuellement transmissibles (IST). Lors de voyages, il est connu que la prise de risque lors de rapports sexuels est augmentee. Si un certain nombre de micro-organismes responsables d’IST comme les Chlamydiae trachomatis, Neisseria gonorrhoeae ou Trichomonas vaginalis, sont cosmopolites, certains comme Haemophilus ducreyi restent endemiques dans plusieurs regions. Les souches de N. gonorrhoeae circulant en zones intertropicales presentent aussi des taux de resistance aux antibiotiques tres eleves. Dans ce contexte, la place du biologiste medical est majeure, en pre analytique pour le recueil de donnees cliniques et epidemiologiques afin d’adapter les examens a realiser comme en postanalytique pour aider le clinicien dans le choix des traitements, donner des conseils aux patients et participer a la surveillance epidemiologique des infections.

Resume Le nombre de voyages a l'etranger ne cesse d'augmenter depuis ces dix dernieres annees ainsi que le nombre d'infections observees au retour de ces voyages. Parmi celles-ci, on retrouve les infections urinaires. Le diagnostic des infections urinaires ne possede pas de specificite liee aux voyages meme si dans ce contexte, leur frequence semble plus elevee. Les voyages a l'etranger, plus particulierement en zone intertropicale, constituent un facteur de risque de faire une infection a bacterie multiresistante. En effet, les taux d'acquisition de portage digestif d'enterobacteries multiresistantes sont eleves apres un voyage notamment en zones intertropicales et sont associes a un risque plus eleve de faire une infection urinaire a bacterie multiresistante. Dans ce contexte, la place du biologiste medicale est cruciale, en pre analytique dans le cadre du recueil de donnees cliniques et epidemiologiques precises pour adapter l'etude de la sensibilite aux anti-infectieux comme en postanalytique afin d'aider le clinicien dans le choix des traitements, conseiller les patients et participer activement a la surveillance epidemiologique de ces infections.

Background Enterobacteriaceae have become increasingly resistant, especially due to the acquisition and spread of extended-spectrum beta-lactamases (ESBLs), which confer resistance to the majority of beta-lactams. Multi-resistant Enterobacteriaceae (MRE) were first isolated in hospitals, but now they are disseminating in the community setting, mostly in low and middle income countries. Consequently, the increasing number of international travels leads to the importation of MRE from high-prevalence to low-prevalence countries. Methods The Pubmed database was used to conduct research from 1980 to 2016 by combining the following key words: travel, antibiotic resistance, ESBL, Enterobacteriaceae, genomic, metagenomic, urinary tract infection, infection. Results The research found that the MRE acquisition rates in healthy travellers from low-prevalence countries ranged from 21% to 51% depending on the study design and the visited geographic regions. After a trip to Asia and especially to South Asia, the acquisition rate could reach 85%. A trip to Africa or to the Middle East was associated with lower rates but still worrisome (13–44%). Digestive disorder, diarrhoea and antibiotics used during travel are major risks factors associated with the acquisition of MRE. Travel to endemic areas has also been identified as a risk factor for MRE infection, including urinary tract infections. Conclusion Travellers are at high risk of MRE acquisition and consequently of MRE infection. This risk should not be ignored by general practitioners. To reduce the risk of acquisition and subsequent transmission to relatives, travellers should be given recommendations prior to their travel.

Introduction At the time of the worrying emergence and spread of bacterial resistance, reducing the selection pressure by reducing the exposure to antibiotics in patients with community-acquired pneumonia (CAP) is a public health issue. In this context, the combined use of molecular tests and biomarkers for guiding antibiotics discontinuation is attractive. Therefore, we have designed a trial comparing an integrated approach of diagnosis and treatment of severe CAP to usual care. Methods and analysis The multiplex PCR and procalcitonin to reduce duration of antibiotics exposure in patients with severe-CAP (MULTI-CAP) trial is a multicentre (n=20), parallel-group, superiority, open-label, randomised trial. Patients are included if adult admitted to intensive care unit for a CAP. Diagnosis of pneumonia is based on clinical criteria and a newly appeared parenchymal infiltrate. Immunocompromised patients are excluded. Subjects are randomised (1:1 ratio) to either the intervention arm (experimental strategy) or the control arm (usual strategy). In the intervention arm, the microbiological diagnosis combines a respiratory multiplex PCR (mPCR) and conventional microbiological investigations. An algorithm of early antibiotic de-escalation or discontinuation is recommended, based on mPCR results and the procalcitonin value. In the control arm, only conventional microbiological investigations are performed and antibiotics de-escalation remains at the clinician’s discretion. The primary endpoint is the number of days alive without any antibiotic from the randomisation to day 28. Based on our hypothesis of 2 days gain in the intervention arm, we aim to enrol a total of 450 patients over a 30-month period. Ethics and dissemination The MULTI-CAP trial is conducted according to the principles of the Declaration of Helsinki, is registered in Clinical Trials and has been approved by the Committee for Protection of Persons and the National French Drug Safety Agency. Written informed consents are obtained from all the patients (or representatives). The results will be disseminated through educational institutions, submitted to peer-reviewed journals for publication and presented at medical congresses. Trial registration number NCT03452826; Pre-results.

The aim of our study was to determine the frequency of extended-spectrum beta-lactamase (ESBL) phenotypes among the enterobacteria present in blood cultures of patients at admission to two university hospitals of Bamako (Mali). During a period of three months, we isolated enterobacteria from blood cultures from patients upon admission to the Point G and Gabriel Toure University Hospitals. The ESBL-positive enterobacteria were initially identified by API 20E strips and VITEK®2 and then confirmed in France by MALDI-TOF mass spectrometry at the Bichat Hospital bacteriology laboratory. Antibiotic susceptibility was determined by the diffusion method as recommended by EUCAST. The species isolated were K. pneumoniae (14/40, 35.0 %), E. coli (11/40, 27.5 %), and E. cloacae (9/40, 22.5 %); 21/34 (61.8 %) had an ESBL phenotype, including 10/14 (71.4 %) K. pneumoniae, 8/11 (72.7 %) E. coli, and 3/9 (33 3 %), E. cloacae. The ESBL strains of K. pneumoniae, E. coli, and E. cloacae were associated, respectively, with resistance to the following antibiotics: gentamicin (10/10, 100 %; 6/8, 75%; 2/3, 67%), amikacin (2/10, 20 %; 0/8, 0%; 0/3, 0%), ofloxacin (8/10, 80. %; 7/8, 87%; 3/3, 100%), cotrimoxazole (10/10, 100 %; 6/8, 75%; 3/3, 100%). Almost two thirds (61.8%) of the enterobacteria isolated from blood cultures produced extended-spectrum beta-lactamases. They retained regular sensitivity only to carbapenems and amikacin.

Resume Longtemps restees cantonnees au milieu hospitalier, les enterobacteries productrices de beta-lactamases a spectre etendu (E-BLSE) diffusent desormais largement dans la communaute. Les taux de portage d’E-BLSE dans la population sont extremement variables selon les zones geographiques (5 % en Europe a 50 % en Asie). En France, cette prevalence est estimee autour de 5 a 6 % et les facteurs de risque frequemment associes au portage sont une prise recente d’antibiotique et un voyage recent a l’etranger. La proportion d’E-BLSE au sein des infections urinaires est egalement liee a la zone geographique et aux taux de portage dans la communaute. En France, meme si cette proportion reste faible (2 a 5 %), c’est un risque qui ne doit pas etre neglige surtout chez les sujets revenant d’un sejour en zone d’endemie.

Purpose In ICU patients with carriage of extended spectrum beta-lactamase producing Enterobacterales (ESBL-E) and suspected Gram-negative bacilli ventilator-associated pneumonia (GNB-VAP), the quantification of the rectal and throat ESBL-E carriage might predict the ESBL-E involvement in GNB-VAP. Our aim was to evaluate whether a semi-quantitative assessment of rectal/throat ESBL-E carriage can predict ESBL-E-associated VAP in medical ICU patients. Methods From May 2014 to May 2017, all ESBL-E carriers had a semi-quantitative assessment of ESBL-E density in swabs cultures. For those who developed GNB-VAP (diagnosed using bronchoalveolar lavage or plugged telescopic catheter with significant quantitative culture), the last positive swab collected at least 48 h before GNB-VAP onset was selected. Clinical data were extracted from a prospectively collected database. Results Among 365 ESBL-E carriers, 82 developed 107 episodes of GNB-VAP (ESBL-E VAP, n = 50; and non-ESBL-E GNB-VAP, n = 57) after 13 days of mechanical ventilation in median. Antimicrobials use before VAP onset was similar between groups. The last swabs were collected 5 days in median before VAP onset. ESBL-E. coli carriers developed ESBL-E VAP less frequently (n = 13, 34%) than others (n = 32, 67.3%, p

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.

Introduction: The increasing frequency of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae is becoming a serious public health concern. This study sought to determine ESBL frequency in Enterobacteriaceae isolated from patients’ blood cultures in two university teaching hospitals of Bamako, Mali. Methodology: During a three-month period, the presence of Enterobacteriaceae from blood cultures of patients admitted to the university teaching hospitals of Bamako was evaluated. The microbial identifications were initially performed with an API 20E gallery and VITEK2 locally in Mali, and then confirmation in France was performed with a mass spectrometry MALDI-TOF in the bacteriology laboratory of the university teaching hospital of Bichat. Antibiotic susceptibility profiles were determined by the diffusion method as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: The isolated species were K. pneumoniae (14/40; 35.0%), E. coli (11/40; 27.5%), and E. cloacae (9/40; 22.5%). Of the strains isolated, 21/34 (61.8%) had an ESBL phenotype, including 10/14 (71.4%) K. pneumoniae , 8/11 (72.7%) E. coli , and 3/9 (33.3%) E. cloacae . Resistances associated with ESBL strains of K. pneumoniae , E. coli , and E. cloacae were as follows: gentamicin (10/10, 100%; 6/8, 75%; 2/3, 67%, respectively), amikacin (2/10, 20%; 0/8, 0%; 0/3, 0%, respectively), ofloxacin (8/10, 80%; 7/8, 87%; 3/3, 100%, respectively), and cotrimoxazole (10/10, 100%; 6/8, 75%; 3/3, 100%, respectively). Conclusion: Almost two-thirds (61.8%) of Enterobacteriaceae isolated from our blood cultures were ESBL producers. Only susceptibilities to carbapenems and to amikacin were fully conserved within the strains.

International audience; OBJECTIVES:Acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) by Europeans travelling individually in high-endemicity countries is common. However, how the different ESBL-E strains circulate in groups of travellers has not been studied. We investigated ESBL-E transmission within several groups of French military personnel serving overseas for 4-6 months.METHODS:We conducted a prospective study among French military personnel assigned to Afghanistan, French Guiana or Côte d'Ivoire for 4-6 months. Faecal samples provided by volunteers before leaving and after returning were screened for ESBL-E isolates. ESBL Escherichia coli from each military group was characterized by repetitive element palindromic polymerase chain reaction (rep-PCR) fingerprinting followed, in the Afghanistan group, by whole-genome sequencing (WGS) if similarity was ≥97%.RESULTS:Among the 189 volunteers whose samples were negative before departure, 72 (38%) were positive after return. The highest acquisition rates were observed in the Afghanistan (29/33, 88%) and Côte d'Ivoire (39/80, 49%) groups. Acquisition rates on return from French Guiana were much lower (4/76, 5%). WGS of the 20 strains from the Afghanistan group that clustered by rep-PCR identified differences in sequence type, serotype, resistance genes and plasmid replicons. Moreover, single-nucleotide polymorphism (SNP) differences across acquired strains from a given cluster ranged from 30 to 3641, suggesting absence of direct transmission.CONCLUSIONS:ESBL-E. coli acquisition was common among military personnel posted overseas. Many strains clustered by rep-PCR but differed by WGS and SNP analysis, suggesting acquisition from common external sources rather than direct person-to-person transmission.

In a phase 1 clinical study, coadministration of the adsorbent-based DAV132 product together with the fluoroquinolone antibiotic moxifloxacin, while not affecting the plasma concentrations of the antibiotic, reduced by >99% exposure of the intestinal microbiota to the moxifloxacin., Background Antibiotics are life-saving drugs but severely affect the gut microbiome with short-term consequences including diarrhea and selection of antibiotic-resistant bacteria. Long-term links to allergy and obesity are also suggested. We devised a product, DAV132, and previously showed its ability to deliver a powerful adsorbent, activated charcoal, in the late ileum of human volunteers. Methods We performed a randomized controlled trial in 28 human volunteers treated with a 5-day clinical regimen of the fluoroquinolone antibiotic moxifloxacin in 2 parallel groups, with or without DAV132 coadministration. Two control goups of 8 volunteers each receiving DAV132 alone, or a nonactive substitute, were added. Results The coadministration of DAV132 decreased free moxifloxacin fecal concentrations by 99%, while plasmatic levels were unaffected. Shotgun quantitative metagenomics showed that the richness and composition of the intestinal microbiota were largely preserved in subjects co-treated with DAV132 in addition to moxifloxacin. No adverse effect was observed. In addition, DAV132 efficiently adsorbed a wide range of clinically relevant antibiotics ex vivo. Conclusions DAV132 was highly effective to protect the gut microbiome of moxifloxacin-treated healthy volunteers and may constitute a clinical breakthrough by preventing adverse health consequences of a wide range of antibiotic treatments. Clinical Trials Registration NCT02176005.

Background Poor outcomes occur when patients with serious infections receive antibiotics to which the organisms are resistant. Methods Decision trees simulated in-hospital mortality, costs, incremental cost-effectiveness ratio per life year saved, and carbapenem resistance according to 3 empirical antibiotic strategies among adults hospitalized for community-acquired (CA) upper urinary tract infections (UTIs): ceftriaxone (CRO) plus gentamicin (GM) in the intensive care unit (ICU), imipenem (IMP), and individualized choice (IMP or CRO) based on clinical risk factors for CA- extended-spectrum β -lactamase (ESBL). Results The estimated prevalence of CA-ESBL on admission was 5% (range, 1.3%-17.6%); 3% and 97% were admitted to the ICU and medical ward (MW), respectively. In the ICU, CRO plus GM was dominated; IMP was cost-effective (incremental cost-effectiveness ratio: €4,400 per life year saved compared with individualized choice). In the MW, IMP had no impact on mortality and was less costly (−€142 per patient vs CRO, −€38 vs individualized choice). The dominance of IMP was consistent in sensitivity analyses. Compared with CRO, colonization by carbapenem-resistant pathogens increased by an odds ratio of 4.5 in the IMP strategy. Conclusion Among the ICU patients, empirical IMP therapy reduces mortality at an acceptable cost. Among MW patients, individualized choice or CRO is preferred to limit carbapenem resistance at a reasonable cost.

Objectives Despite recent advances, antibiotic therapy of ventilator-associated pneumonia (VAP) in ICU patients is still challenging. We assessed the impact of imipenem and amikacin pharmacokinetic and pharmacodynamic parameters on microbiological outcome in these patients. Patients and methods Patients with Gram-negative bacilli (GNB) VAP were prospectively included. Blood samples for pharmacokinetic analysis were collected after empirical administration of a combination of imipenem three times daily and one single dose of amikacin. MICs were estimated for each GNB obtained from respiratory samples. Microbiological success was defined as a ≥103 cfu/mL decrease in bacterial count in quantitative cultures between baseline and the third day of treatment. Results Thirty-nine patients [median (min–max) age = 60 years (28–84) and median SAPS2 at inclusion = 40 (19–73)] were included. Median MICs of imipenem and amikacin were 0.25 mg/L (0.094–16) and 2 mg/L (1–32), respectively. Median times over MIC and over 5× MIC for imipenem were 100% (8–100) and 74% (3–100), respectively. The median C1/MIC ratio for amikacin was 23 (1–76); 34 patients (87%) achieved a C1/MIC ≥10. Microbiological success occurred in 29 patients (74%). No imipenem pharmacodynamic parameter was significantly associated with the microbiological success. For amikacin, C1/MIC was significantly higher in the microbiological success group: 26 (1–76) versus 11 (3–26) (P = 0.004). Conclusions In ICU patients with VAP, classic imipenem pharmacodynamic targets are easily reached with usual dosing regimens. In this context, for amikacin, a higher C1/MIC ratio than previously described might be necessary.