Integrons, a predictive biomarker for antibiotic resistance in acute sepsis: the IRIS study.

BACKGROUND: Considering the increase in MDR Gram-negative bacteria (GNB), the choice of empirical antibiotic therapy is challenging. In parallel, use of broad-spectrum antibiotics should be avoided to decrease antibiotic selection pressure. Accordingly, clinicians need rapid diagnostic tools to narrow antibiotic therapy. Class 1-3 integrons, identified by intI1-3 genes, are genetic elements that play a major role in antibiotic resistance in GNB. OBJECTIVES: The objective of the IRIS study was to evaluate the negative and positive predictive values (NPVs and PPVs, respectively) of intI1-3 as markers of antibiotic resistance. METHODS: The IRIS study was an observational cross-sectional multicentre study that enrolled adult subjects with suspected urinary tract or intra-abdominal infections. intI1-3 were detected directly from routinely collected biological samples (blood, urine or intra-abdominal fluid) using real-time PCR. A patient was considered 'MDR positive' if at least one GNB, expressing acquired resistance to at least two antibiotic families among ß-lactams, aminoglycosides, fluoroquinolones and/or co-trimoxazole, was isolated from at least one biological sample. RESULTS: Over a 2 year period, 513 subjects were enrolled and 409 had GNB documentation, mostly Enterobacterales. intI1 and/or intI2 were detected in 31.8% of patients and 24.4% of patients were considered 'MDR positive'. The NPV of intI1 and/or intI2 as a marker of acquired antibiotic resistances was estimated at 92.8% (89.1%-95.5%). The NPVs for first-line antibiotics were all above 92%, notably >96% for resistance to third-generation cephalosporins. CONCLUSIONS: The IRIS study strongly suggests that the absence of intI1 and intI2 in biological samples from patients with GNB-related infections is predictive of the absence of acquired resistances.

Common variants in glucuronidation enzymes and membrane transporters as potential risk factors for colorectal cancer: a case control study.

BACKGROUND: Associations between polymorphisms of UDP-glucuronosyltransferases (UGTs) or efflux transporters (e.g., P-glycoprotein and MRP2) and different types of cancer have been described, whereas the role of influx transporters (e.g. OATP1B1 and OATP2B1) has been seldom explored. The GenColon study investigated potential associations between variant alleles of UGTs, efflux and influx transporters and CRC. METHODS: Three hundred CRC cases were matched with 300 controls for age, sex and enrolment site. Fifteen SNPs in UGT1A6-9, UGT2B7, ABCB1, ABCC2, SLCO1B1 and SLCO2B1 genes were characterized using Taqman® PCR. Using multivariate conditional logistic regression, we investigated the relationships between CRC and "environmental" risk factors (physical activity, housing and working areas, consumption of red meat, tobacco, alcohol); genetic polymorphisms, in the study population and in the subgroups with "environmental" risk factors. RESULTS: No significant association was observed for the analyzed SNPs (or haplotypes). However, an increased CRC risk was found in carriers of the UGT1A8 rs1042597-G variant allele (additive risk OR = 3.39[1.29-8.89], p = 0.02951) in the subgroup of meat-consumers (n = 84), and in carriers of the ABCB1 rs1045642-T (exon26) variant allele (additive risk; OR = 1.89[1.10-3.39], p = 0.0257) in the "never alcohol consumption subgroup" (n = 125). In addition, as previously reported, the following CRC risk factors were identified: absence of physical activity (OR = 6.35[3.70-10.9], p < 0.0001), living or working in rural or mix area (OR = 2.50[1.48-4.23], p = 0.0006 and OR = 2.99[1.63-5.48], p = 0.004, respectively) and tobacco exposure >30 years (3.37[1.63-6.96], p = 0.0010). CONCLUSIONS: Variant genotypes of influx transporters (OATP1B1 and 2B1) were not associated with CRC. This study confirmed the influence of lifestyle factors, but not the previously reported detrimental effect of SNPs in intestinal UGTs or efflux transporters, except for a UGT1A8 variant in subjects consuming meat and the exon 26 SNP of ABCB1 in the never alcohol consumption subgroup. TRIAL REGISTRATION: Registered in Direction Générale de la Santé the 1st July 2008 under the number DGS2008-0144.

Cytomegalovirus in donors for fecal microbiota transplantation, the phantom menace?

BACKGROUND: Fecal Microbiota Transplantation (FMT) has become the preferred treatment for recurrent Clostridioides difficile Infections (CDI). However, donor screening is a complex process that varies between countries. The primary objective of screening is to prevent the transfer of potential pathogens from the donor to the recipient via feces. Many guidelines recommend Cytomegalovirus (CMV) testing as part of donor screening, but is the risk of CMV transmission well supported by evidence? MATERIALS/METHODS: A French prospective cross-sectional multicenter single-arm study estimated the frequency of detection of CMV in the stool of voluntary healthy donors selected for FMT. All preselected donors were tested for CMV antibodies in blood, and if positive, CMV DNA PCR was performed on whole blood and stool. For samples CMV positive in stool PCR, or case of serological markers positive for IgM, we planned isolation of CMV in cell culture. RESULTS: From June 1, 2016, to July 31, 2017, 500 healthy donors (250 per center) were recruited and 483 included. Of these, 301 were CMV seronegative, and 182 tested positive for CMV IgM and/or IgG. Stool CMV PCR was performed in 162 donors. In two cases, the initial analysis was positive, but below the limit of quantification. Repeated PCR tests using Siemens and Altostar assays were negative. No infectious CMV could be detected in cell culture of these two samples and in the stool of 6 CMV IgM-positive donors. CONCLUSIONS: Our study shows that healthy volunteers with positive CMV serology do not shed CMV DNA in their stool, as detected by PCR or cell culture. This study provides another argument to remove CMV screening for FMT donors.

Attitudes, knowledge, and willingness to be vaccinated against seasonal influenza among patients hospitalized with influenza-like-illness: impact of diagnostic testing.

Influenza vaccine adherence remains low. Communication of virological diagnosis to adults hospitalized with influenza-like illness (ILI) could improve their willingness to be subsequently vaccinated. We prospectively assessed, in adults hospitalized with ILI in six French university hospitals, their willingness to be vaccinated against influenza in the subsequent season, both before and after the communication of RT-PCR Influenza laboratory result; we identified then the determinants associated with the willingness to be vaccinated.A total of 309 patients were included during the 2012-2013 and 2013-2014 influenza seasons; 43.8% reported being vaccinated against influenza for the current season; before communication of influenza laboratory results, 65.1% reported willingness to be vaccinated during the subsequent season. Influenza was virologically confirmed in 103 patients (33.3%). The rate of vaccine willingness increased to 70.4% (p = .02) after communication of influenza laboratory results. Factors independently associated with the willingness to be vaccinated were the perception of influenza vaccine benefits (adjusted relative risk (aRR): 1.06, 95%CI 1.02-1.10), cues to action (aRR: 1.08, 95%CI 1.03-1.12), current season influenza vaccination (aRR: 1.38, 95%CI 1.20-1.59) and communication of a positive influenza laboratory result (aRR: 1.18, 95%CI 1.03-1.34). This last was associated with the willingness to be vaccinated only in the subpopulation of patients not vaccinated (aRR: 1.53, 95%CI 1.19-1.96).In patients hospitalized with ILI, communication of a positive influenza diagnostic led to a better appreciation of the disease's severity and increased the willingness to be vaccinated. This approach might be particularly beneficial in patients who do not have a history of influenza vaccination.

Cytomegalovirus (CMV) Shedding in French Day-Care Centers: A Nationwide Study of Epidemiology, Risk Factors, Centers' Practices, and Parents' Awareness of CMV.

BACKGROUND: Congenital cytomegalovirus (CMV) remains an important healthcare burden, resulting from primary or secondary infection in pregnant women. Exposure to young children's saliva is a major risk factor, as prevalence of CMV shedding can reach 34%. METHODS: This cross-sectional, multicenter, nationwide study was conducted in randomly selected day care centers (DCCs), and complemented with a survey among parents and DCCs. All children aged >3 months were eligible. The study measured the CMV shedding prevalence in children's saliva and described CMV genotypes epidemiology. The risk factors for CMV shedding and high viral load were evaluated using multivariable models. RESULTS: A total of 93 DCCs participated. Among the 1770 enrolled children with evaluable samples, the CMV shedding prevalence was 40% (713/1770, 95% confidence interval, 34.6-46.1), independently associated with children aged between 12 and 18 months, history of CMV infection in ≥1 parents, a mid-level income. Prevalence increased with DCC staff workload and attending children number. Viral load was ≥5 log-copies CMV/mL in 48% (342/713). Risk factors for higher viral load included children aged between 12 and 18 months, and still being breastfed. The most frequent genotype combinations were gB1-gN4c-gH2 (6.9%), gB1-gN2-gH2 (6.3%), gB4a-gN3a-gH1 (6.3%), and gB1-gN3b-gH2 (5,7%). CMV awareness was low in parents: their serological status was unknown by 72% of mothers and 82% of fathers. Only 41% knew something about CMV. CONCLUSIONS: CMV shedding was independently associated with risk factors related to the children, family and DCC. Some of these risk factors may influence prevention strategies, including through an improved information provided to parents. CLINICAL TRIALS REGISTRATION: NCT01704222.

Factors associated with poor outcomes among adults hospitalized for influenza in France: A three-year prospective multicenter study.

BACKGROUND: Influenza is an important cause of serious illness and death, particularly in elderly and high-risk groups. OBJECTIVES: Aim of this study was to identify factors associated with poor outcomes among adults hospitalized in France for laboratory-confirmed seasonal influenza. STUDY DESIGN: Patients hospitalized for influenza were identified in a prospective, multicenter study carried out in French hospitals during three consecutive influenza seasons (2012-2015). Influenza virus infection was confirmed by reverse transcription polymerase chain reaction. Sociodemographic and clinical variables were compared according to the virus type and subtype. Risk factors for complications, intensive care unit (ICU) admission and death were analyzed by backward stepwise logistic regression. RESULTS: The study population consisted of 566 patients, of whom 56% were older than 65 years and 82% had underlying chronic illnesses. Type A influenza viruses infected 422 patients (75%), including subtype H3N2 in 239 patients (57%). The prior vaccine coverage rate was 38%. Complications occurred in 255 patients (45%), consisting mainly of pneumonia (n=143, 30%) and respiratory failure (n=116, 20%). Eighty-three patients (15%) were admitted to an ICU, and the in-hospital mortality rate was 4% (n=21). Sixty-six patients (12%) received oseltamivir. Age over 65 years was the only identified risk factor for complications. Risk factors for ICU admission were an absence of vaccination, no oseltamivir administration before admission, pre-existing chronic respiratory disease, and current smoking. Age over 65 years and ICU admission were risk factors for death. CONCLUSIONS: Older individuals and patients with underlying conditions are most at risk of influenza complications. Vaccination and early oseltamivir administration, both of which are recommended for these patients, appear to reduce ICU admissions.