Potential of omega-3 and conjugated fatty acids to control microglia inflammatory imbalance elicited by obesogenic nutrients.

High-fat diet-induced obesity detrimentally affects brain function by inducing chronic low-grade inflammation. This neuroinflammation is, at least in part, likely to be mediated by microglia, which are the main immune cell population in the brain. Microglia express a wide range of lipid-sensitive receptors and their activity can be modulated by fatty acids that cross the blood-brain barrier. Here, by combining live cell imaging and FRET technology we assessed how different fatty acids modulate microglia activity. We demonstrate that the combined action of fructose and palmitic acid induce Ikßα degradation and nuclear translocation of the p65 subunit nuclear factor kB (NF-κB) in HCM3 human microglia. Such obesogenic nutrients also lead to reactive oxygen species production and LynSrc activation (critical regulators of microglia inflammation). Importantly, short-time exposure to omega-3 (EPA and DHA), CLA and CLNA are sufficient to abolish NF-κB pathway activation, suggesting a potential neuroprotective role. Omega-3 and CLA also show an antioxidant potential by inhibiting reactive oxygen species production, and the activation of LynSrc in microglia. Furthermore, using chemical agonists (TUG-891) and antagonists (AH7614) of GPR120/FFA4, we demonstrated that omega-3, CLA and CLNA inhibition of the NF-κB pathway is mediated by this receptor, while omega-3 and CLA antioxidant potential occurs through different signaling mechanisms.

High incidence of COVID-19 at nursing homes in Madrid, Spain, despite preventive measures.

OBJECTIVE: To assess the impact of COVID-19 at nine nursing homes in Madrid, Spain, during the first wave of COVID-19 infection and lockdown period when preventive measures were taken to avoid transmission among residents. METHODS: Nine hundred forty-two residents and 846 staff members from nine nursing homes participated in the study (April 18 to June 20, 2020). All participants were tested for SARS-CoV-2 in the nasopharynx by PCR and for IgG antibodies detection. Microbiological status at sampling was defined as active infection (positive PCR ± presence of antibodies), past infection (negative PCR + presence of antibodies), or naïve participants (negative PCR + absence of antibodies). RESULTS: Laboratory results helped classify the residents as having active infection (n=224; 23.8%), past infection (n=462; 49.1%), or being naïve (n=256; 27.1%); staff members were actively infected (n=127; 15.1%), had had a past infection (n=290; 34.2%), or were naïve (n=429; 50.7%). Overall, the percentage of participants with COVID-19 was significantly higher in residents than in staff members (72.8% vs 49.2%; P=0.001). The clinical situation of residents vs staff at sampling was as follows: acute manifestations compatible with COVID-19 (7.3% vs 3.9%; P<0.01) and no manifestations of infection (92.7% vs 96.0%; P<0.01). A large proportion of both asymptomatic and symptomatic residents (69.4% vs 86.6%; P=0.015) had positive PCR results (mostly alongside positive IgG determinations). CONCLUSIONS: COVID-19 affects 75% of the residents in nursing homes in Madrid. The high impact in these settings, despite the strict restrictions adopted during the lockdown, demonstrates the ability of SARS-CoV-2 to cause outbreaks.

Bezlotoxumab in the treatment of Clostridioides difficile infections: a real-life experience.

OBJECTIVE: Following the approval of bezlotoxumab in 2017, studies evaluating its effectiveness in prevention of Clostridioides difficile infection under "real-life" conditions are scarce. METHODS: We conducted a retrospective study developed in a large tertiary care hospital describing the use and outcomes of patients with Clostridioides difficile infection (CDI) treated with bezlotoxumab. RESULTS: A total of 16 patients were include, all of whom had an episode of CDI with high probability of recurrence and 14 of them had some kind of immunosuppression. Bezlotoxumab was effective in the prevention of CDI recurrence in 11 of the 14 cases in which follow up was possible, without significant side effects. CONCLUSIONS: Bezlotoxumab was well tolerated and the incidence of recurrent CDI in a high-risk population for recurrence was only 21.4%.

Evaluation of a nationwide Dutch guideline to detect Lynch syndrome in patients with endometrial cancer.

OBJECTIVE: In the Netherlands a nationwide guideline was introduced in 2016, which recommended routine Lynch syndrome screening (LSS) for all women with endometrial cancer (EC) <70 years of age. LSS consists of immunohistochemical (IHC) staining for loss of mismatch repair (MMR) protein expression, supplemented with MLH1 methylation analysis if indicated. Test results are evaluated by the treating gynaecologist, who refers eligible patients to a clinical geneticist. We evaluated the implementation of this guideline. METHODS: From the nation-wide pathology database we selected all women diagnosed with EC < 70 years of age, treated from 1.6.2016-1.6.2017 in 14 hospitals. We collected data on the results of LSS and follow up of cases with suspected LS. RESULTS: In 183 out of 204 tumours (90%) LSS was performed. In 41 cases (22%) MMR protein expression was lost, in 25 cases due to hypermethylation of the MLH1 promotor. One patient was known with a pathogenic MLH1 variant. The option of genetic counselling was discussed with 12 of the 15 remaining patients, of whom three declined. After counselling by the genetic counsellor nine patients underwent germline testing. In two no pathogenic germline variant was detected, two were diagnosed with a pathogenic PMS2 variant, and five with a pathogenic MSH6 variant, in concordance with the IHC profiles. CONCLUSION: Coverage of LSS was high (90%), though referral for genetic counselling could be improved. Gynaecologists ought to be aware of the benefits and possible drawbacks of knowing mutational status, and require training in discussing this with their patients.

Role of Clostridioides difficile in hospital environment and healthcare workers.

Clostridioides difficile infection (CDI) was traditionally considered to be transmitted within healthcare environment, from other patients or healthcare workers (HCW). Recently, this idea has been challenged. Our objective was to determine the extent of C. difficile contamination in hospital environment with a simplified method for C. difficile recovery. Environmental samples were taken from rooms of patients positive for CDI (Case) and negative for toxigenic C. difficile (Control). Environmental sampling was performed at the time a fecal sample was taken for CDI diagnosis, 48 h after, and 10 days after. HCW hands were also sampled. A total of 476 environmental samples were collected, 246 samples from "Case" rooms and 230 from "Control". Overall, 15.34% of environmental samples were positive for toxigenic C. difficile (TCD), 20.72% of "Case" rooms samples and 9.57% of the samples from "Control" rooms (p = 0.001). When samples from "Case" rooms were analyzed by sampling time, at diagnosis 52.94% were positive, 38.46% were positive at 48 h after symptom resolution and 23.07% were positive after course of treatment. Overall, the most contaminated site corresponded to the bathroom tap, followed by the toilet. We recovered TCD from alcohol-based dispensers and from 4.2% of HCW hands. We found a high proportion of surfaces contaminated with TCD, as well as hand colonization. Notably, even after isolation measures were terminated, there was still TCD contamination.

Recommendations for the diagnosis and treatment of Clostridioides difficile infection: An official clinical practice guideline of the Spanish Society of Chemotherapy (SEQ), Spanish Society of Internal Medicine (SEMI) and the working group of Postoperative Infection of the Spanish Society of Anesthesia and Reanimation (SEDAR).

This document gathers the opinion of a multidisciplinary forum of experts on different aspects of the diagnosis and treatment of Clostridioides difficile infection (CDI) in Spain. It has been structured around a series of questions that the attendees considered relevant and in which a consensus opinion was reached. The main messages were as follows: CDI should be suspected in patients older than 2 years of age in the presence of diarrhea, paralytic ileus and unexplained leukocytosis, even in the absence of classical risk factors. With a few exceptions, a single stool sample is sufficient for diagnosis, which can be sent to the laboratory with or without transportation media for enteropathogenic bacteria. In the absence of diarrhoea, rectal swabs may be valid. The microbiology laboratory should include C. difficile among the pathogens routinely searched in patients with diarrhoea. Laboratory tests in different order and sequence schemes include GDH detection, presence of toxins, molecular tests and toxigenic culture. Immediate determination of sensitivity to drugs such as vancomycin, metronidazole or fidaxomycin is not required. The evolution of toxin persistence is not a suitable test for follow up. Laboratory diagnosis of CDI should be rapid and results reported and interpreted to clinicians immediately. In addition to the basic support of all diarrheic episodes, CDI treatment requires the suppression of antiperistaltic agents, proton pump inhibitors and antibiotics, where possible. Oral vancomycin and fidaxomycin are the antibacterials of choice in treatment, intravenous metronidazole being restricted for patients in whom the presence of the above drugs in the intestinal lumen cannot be assured. Fecal material transplantation is the treatment of choice for patients with multiple recurrences but uncertainties persist regarding its standardization and safety. Bezlotoxumab is a monoclonal antibody to C. difficile toxin B that should be administered to patients at high risk of recurrence. Surgery is becoming less and less necessary and prevention with vaccines is under research. Probiotics have so far not been shown to be therapeutically or preventively effective. The therapeutic strategy should be based, rather than on the number of episodes, on the severity of the episodes and on their potential to recur. Some data point to the efficacy of oral vancomycin prophylaxis in patients who reccur CDI when systemic antibiotics are required again.

Faecal microbiota transplantation for recurrent Clostridioides difficile infection: experience with lyophilized oral capsules.

BACKGROUND: Faecal microbiota transplantation (FMT) is a highly effective approach for refractory and recurrent Clostridioides difficile infection (CDI). Despite its excellent efficacy, FMT is not yet a routine procedure in most centres. There is very little experience with FMT based on lyophilized capsules, and data from European institutions are lacking. This article describes our experience with FMT to treat recurrent CDI using lyophilized oral capsules. METHODS: A prospectively recorded single-centre case series of patients with recurrent CDI who underwent FMT between January 2018 and May 2019 were analysed. The primary outcome was defined as resolution of CDI without recurrences over a two-month period. Overall resolution was defined as resolution of diarrhoea without recurrence of CDI within two months after a further cycle of FMT. The FMT process involved oral ingestion of four or five lyophilized capsules in a single dose. All stool donors were rigorously screened. FINDINGS: FMT was performed in 32 patients. Primary cure was achieved in 81.3% of patients, and the overall cure rate was 87.5%. FMT via lyophilized capsules was well tolerated. No FMT procedure-related adverse events and no further complications were observed for lyophilized-capsule FMT. CONCLUSIONS: This initial clinical experience suggests that FMT based on oral lyophilized preparations is a safe, well-tolerated, and highly effective treatment for recurrent CDI. Administration of oral lyophilized capsules seems feasible in hospital routine and will enable FMT to be more widely used.

Clostridioides difficile contamination in a clinical microbiology laboratory?

OBJECTIVES: Clostridioides difficile infection has traditionally been considered to be transmitted predominantly within health-care settings. It is not recognized as a pathogen that presents a risk of laboratory acquisition. Data on laboratory contamination and acquisition by laboratory personnel are lacking. Our objective was to assess environmental contamination by C. difficile and its potential for transmission in a clinical microbiology laboratory. METHODS: Laboratory surfaces were screened for C. difficile. Samples were taken in areas that handle C. difficile isolates (high-exposure (HE) areas), areas adjacent to HE areas or those processing faecal samples (medium-exposure (ME) areas), and areas that do not process faecal samples or C. difficile isolates (low-exposure (LE) areas). We examined C. difficile carriage (hands/rectal samples) of laboratory workers. RESULTS: A total of 140 environmental samples were collected from two HE areas (n = 56), two ME areas (n = 56) and two LE areas (n = 28). Overall, 37.8% (37/98) of surfaces were contaminated with C. difficile, and 17.3% (17/98) with toxigenic C. difficile (TCD). HE areas were significantly more contaminated with TCD than LE areas (38.1% (16/42) versus 0.0% (0/14), p 0.005) and ME areas (38.1% (16/42) versus 2.4% (1/42), p <0.001). Hands were colonized with TCD in 11.8% (4/34) of cases. We found no rectal carriage of C. difficile. CONCLUSIONS: We found a significant proportion of laboratory surfaces to be contaminated with toxigenic C. difficile, as well as hand colonization of laboratory personnel. We recommend specific control measures for high-risk areas and laboratory personnel working in these areas.

Prediction of poor outcome in Clostridioides difficile infection: A multicentre external validation of the toxin B amplification cycle.

Classification of patients according to their risk of poor outcomes in Clostridioides difficile infection (CDI) would enable implementation of costly new treatment options in a subset of patients at higher risk of poor outcome. In a previous study, we found that low toxin B amplification cycle thresholds (Ct) were independently associated with poor outcome CDI. Our objective was to perform a multicentre external validation of a PCR-toxin B Ct as a marker of poor outcome CDI. We carried out a multicentre study (14 hospitals) in which the characteristics and outcome of patients with CDI were evaluated. A subanalysis of the results of the amplification curve of real-time PCR gene toxin B (XpertTM C. difficile) was performed. A total of 223 patients were included. The median age was 73.0 years, 50.2% were female, and the median Charlson index was 3.0. The comparison of poor outcome and non-poor outcome CDI episodes revealed, respectively, the following results: median age (years), 77.0 vs 72.0 (p = 0.009); patients from nursing homes, 24.4% vs 10.8% (p = 0.039); median leukocytes (cells/µl), 10,740.0 vs 8795.0 (p = 0.026); and median PCR-toxin B Ct, 23.3 vs 25.4 (p = 0.004). Multivariate analysis showed that a PCR-toxin B Ct cut-off <23.5 was significantly and independently associated with poor outcome CDI (p = 0.002; OR, 3.371; 95%CI, 1.565-7.264). This variable correctly classified 68.5% of patients. The use of this microbiological marker could facilitate early selection of patients who are at higher risk of poor outcome and are more likely to benefit from newer and more costly therapeutic options.

Diversity of Staphylococcus aureus clones in wild mammals in Aragon, Spain, with detection of MRSA ST130-mecC in wild rabbits.

AIMS: To determine the Staphylococcus aureus carriage rate in wild mammals in Aragon, northern Spain, to analyse their antimicrobial resistance phenotype/genotype and to characterize the recovered isolates. METHODS AND RESULTS: Nasal and rectal swabs of 103 mammals were collected in Aragón during the period 2012-2015. Antimicrobial susceptibility, the presence of antimicrobial resistance genes and virulence factors were investigated. Molecular characterization was carried out by spa, MLST, agr and SCCmec. Staphylococcus aureus were recovered from 23 animals (22%). Four of the 23 S. aureus were methicillin-resistant S. aureus (MRSA). Three MRSA were mecC-positive and were isolated from European rabbits and were typed as t843 (ascribed to CC130). The remaining MRSA was a mecA-carrying isolate from European hedgehog, typed as ST1-t386-SCCmecIVa-agrIII and it harboured the blaZ, erm(C), ant(6)-Ia and aph(3´)-IIIa resistance genes. A high diversity of spa-types was detected among the 19 methicillin-susceptible S. aureus isolates, which showed high susceptibility to the antimicrobials tested. The tst gene and different combinations of staphylococcal enterotoxins were found. CONCLUSIONS: Staphylococcus aureus were detected in nasal and rectal samples of wild mammals. Wild rabbits could be a reservoir of mecC-MRSA. SIGNIFICANCE AND IMPACT OF THE STUDY: This work provides information on the presence and characteristics of S. aureus from mammals in a defined geographic region in Spain.

Associations between urinary organophosphate ester metabolites and measures of adiposity among U.S. children and adults: NHANES 2013-2014.

BACKGROUND: Organophosphate esters (OPEs) are synthetic chemicals found in many consumer products, including furniture, electronics, processed foods, and building materials. Emerging in vitro and in vivo studies suggest that OPEs are metabolism disrupting compounds; however, epidemiologic studies investigating their associations with adiposity markers are sparse. OBJECTIVE: We examined cross-sectional associations between OPE biomarkers and adiposity measures among U.S. children and adults participating in the National Health and Nutrition Examination Survey (NHANES: 2013-2014). METHODS: Concentrations of five OPE metabolites were quantified in urine: diphenyl phosphate (DPHP), bis(1,3-dichloro-2-propyl) phosphate (BDCPP), bis(2-chloroethyl) phosphate (BCEP), dibutyl phosphate (DBUP), and bis(1-chloro-2-propyl) phosphate (BCPP). We conducted covariate-adjusted logistic and linear regressions to examine associations between log2-transformed and dichotomized OPE metabolite concentrations and obesity, body mass index (BMI), and waist circumference (WC), separately among 784 children (6-19 years) and 1672 adults (≥20 years). We also assessed heterogeneity of associations by sex. RESULTS: DBUP concentrations were inversely associated with the prevalence odds of being obese vs. normal weight in children (adjusted Prevalence Odds Ratio, aPOR: 0.82, 95% Confidence Interval, 95% CI: 0.70, 0.95) and adults (aPOR: 0.83, 95% CI: 0.72, 0.96). DBUP was also significantly associated with lower BMI z-scores (ß:-0.08, 95% CI:-0.17, 0.01) and WC (ß:-0.71, 95% CI: -1.49, 0.07) in children. BCEP concentrations were associated with increased prevalence odds of being overweight vs. normal weight (aPOR: 1.15, 95% CI: 1.01, 1.32) among children; similar, albeit not statistically significant, relationships were observed with other child adiposity outcomes. Among adults, detectable BCPP concentrations were associated with increased prevalence odds of being obese vs. normal weight (aPOR: 1.70, 95% CI: 1.21, 2.38) and having a high vs. normal WC (aPOR: 1.51, 95% CI: 1.11, 2.07) as well as higher BMI (ß: 1.31, 95% CI: 0.30, 2.33). Other OPE metabolites were not consistently associated with adiposity measures among adults. Although associations of BCPP exposure with adiposity outcomes were generally inverse among boys, but not girls, we did not observe consistent evidence of sexually-dimorphic associations for other OPE metabolites. CONCLUSIONS: Exposure to select OPEs may be differentially associated with body size among children and adults. Given the cross-sectional design of the present study, future prospective studies are needed to confirm these findings.

Fecal microbiota transplantation for recurrent Clostridium difficile infection: Experience, protocol, and results.

OBJECTIVE: Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent Clostridium difficile infection (R-CDI). Despite its excellent efficacy, it is still not a routine procedure in most European centers. FMT has not been widely used in Spain to date. We describe our experience with FMT, including a novel approach based on oral fecal capsules. METHODS: We analyzed a prospectively recorded case series of patients with R-CDI treated with FMT at a single center (June 2014-July 2017). Primary outcome was defined as resolution of CDI without recurrence in a two-month period. FMT was administered via colonoscopy, nasojejunal tube, or oral capsules. All stool donors were rigorously screened. RESULTS: FMT was performed in 13 patients with R-CDI. Median age was 75.0 years and 76.9% were females. Six FMT were performed via nasojejunal tube, 5 via oral capsules, and 2 by colonoscopy. There were no procedure-related adverse events, except for bacteremia in one patient. During follow-up, R- CDI was observed in one patient at one month after FMT. The primary resolution rate was 83.3% and the overall resolution rate was 91.7%. FMT by capsules achieved a 100% resolution rate, colonoscopy 100%, and nasojejunal tube 80.0%. CONCLUSIONS: In our cohort, FMT proved to be safe and effective, even in high risk patients. Oral administration in capsules also proved to be safe, well-tolerated, and highly effective for R-CDI. In our experience, the FMT capsule formulation seems feasible in the routine of a hospital. This administration method will allow FMT to be more widely used.

Direct identification of clinical pathogens from liquid culture media by MALDI-TOF MS analysis.

OBJECTIVES: We propose using MALDI-TOF MS as a tool for identifying microorganisms directly from liquid cultures after enrichment of the clinical sample in the media, to obtain a rapid microbiological diagnosis and an adequate administration of the antibiotic therapy in a clinical setting. METHODS: To evaluate this approach, a series of quality control isolates were grown in thioglycollate (TG) broth and brain heart infusion (BHI) broth and extracted under four different protocols before finally being identified by MALDI-TOF MS. After establishing the best extraction protocol, we validated the method in a total of 300 liquid cultures (150 in TG broth and 150 in BHI broth) of different types of clinical samples obtained from two tertiary Spanish hospitals. RESULTS: The initial evaluation showed that the extraction protocol including a 5 minute sonication step yielded 100% valid identifications, with an average score value of 2.305. In the clinical validation of the procedure, 98% of the microorganisms identified from the TG broth were correctly identified relative to 97% of those identified from the BHI broth. In 24% of the samples analysed, growth by direct sowing was only successful in the liquid medium, and no growth was observed in the direct solid agar cultures. CONCLUSIONS: Use of MALDI-TOF MS plus the sonication-based extraction method enabled direct and accurate identification of microorganisms in liquid culture media in 15 minutes, in contrast to the 24 hours of subculture required for conventional identification, allowing the administration of a targeted antimicrobial therapy.

[Factor associated in the failure of the ostheosyntesis of transtrocantheric fractures]. / Factores asociados a fallo en la osteosíntesis de fracturas transtrocantéricas.

Pertrochanteric fractures account approximately a half of the proximal femoral fractures. Incidence of these fractures is highest in women, age > 65 years and presents a mortality rate of 14 to 50%. Treatment goals include stable fixation, immediate mobilization and restore activities. Complications after treatment present in 17% and include: nonunion, cut out and varus displacement. OBJECTIVE: Correlation between complications after surgical treatment and presence of instability, inadequate reduction, Tip Apex Index (TAI) > 25 mm, Tip Apex Index to calcar (TAIcal) > 20 mm and parker index. MATERIAL AND METHODS: A case control study was conducted in patients with pertrochanteric fractures treated between January 2009 and December 2014, 91 patients were included and complications were measured up to 6 months after surgery. RESULTS: 27 patients were included in group 1, which were the ones who presented complications. Values of TAI measured in this group were 13.7 to 45 mm, and were significantly higher than group 2. Position of the blade/screw central in the lateral view and inferior in the AP view didn´t present complications. CONCLUSIONS: We found 27 patients with complications in the follow up (29%). Initial reduction and stability is determinant to success. We recommend the use of proximal femoral nail in all unstable fractures. It is confirmed that TAI > 25 mm as a predictor of failure.

Las fracturas transtrocantéricas representan la mitad de las fracturas del fémur proximal. La mayor incidencia es en > 65 años, mujeres y presentan mortalidad al año del 14 al 50%. Los objetivos de tratamiento son: fijación estable, restaurar la movilidad y recuperar la función. Las complicaciones tienen una incidencia de 17%, siendo las más comunes: desplazamiento en varo, no unión y cut out. Objetivo: Evaluar la asociación entre falla de la osteosíntesis y los siguientes factores: mala reducción, inestabilidad, índice punta ápice > (TAI) 25 mm, punta ápice modificado al calcar (TAICal) > 20 mm e índice de Parker. Material y métodos: Se realizó un estudio de casos y controles anidado en una cohorte de pacientes con fracturas transtrocantéricas. De enero del 2009 a diciembre del 2014, se incluyeron 91 pacientes que cumplieron los criterios de selección. El seguimiento se hizo a 6 meses para valorar complicaciones. Resultados: Se incluyeron en el grupo 1 a 27 pacientes que presentaron falla y en el grupo 2 a 64 pacientes. Se obtuvieron en el grupo 1 valores de TAI 13.7 a 45 mm y en el grupo 2 valores de 11 a 31.2 mm. Se encontró que la posición central en lateral e inferior en AP no presentó fallo. Conclusiones: Se encontraron 27 pacientes con complicaciones (29%). La estabilidad inicial es un factor determinante, se recomienda fijación con CCM en los casos de fracturas inestables. Se confirmó la validez de un TAI > 25 mm como un predictor de fallo.

Rifaximin-resistant Clostridium difficile strains isolated from symptomatic patients.

BACKGROUND: Rifaximin has been proposed as an alternative treatment for specific cases of Clostridium difficile infection (CDI) and intestinal decontamination. Rifaximin-resistant C. difficile has occasionally been reported. Antibiotic susceptibility testing relies on anaerobic agar dilution (reference method), which is cumbersome and not routinely used. There is no commercial test for detection of resistance to rifaximin. OBJECTIVES: To assess resistance to rifaximin by C. difficile and to evaluate the correlation between the results of the rifampicin E-test and susceptibility to rifaximin. METHODS: We compared the in vitro susceptibility of clinical CDI isolates to rifaximin over a 6-month period using the agar dilution method with susceptibility to rifampicin using the E-test. All isolates were characterized using PCR-ribotyping. Clinical data were recorded prospectively. RESULTS: We recovered 276 consecutive C. difficile isolates and found that 32.2% of episodes were caused by rifaximin-resistant strains. The MICs for rifaximin ranged from <0.0009-256 mg/L, with a geometric mean (GM) of 0.256 mg/L, an MIC50/90 of 0.015/>256 mg/L. Rifaximin and rifampicin MICs were comparable, and all strains classed as resistant by agar dilution were correctly classified as resistant by E-test. The most common ribotypes were 001 (37.2%), 078/126 (14.3%), and 014 (12.0%). Ribotype 001 exhibited the highest MICs for rifaximin. CONCLUSIONS: Resistance to rifaximin was common; resistance rates were higher in ribotype 001 strains. Susceptibility to rifaximin determined by agar dilution correlated with susceptibility to rifampicin determined using the E-test, including rifaximin-resistant strains. Our results suggest that the rifampicin E-test is a valid method for the prediction of rifaximin-resistant C. difficile.

An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for recurrence and a novel treatment strategy.

An outbreak of Clostridium difficile infection (CDI) caused by ribotype 027 (B1/NAP1) began in our hospital in November 2014, and produced 141 episodes in the following months. The aim of this study is to describe this outbreak, assess risk factors for recurrence of CDI-027 and to analyze the implementation of a novel treatment strategy. This is a prospective study of all patients with CDI-027, from November 2014 to November 2015. The epidemiological data were collected daily for each patient. We compared clinical characteristics and treatment between patients with and without recurrence of CDI-027. Interestingly, liver cirrhosis was present in 22% of the patients, and most of them received prophylaxis for hepatic encephalopathy with rifaximin. Patients were also taking antimicrobial drugs (93.6%) and proton pump inhibitors (80.1%). Overall, 27 (23.5%) patients had a first recurrence of CDI-027. Liver cirrhosis increased the risk of recurrence (44.4% vs 14.8%). Patients treated with a prolonged oral vancomycin regimen vs the conventional regimen (oral metronidazole or 10 days of vancomycin) had fewer recurrences (8.6 versus 44.7% [p ≤ 0.01]; OR, 0.91; 95% CI, 0.028-0.294) and less attributable mortality (0% versus 7.1%; p = 0.058). We report an outbreak of CDI-027, mainly in patients with liver cirrhosis. Recurrence of CDI-027 was more common in those patients. A novel approach involving high-dose prolonged vancomycin taper as a first-line treatment, together with a bundle of outbreak measures, seemed to reduce the number of cases of CDI-027, recurrences, and attributable mortality. Nevertheless, this approach warrants further investigation.

Clinical, immunological and microbiological predictors of poor outcome in Clostridium difficile infection.

BACKGROUND: Clostridium difficile infection (CDI) causes increased morbidity and mortality. Clinical data cannot clearly predict poor CDI outcome. Data on the value of microbiological predictors is scarce. OBJECTIVE: To identify early predictors of poor outcome of CDI. METHODS: We prospectively included patients with CDI aged >2years. Clinical, immunological (Toxin B IgG/Ig A and Toxin A IgG/Ig A), microbiological factors (bacterial load, toxin quantification, sporulation, germination, and metronidazole susceptibility) were evaluated to identify early independent predictors of poor outcome. RESULTS: We identified 204 cases of CDI; outcome was poor in 22.1%. Advanced age, presence of comorbidities, leukocytosis and high toxigenic C. difficile load were independently associated with poor outcome. We could not demonstrate this correlation for antitoxin antibodies. CONCLUSION: We identified high bacterial load as a microbiological predictor of poor outcome. We propose this factor to be included in combined clinical and microbiological prediction rules of poor outcome in CDI.

C. difficile PCR-ribotype 023 might go undetected when using ChromId C. difficile agar.

We compared the performance of the new chromogenic medium ChromID C. difficile with that of CLO agar. ChromID C. difficile agar is a sensitive medium that can accelerate the presumptive identification of C. difficile, however ribotype 023 might go undetected when using this chromogenic medium.