RESUMEN
BACKGROUND: Recurrent Clostridioides difficile infection (rCDI) occurs frequently, and concomitant antibiotic (CA) during the initial episode for treatment of non-CDI is a major risk factor. We sought to address the comparative efficacy of fidaxomicin versus vancomycin in the setting of CA during the initial CDI episode. METHODS: We conducted a randomized, controlled, open-label trial at 2 hospitals in Ann Arbor, Michigan. We consecutively consented and enrolled hospitalized patients ≥18 years old with diarrhea, a positive test for C. difficile, and ≥1 qualifying CA. Complicated CDI, CDI treatment for >24 hours prior to enrollment, and planned long-term (>12 weeks) CA use were notable exclusions. Clinical cure was defined as resolution of diarrhea for 2 consecutive days maintained until 2 days after therapy, and rCDI as recurrent diarrhea with positive testing ≤30 days after initial treatment. Patients were randomized to fidaxomicin or vancomycin. RESULTS: Baseline characteristics were similar in the 2 groups of 144 patients. Rates of clinical cure (73% vs 62.9%, P = .195) and rCDI (3.3% vs 4.0%; P > .99) were similar for fidaxomicin and vancomycin in the intention-to-treat and per-protocol cohorts, respectively. Only 4 patients developed rCDI. CONCLUSIONS: In this study of patients with CDI receiving CA, a numerically higher proportion were cured with fidaxomicin versus vancomycin, but this result did not reach statistical significance. Overall recurrence was lower than anticipated in both arms compared with previous studies that did not extend duration of CDI treatment during CA. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov (NCT02692651).
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Humanos , Adolescente , Antibacterianos/uso terapéutico , Vancomicina/uso terapéutico , Fidaxomicina/uso terapéutico , Aminoglicósidos/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/inducido químicamente , Diarrea/tratamiento farmacológicoRESUMEN
BACKGROUND: Newer antibiotics that specifically target Clostridioides difficile while preserving the host microbiome have emerged to treat C. difficile infection (CDI): cadazolid, fidaxomicin, ridinilazole, and surotomycin. The aim of the present study was to perform a systematic review and meta-analysis of efficacy for each antibiotic. METHODS: Only randomized clinical trials of patients being treated for Clostridioides disease infection were included. Studies were sought in MEDLINE, EMBASE, the Cochrane Register of Controlled Trials, ClinicalTrials.gov, and the World Health Organization clinical trials register portal (up to December 9, 2022). Sustained clinical cure was the outcome of treatment comparison, defined as the resolution of diarrhea without recurrence. Vancomycin was the standard treatment comparator. Meta-analysis was performed for each antibiotic. The overall certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE)-classified as either high, moderate, low, or very low. RESULTS: Fourteen eligible studies were included in the meta-analysis with 4837 patients from 773 sites. Cadazolid did not increase sustained clinical cure relative to vancomycin (risk ratio (RR) 1.04, 95% confidence intervals (CI) 0.96-1.13; moderate-certainty evidence). Fidaxomicin demonstrated a significant increase (RR 1.14, 95% CI 1.07-1.21; low-certainty evidence). In one phase 2 study, ridinilazole demonstrated a significant increase in sustained clinical cure (RR 1.71, 95% CI 1.01-2.91; very low-quality evidence). Surotomycin did not show significant improvement (RR 1.05, 95% CI 0.96-1.14; moderate-certainty evidence). CONCLUSIONS: Fidaxomicin (in seven studies) demonstrated significant improvement in achieving sustained clinical cure. A limitation of this study may that more studies are needed to compare fidaxomicin with other antibiotics.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Humanos , Antibacterianos/uso terapéutico , Vancomicina/uso terapéutico , Fidaxomicina/uso terapéutico , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/inducido químicamenteRESUMEN
WHAT IS ALREADY KNOWN: â¢The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. â¢Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: â¢The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. â¢The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Trazodona , Humanos , Mirtazapina/uso terapéutico , Trazodona/uso terapéutico , Nortriptilina/efectos adversos , Fluoxetina/uso terapéutico , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/epidemiología , Antidepresivos/efectos adversos , HospitalesRESUMEN
BACKGROUND: There are uncertainties regarding associations of prior proton pump inhibitor (PPI) use with susceptibility for COVID-19 and risks associated with SARS-CoV-2 infection. We aimed to evaluate the associations of prior PPI use with outcomes in hospitalized patients with COVID-19. RESEARCH DESIGN AND METHODS: We have retrospectively evaluated a total of 5959 consecutively hospitalized patients with COVID-19 from a tertiary-level institution in the period 3/2020-6/2021. Associations of prior PPI use with outcomes of in-hospital mortality, mechanical ventilation, intensive care unit stay, venous thromboembolism, arterial thrombosis, major bleeding, bacteremia, and Clostridioides difficile infection (C. diff.) were evaluated in entire and case-matched cohorts. RESULTS: Among 5959 evaluated patients, there were 1967 (33%) PPI users. In an entire cohort, prior PPI use was associated with higher in-hospital mortality and higher occurrence of C. diff. Association of prior PPI use with mortality diminished, whereas association with C. diff. persisted after multivariable adjustments. In a matched cohort, prior PPI use was associated only with higher risk of C. diff. but not other outcomes in line with multivariable analysis. CONCLUSIONS: Although prior PPI use might not have a significant impact on clinical course and mortality of SARS-CoV-2 infection, it may predispose patients to the development of complications like higher occurrence of C. diff. and thus substantially impact the course of treatment.
Asunto(s)
COVID-19 , Clostridioides difficile , Infecciones por Clostridium , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Estudios Retrospectivos , SARS-CoV-2 , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/tratamiento farmacológico , HospitalizaciónRESUMEN
The literature regarding Clostridioides difficile infection (CDI) in left ventricular assist devices (LVADs) patients is limited. Therefore, we aimed to characterize the clinical course, risk factors, management, and outcomes of LVAD patients who developed CDI. Adult patients who underwent LVAD placement during 2010-2022 and developed CDI were included. To determine risk factors and outcomes, we matched CDI patients with LVAD patients who did not develop CDI. Each CDI case was matched with up to two control subjects by age, sex, and time from LVAD implantation. Forty-seven of 393 LVAD patients (12.0%) developed CDI. The median time from LVAD implantation to CDI was 147 days (interquartile range 22.5-647.0). The most common CDI treatment was oral vancomycin (n = 26, 55.3%). Thirteen patients (27.7%) required treatment extension because of a lack of clinical response. Three patients (6.4%) developed recurrent CDI. When 42 cases were matched to 79 control subjects, antibiotic exposure within 90 days was significantly associated with CDI (adjusted odds ratio 5.77; 95% confidence interval, 1.87-17.74; p = 0.002). Moreover, CDI was associated with 1 year mortality (adjusted hazard ratio 2.62; 95% confidence interval, 1.18-5.82; p = 0.018). This infection occurs most often within the first year after LVAD implantation and was associated with 1 year mortality. Antibiotic exposure is an important risk for CDI.
Asunto(s)
Infecciones por Clostridium , Corazón Auxiliar , Adulto , Humanos , Corazón Auxiliar/efectos adversos , Estudios Retrospectivos , Antibacterianos/uso terapéutico , Infecciones por Clostridium/etiología , Infecciones por Clostridium/inducido químicamente , Factores de RiesgoRESUMEN
OBJECTIVE: The aim of this study was to analyze and identify documented infections and possible risk factors for Clostridioides difficile infections in children with cancer. METHODS: This is a retrospective case-control study, carried out in a pediatric cancer hospital, covering the years 2016-2019. Matching was performed by age and underlying disease, and for each case, the number of controls varied from 1 to 3. Logistic regression models were used to assess risk factors. RESULTS: We analyzed 63 cases of documented infection by C. difficile and 125 controls. Diarrhea was present in all cases, accompanied by fever higher than 38°C in 52.4% of the patients. Mortality was similar among cases (n=4; 6.3%) and controls (n=6; 4.8%; p=0.7). In all, 71% of patients in the case group and 53% in the control group received broad-spectrum antibiotics prior to the infection. For previous use of vancomycin, the Odds Ratio for C. difficile infection was 5.4 (95% confidence interval [95%CI] 2.3-12.5); for meropenem, 4.41 (95%CI 2.1-9.2); and for cefepime, 2.6 (95%CI 1.3-5.1). For the antineoplastic agents, the Odds Ratio for carboplatin was 2.7 (95%CI 1.2-6.2), melphalan 9.04 (95%CI 1.9-42.3), busulfan 16.7 (95%CI 2.1-134.9), and asparaginase 8.97 (95%CI 1.9-42.9). CONCLUSIONS: C. difficile symptomatic infection in children with cancer was associated with previous hospitalization and the use of common antibiotics in cancer patients, such as vancomycin, meropenem, and cefepime, in the last 3 months. Chemotherapy drugs, such as carboplatin, melphalan, busulfan, and asparaginase, were also risk factors.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Neoplasias , Humanos , Niño , Estudios de Casos y Controles , Estudios Retrospectivos , Vancomicina , Cefepima/uso terapéutico , Meropenem , Busulfano/uso terapéutico , Melfalán/uso terapéutico , Asparaginasa/uso terapéutico , Instituciones Oncológicas , Carboplatino/uso terapéutico , Infección Hospitalaria/epidemiología , Infección Hospitalaria/inducido químicamente , Infección Hospitalaria/tratamiento farmacológico , Antibacterianos/uso terapéutico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/tratamiento farmacológico , Neoplasias/complicaciones , Factores de RiesgoRESUMEN
OBJECTIVE: To determine the risk and prognostic factors for Clostridioides difficile infection (CDI). PATIENTS AND METHODS: Prospective, case-control study with 61 cases and 64 controls, aged ≥2 years with diarrhoea, carried out in Castilla-La Mancha Health Care Area for 14 months. The diagnosis was made by immunochromatography technics (glutamate dehydrogenase and toxin A/B), confirming discordant cases by isothermal amplification. Demographic variables, comorbidities, type of acquisition, previous administration of antibiotics, antacids and immunosuppressants, and evolution were collected. The data were analysed using the chi-square test and the effect of risk and prognostic factors was quantified using an odds ratio with 95% confidence intervals. RESULTS: Hospital admission 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics were identified as independent risk factors for CDI. Presenting these 3 factors constitutes nearly 3-fold increase in the risk of becoming infected. A greater number of hospital admissions in the 4-12 weeks prior to CDI were found in the group of nosocomial acquisition. Although there was a greater tendency to recurrence and an unfavourable prognosis among nosocomial cases, these differences were not significant. We found that fever and hospital admission in the 4 weeks prior to infection were unfavourable prognostic factors of CDI. CONCLUSIONS: The independent risk factors for CDI were: Hospital admission in the 4 weeks prior to infection, hypoalbuminemia, and previous administration of antibiotics. Fever and hospitalisation in the previous 4 weeks were also identified as prognostic factors of unfavourable evolution.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Hipoalbuminemia , Humanos , Estudios de Casos y Controles , Clostridioides , Estudios Prospectivos , Salud Rural , Infección Hospitalaria/epidemiología , Infección Hospitalaria/tratamiento farmacológico , Antibacterianos/uso terapéutico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/inducido químicamente , Estudios RetrospectivosRESUMEN
Antibiotic exposure is a crucial risk factor for community-acquired Clostridioides difficile infection (CA-CDI). However, the relative risks associated with specific antibiotics may vary over time, and the absolute risks have not been clearly established. This is a retrospective cohort study. Adults were included if they received an outpatient antibiotic prescription within the IBM MarketScan databases between 2008 and 2020. The primary exposure was an outpatient antibiotic prescription, and the receipt of doxycycline was used as the reference comparison. The primary outcome was CA-CDI, defined as the presence of an International Classification of Diseases (ICD) diagnosis code for CDI within 90 days of receiving an outpatient antibiotic prescription, and subsequent treatment for CDI. There were 36,626,794 unique patients who received outpatient antibiotics, including 11,607 (0.03%) who developed CA-CDI. Relative to doxycycline, the antibiotics conferring the highest risks for CA-CDI were clindamycin (adjusted odds ratio [aOR], 8.81; 95% confidence interval [CI], 7.76 to 10.00), cefdinir (aOR, 5.86; 95% CI, 5.03 to 6.83), cefuroxime (aOR, 4.57; 95% CI, 3.87 to 5.39), and fluoroquinolones (aOR, 4.05; 95% CI, 3.58 to 4.59). Among older patients with CA-CDI risk factors, nitrofurantoin was also associated with CA-CDI (aOR, 3.05; 95% CI, 1.92 to 4.84), with a smaller number needed to harm, compared to the fluoroquinolones. While clindamycin, cefuroxime, and fluoroquinolone use declined from 2008 to 2020, nitrofurantoin use increased by 40%. Clindamycin was associated with the greatest CA-CDI risk, overall. Among older patients with an elevated baseline risk for CA-CDI, multiple antibiotics, including nitrofurantoin, had strong associations with CA-CDI. These results may guide antibiotic selection and future stewardship efforts.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Infección Hospitalaria , Adulto , Humanos , Estados Unidos/epidemiología , Antibacterianos/efectos adversos , Doxiciclina , Estudios Retrospectivos , Clindamicina/efectos adversos , Nitrofurantoína , Cefuroxima , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Infecciones por Clostridium/inducido químicamente , Fluoroquinolonas , Factores de Riesgo , Infección Hospitalaria/tratamiento farmacológicoRESUMEN
PURPOSE: There is a lack of real-world evidence of the comparative effectiveness of fidaxomicin versus vancomycin or metronidazole for treating patients with Clostridium difficile (CDI) infection. No systematic evidence comparing these treatment regimens using real-world observational studies was published up to date. The goal of this study is to compare the fidaxomicin and vancomycin/metronidazole regimens in terms of treatment outcomes in CDI patients. METHODS: Systematic and comprehensive search was carried out in the following databases and search engines: EMBASE, Cochrane, MEDLINE, ScienceDirect, and Google Scholar from 1954 until January 2022. Newcastle-Ottawa (NO) scale was used to assess the risk of bias. Meta-analysis was carried out using random effects model, and pooled odds ratios (OR) with 95% confidence interval (CI) were reported. RESULTS: A total of 10 studies satisfied the inclusion criteria, most of them were with poorer quality. The pooled OR was 0.40 (95% CI: 0.09-1.68; I2 = 82.4%) for clinical cure and 2.02 (95% CI: 0.36-11.39; I2 = 88.4%) for sustained cure. We reported pooled OR of 0.69 (95% CI: 0.40-1.20; I2 = 65.7%) for the recurrence rate, 2.81 (95% CI: 1.08-7.29; I2 = 70.6%) for the treatment failure, and 0.73 (95% CI: 0.50-1.07; I2 = 0%) for all-cause mortality between patients that received fidaxomicin and vancomycin. The pooled OR was 0.71 (95% CI: 0.05-9.47; I2 = 69.6%) in terms of recurrence between patients receiving fidaxomicin and metronidazole. CONCLUSION: Fidaxomicin and vancomycin/metronidazole regimens did not have significant difference in terms of treatment outcomes, such as clinical cure, sustained cure, recurrence, and all-cause mortality. However, there was significantly higher risk of treatment failure in CDI patients taking fidaxomicin.
Asunto(s)
Infecciones por Clostridium , Enterocolitis Seudomembranosa , Aminoglicósidos/uso terapéutico , Antibacterianos/uso terapéutico , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/tratamiento farmacológico , Enterocolitis Seudomembranosa/inducido químicamente , Enterocolitis Seudomembranosa/tratamiento farmacológico , Fidaxomicina/uso terapéutico , Humanos , Metronidazol/uso terapéutico , Vancomicina/uso terapéuticoRESUMEN
BACKGROUND AND OBJECTIVE: Immune-mediated diarrhea and colitis (IMDC) is a common adverse event in cancer patients receiving immune checkpoint inhibitors (ICIs). Gastrointestinal (GI) infections can co-occur with IMDC, and its impact on the course and outcome of IMDC remains unclear. PATIENTS AND METHODS: We retrospectively reviewed cancer patients who received ICIs and developed IMDC between January 2015 and September 2019. GI multiplex panel is used to assess GI infection. The study group included patients with positive infection except those who are only positive for Clostridioides difficile or cytomegalovirus. The control group is IMDC patients with negative infection using frequency matching. Patients' disease course and outcome were compared between groups. RESULTS: A total of 72 patients with IMDC were included: 22 in the study group and 50 as control. Escherichia coli of different pathotypes was observed in 17 patients. Five patients had viral infections, for example, adenovirus, norovirus, and sapovirus. Patients with GI infections more frequently had grade 3 or 4 colitis (43% vs. 18%, P=0.041). Overall, GI infections were not associated with different risks of IMDC recurrence or overall survival. Antibiotics treatment did not affect the requirement for infliximab or vedolizumab but relate to a higher risk of IMDC recurrence (50.0% vs. 0.0%, P=0.015). CONCLUSIONS: In our study, concomitant GI infections are associated with more severe symptoms in IMDC patients. Antimicrobial treatment did not circumvent the need for immunosuppressive therapy for IMDC or improve the clinical outcome. Concomitant GI infection was not associated with a higher risk of IMDC recurrence or poor overall survival.
Asunto(s)
Colitis/inducido químicamente , Diarrea/inducido químicamente , Enfermedades Gastrointestinales/microbiología , Enfermedades Gastrointestinales/virología , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Anciano , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Infecciones por Clostridium/inducido químicamente , Colitis/mortalidad , Colitis/terapia , Diarrea/mortalidad , Diarrea/terapia , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/etiología , Femenino , Enfermedades Gastrointestinales/tratamiento farmacológico , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/microbiología , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Virosis/etiología , Virosis/virologíaRESUMEN
BACKGROUND: Proton-pump inhibitors (PPIs) have been reported to increase the risk of community-associated Clostridium difficile infection (CDI), but the association remains disputed. METHODS: A nationwide cohort study among adults in Denmark, 2010-2013, linking register data on C. difficile testing, filled prescriptions, and patient characteristics. All incident episodes of community-associated CDI (ie, positive culture, molecular assay, or toxin test in individuals without previous hospitalization in the prior 12 weeks and without a positive test for C. difficile in the prior 8 weeks) were identified in the Danish National Microbiological Database. Self-controlled case-series analyses were used to estimate incidence rate ratios (IRRs) for community-associated CDI, comparing periods with and without exposure to PPIs. By design, models took fixed confounders such as chronic disease, genetics, and socioeconomic status into account; further, time-varying confounders, including hospital stay and antibiotic and corticosteroid use were adjusted for. RESULTS: 3583 episodes of community-associated CDI were identified, of which 964 occurred during current use of PPIs, 324 occurred 0-6 months after treatment cessation, 123 occurred 6-12 months after treatment cessation, and 2172 occurred during time periods without use of PPIs. The adjusted IRR was 2.03 (95% confidence interval, 1.74-2.36), comparing use of PPI with nonuse. The increased risk remained elevated in later time periods: 1.54 (1.31-1.80) for 0-6 months, 1.24 (1.00-1.53) for 6-12 months after current use. CONCLUSIONS: Use of PPIs was associated with moderately increased risk of community-associated CDI. The risk remained elevated up to 1 year after PPI treatment had ended.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Enterocolitis Seudomembranosa , Adulto , Antibacterianos/uso terapéutico , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/tratamiento farmacológico , Infecciones por Clostridium/epidemiología , Estudios de Cohortes , Enterocolitis Seudomembranosa/tratamiento farmacológico , Humanos , Inhibidores de la Bomba de Protones/efectos adversos , Factores de RiesgoRESUMEN
PURPOSE OF REVIEW: To explore the evidence for an association between penicillin allergy, antibiotic prescribing and Clostridioides difficile (CDI) infection. RECENT FINDINGS: Several studies have highlighted the differences in antibiotic prescribing in penicillin allergic patients and the impact on rates of C. difficile infection. SUMMARY: Penicillin allergy leads to higher incidences of prescriptions for antibiotics that are known to predispose to CDI. In turn CDI is more common in patients with penicillin allergy. Penicillin allergy is often erroneously ascribed to patients and should be challenged.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium , Hipersensibilidad a las Drogas , Hipersensibilidad , Penicilinas , Clostridioides , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/epidemiología , Hipersensibilidad a las Drogas/complicaciones , Humanos , Penicilinas/efectos adversosRESUMEN
BACKGROUND & AIMS: Clostridioides difficile toxin A (TcdA) activates the innate immune response. TcdA co-purifies with DNA. Toll-like receptor 9 (TLR9) recognizes bacterial DNA to initiate inflammation. We investigated whether DNA bound to TcdA activates an inflammatory response in murine models of C difficile infection via activation of TLR9. METHODS: We performed studies with human colonocytes and monocytes and macrophages from wild-type and TLR9 knockout mice incubated with TcdA or its antagonist (ODN TTAGGG) or transduced with vectors encoding TLR9 or small-interfering RNAs. Cytokine production was measured with enzyme-linked immunosorbent assay. We studied a transduction domain of TcdA (TcdA57-80), which was predicted by machine learning to have cell-penetrating activity and confirmed by synchrotron small-angle X-ray scattering. Intestines of CD1 mice, C57BL6J mice, and mice that express a form of TLR9 that is not activated by CpG DNA were injected with TcdA, TLR9 antagonist, or both. Enterotoxicity was estimated based on loop weight to length ratios. A TLR9 antagonist was tested in mice infected with C difficile. We incubated human colon explants with an antagonist of TLR9 and measured TcdA-induced production of cytokines. RESULTS: The TcdA57-80 protein transduction domain had membrane remodeling activity that allowed TcdA to enter endosomes. TcdA-bound DNA entered human colonocytes. TLR9 was required for production of cytokines by cultured cells and in human colon explants incubated with TcdA. TLR9 was required in TcdA-induced mice intestinal secretions and in the survival of mice infected by C difficile. Even in a protease-rich environment, in which only fragments of TcdA exist, the TcdA57-80 domain organized DNA into a geometrically ordered structure that activated TLR9. CONCLUSIONS: TcdA from C difficile can bind and organize bacterial DNA to activate TLR9. TcdA and TcdA fragments remodel membranes, which allows them to access endosomes and present bacterial DNA to and activate TLR9. Rather than inactivating the ability of DNA to bind TLR9, TcdA appears to chaperone and organize DNA into an inflammatory, spatially periodic structure.
Asunto(s)
Toxinas Bacterianas/metabolismo , Clostridioides difficile/inmunología , Infecciones por Clostridium/inmunología , Colitis/inmunología , Enterotoxinas/metabolismo , Receptor Toll-Like 9/metabolismo , Animales , Antibacterianos/efectos adversos , Clostridioides difficile/genética , Clostridioides difficile/metabolismo , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/microbiología , Colitis/inducido químicamente , Colitis/microbiología , ADN Bacteriano/metabolismo , Modelos Animales de Enfermedad , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Microbioma Gastrointestinal/inmunología , Humanos , Inmunidad Innata , Ratones , Ratones Noqueados , Chaperonas Moleculares/metabolismo , Transducción de Señal/inmunología , Receptor Toll-Like 9/genéticaRESUMEN
BACKGROUND: Clostridium difficile infection is one of the most common causes of diarrhea in healthcare facilities. More studies are needed to identify patients at high risk of C difficile infection in our community. OBJECTIVES: Estimate the prevalence of C difficile infection among adult patients and evaluate the risk factors associated with infection. DESIGN: Retrospective record review. SETTING: Tertiary academic medical center in Jeddah. PATIENTS AND METHODS: Eligible patients were adults (≥18 years old) with confirmed C difficile diagnosis between January 2013 and May 2018. MAIN OUTCOME MEASURES: Prevalence rate and types of risk factors. SAMPLE SIZE: Of 1886 records, 129 patients had positive lab results and met the inclusion criteria. RESULTS: The prevalence of C difficile infection in our center over five years was 6.8%. The mean (SD) age was 56 (18) years, and infection was more prevalent in men (53.5%) than in women (46.5%). The most common risk factors were use of proton-pump inhibitors (PPI) and broad-spectrum antibiotics. The overlapping exposure of both PPIs and broad-spectrum antibiotics was 56.6%. There was no statistically significant difference between the type of PPI (P=.254) or antibiotic (P=.789) and the onset of C difficile infection. CONCLUSION: The overall C difficile infection prevalence in our population was low compared to Western countries. The majority of the patients who developed C difficile infection were using PPIs and/or antibiotics. No differences were observed in the type of antibiotic or PPI and the onset of C difficile infection development. Appropriate prescribing protocols for PPIs and antibiotics in acute settings are needed. LIMITATIONS: Single center and retrospective design. CONFLICT OF INTEREST: None.
Asunto(s)
Antibacterianos/efectos adversos , Infecciones por Clostridium/epidemiología , Infección Hospitalaria/epidemiología , Diarrea/epidemiología , Inhibidores de la Bomba de Protones/efectos adversos , Centros Médicos Académicos , Adulto , Anciano , Infecciones por Clostridium/inducido químicamente , Infección Hospitalaria/inducido químicamente , Diarrea/inducido químicamente , Diarrea/microbiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Retrospectivos , Factores de Riesgo , Arabia Saudita/epidemiologíaRESUMEN
STUDY DESIGN: Retrospective database review. OBJECTIVE: The aim of this study was to determine the incidence of Clostridium difficile infection (CDI) within 90 days following elective spine surgery; examine risk factors associated with its development; and evaluate the impact of CDI on postoperative outcomes. SUMMARY OF BACKGROUND DATA: Although previous studies provided valuable insight into the rate of CDI following spine surgery and associated risk factors, to date no study has evaluated the role preoperative antibiotics use plays in the development of CDI, as well as its impact on 90-day outcomes. METHODS: A retrospective database review of Humana patients ages 20 to 84 years who underwent elective spine surgery between 2008 and 2016 was conducted. Following exclusion criteria, the population was divided into patients who developed CDI within 90 days of surgery and those who did not. All risk factors and outcomes were analyzed using multivariate regression. RESULTS: A total of 63,667 patients met study criteria. Ninety-day incidence of CDI was 0.68%. Notable medical risk factors (Pâ<â0.05) included preoperative fluoroquinolone use (odds ratio [OR] 1.40), advanced age (OR 1.86), chronic kidney disease stage I/II (OR 1.76) and III-V (OR 1.98), decompensated chronic liver disease (OR 3.68), and hypoalbuminemia (OR 3.15). Combined anterior-posterior cervical (OR 2.74) and combined anterior-posterior lumbar (OR 2.43) approaches and procedures spanning more than eight levels (OR 3.99) were associated with the highest surgical risk (Pâ<â0.05) of CDI. CDI was associated with a 12.77-day increase in length of stay (Pâ<â0.05) and increased risk of readmission (OR 6.08, Pâ<â0.05) and mortality (OR 8.94, Pâ<â0.05). CONCLUSION: Following elective spine surgery, CDI increases risk of readmission and mortality. In addition to preoperative fluoroquinolone use, novel risk factors associated with the highest risk of CDI included decompensated chronic liver disease, posterior approaches, and multilevel involvement. Perioperative optimization of modifiable risk factors may help to prevent occurrence of CDI. LEVEL OF EVIDENCE: 3.
Asunto(s)
Antibacterianos/efectos adversos , Infecciones por Clostridium/epidemiología , Procedimientos Quirúrgicos Electivos/efectos adversos , Complicaciones Posoperatorias/epidemiología , Cuidados Preoperatorios/efectos adversos , Enfermedades de la Columna Vertebral/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Clostridioides difficile/aislamiento & purificación , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/diagnóstico , Procedimientos Quirúrgicos Electivos/tendencias , Femenino , Fluoroquinolonas/efectos adversos , Fluoroquinolonas/uso terapéutico , Humanos , Incidencia , Tiempo de Internación/tendencias , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/inducido químicamente , Complicaciones Posoperatorias/diagnóstico , Cuidados Preoperatorios/tendencias , Estudios Retrospectivos , Factores de Riesgo , Enfermedades de la Columna Vertebral/diagnóstico , Enfermedades de la Columna Vertebral/cirugía , Adulto JovenRESUMEN
We describe 9 patients at a medical center in Detroit, Michigan, USA, with severe acute respiratory syndrome coronavirus 2 and Clostridioides difficile. Both infections can manifest as digestive symptoms and merit screening when assessing patients with diarrhea during the coronavirus disease pandemic. These co-infections also highlight the continued importance of antimicrobial stewardship.
Asunto(s)
Betacoronavirus , Clostridioides difficile , Infecciones por Clostridium/epidemiología , Coinfección/epidemiología , Infecciones por Coronavirus/epidemiología , Neumonía Viral/epidemiología , Adulto , Anciano , Antibacterianos/efectos adversos , Programas de Optimización del Uso de los Antimicrobianos , COVID-19 , Infecciones por Clostridium/inducido químicamente , Infecciones por Clostridium/microbiología , Coinfección/microbiología , Infecciones por Coronavirus/microbiología , Femenino , Humanos , Masculino , Michigan/epidemiología , Persona de Mediana Edad , Pandemias , Neumonía Viral/microbiología , Vigilancia de la Población , SARS-CoV-2RESUMEN
BACKGROUND: Clostridioides difficile infection (CDI) has a high recurrent infection rate. Faecal microbiota transplantation (FMT) has been used successfully to treat recurrent CDI, but much remains unknown about the human gut microbiota response to replacement therapies. In this study, antibiotic-mediated dysbiosis of gut microbiota and bacterial growth dynamics were investigated by two quantitative methods: real-time quantitative PCR (qPCR) and direct culture enumeration, in triple-stage chemostat models of the human colon. Three in vitro models were exposed to clindamycin to induce simulated CDI. All models were treated with vancomycin, and two received an FMT. Populations of total bacteria, Bacteroides spp., Lactobacillus spp., Enterococcus spp., Bifidobacterium spp., C. difficile, and Enterobacteriaceae were monitored using both methods. Total clostridia were monitored by selective culture. Using qPCR analysis, we additionally monitored populations of Prevotella spp., Clostridium coccoides group, and Clostridium leptum group. RESULTS: Both methods showed an exacerbation of disruption of the colonic microbiota following vancomycin (and earlier clindamycin) exposure, and a quicker recovery (within 4 days) of the bacterial populations in the models that received the FMT. C. difficile proliferation, consistent with CDI, was also observed by both qPCR and culture. Pearson correlation coefficient showed an association between results varying from 98% for Bacteroides spp., to 62% for Enterobacteriaceae. CONCLUSIONS: Generally, a good correlation was observed between qPCR and bacterial culture. Overall, the molecular assays offer results in real-time, important for treatment efficacy, and allow the monitoring of additional microbiota groups. However, individual quantification of some genera (e.g. clostridia) might not be possible without selective culture.
Asunto(s)
Antibacterianos/efectos adversos , Bacterias/clasificación , Técnicas Bacteriológicas/métodos , Clostridioides difficile/patogenicidad , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal/efectos adversos , Bacterias/genética , Bacterias/crecimiento & desarrollo , Bacterias/aislamiento & purificación , Clindamicina/efectos adversos , Infecciones por Clostridium/inducido químicamente , Colon/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Humanos , Viabilidad Microbiana , Modelos Biológicos , Filogenia , Reacción en Cadena en Tiempo Real de la Polimerasa , Vancomicina/efectos adversosRESUMEN
BACKGROUND: The study's objective was to investigate the incidence and risk factors associated with Clostridioides difficile (previously known as Clostridium) infection (CDI) in children with inflammatory bowel disease (IBD) in the province of Manitoba. METHODS: Our longitudinal population-based cohort was comprised of all children and young adults aged <17 years diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. The Fisher exact test was used to examine the relationship between categorical variables. A Cox regression model was used to estimate the risk of CDI development in IBD patients. RESULTS: Among 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years, and the median age at diagnosis (interquartile range) was 12.96 (9.33-15.81) years. The incidence rates of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (P = 0.46). Compared with children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (adjusted hazard ratio [aHR], 4.38; 95% confidence interval [CI], 1.46-13.10) and anti-tumor necrosis factor (anti-TNF) biologics (aHR, 3.31; 95% CI, 1.11-9.90). The recurrence rate of CDI in our pediatric IBD population was 25%. CONCLUSIONS: Our findings confirm that children with IBD are at high risk of developing CDI, which may predict future escalation of IBD therapy.
Asunto(s)
Clostridioides difficile , Infecciones por Clostridium/epidemiología , Enfermedades Inflamatorias del Intestino/microbiología , Adolescente , Corticoesteroides/efectos adversos , Antibacterianos/efectos adversos , Productos Biológicos/efectos adversos , Niño , Infecciones por Clostridium/inducido químicamente , Femenino , Humanos , Incidencia , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Estudios Longitudinales , Masculino , Manitoba/epidemiología , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: Unnecessary antibiotic use (AU) contributes to increased rates of Clostridioides difficile infection (CDI). The impact of antibiotic restriction on hospital-onset CDI (HO-CDI) has not been assessed in a large group of US acute care hospitals (ACHs). METHODS: We examined cross-sectional and temporal associations between rates of hospital-level AU and HO-CDI using data from 549 ACHs. HO-CDI was defined as a discharge with a secondary International Classification of Diseases, Ninth Revision, Clinical Modification code for CDI (008.45), and treatment with metronidazole or oral vancomycin > 3 days after admission. Analyses were performed using multivariable generalized estimating equation models adjusting for patient and hospital characteristics. RESULTS: During 2006-2012, the unadjusted annual rates of HO-CDI and total AU were 7.3 per 10 000 patient-days (PD) (95% confidence interval [CI], 7.1-7.5) and 811 days of therapy (DOT)/1000 PD (95% CI, 803-820), respectively. In the cross-sectional analysis, for every 50 DOT/1000 PD increase in total AU, there was a 4.4% increase in HO-CDI. For every 10 DOT/1000 PD increase in use of third- and fourth-generation cephalosporins or carbapenems, there was a 2.1% and 2.9% increase in HO-CDI, respectively. In the time-series analysis, the 6 ACHs with a ≥30% decrease in total AU had a 33% decrease in HO-CDI (rate ratio, 0.67 [95% CI, .47-.96]); ACHs with a ≥20% decrease in fluoroquinolone or third- and fourth-generation cephalosporin use had a corresponding decrease in HO-CDI of 8% and 13%, respectively. CONCLUSIONS: At an ecologic level, reductions in total AU, use of fluoroquinolones, and use of third- and fourth-generation cephalosporins were each associated with decreased HO-CDI rates.