Validation of the SHEA/IDSA severity criteria to predict poor outcomes among inpatients and outpatients with Clostridioides difficile infection.

OBJECTIVE: To determine whether the Society for Healthcare Epidemiology of America (SHEA) and the Infectious Diseases Society of America (IDSA) Clostridioides difficile infection (CDI) severity criteria adequately predicts poor outcomes. DESIGN: Retrospective validation study. SETTING AND PARTICIPANTS: Patients with CDI in the Veterans' Affairs Health System from January 1, 2006, to December 31, 2016. METHODS: For the 2010 criteria, patients with leukocytosis or a serum creatinine (SCr) value ≥1.5 times the baseline were classified as severe. For the 2018 criteria, patients with leukocytosis or a SCr value ≥1.5 mg/dL were classified as severe. Poor outcomes were defined as hospital or intensive care admission within 7 days of diagnosis, colectomy within 14 days, or 30-day all-cause mortality; they were modeled as a function of the 2010 and 2018 criteria separately using logistic regression. RESULTS: We analyzed data from 86,112 episodes of CDI. Severity was unclassifiable in a large proportion of episodes diagnosed in subacute care (2010, 58.8%; 2018, 49.2%). Sensitivity ranged from 0.48 for subacute care using 2010 criteria to 0.73 for acute care using 2018 criteria. Areas under the curve were poor and similar (0.60 for subacute care and 0.57 for acute care) for both versions, but negative predictive values were >0.80. CONCLUSIONS: Model performances across care settings and criteria versions were generally poor but had reasonably high negative predictive value. Many patients in the subacute-care setting, an increasing fraction of CDI cases, could not be classified. More work is needed to develop criteria to identify patients at risk of poor outcomes.

Characteristics, risk factors and outcomes of Clostridium difficile infections in Greek Intensive Care Units.

BACKGROUND: Clostridium difficile is one of the major causes of diarrhoea among critically ill patients and its prevalence increases exponentially in relation to the use of antibiotics and medical devices. We sought to investigate the incidence of C. difficile infection in Greek units, and identify potential risk factors related to C. difficile infection. METHODS: A prospective multicenter cohort analysis of critically ill patients (3 ICUs from 1/1/2014 to 31/12/2014). RESULTS: Among 970(100%) patients, 95(9.79%) with diarrhoea, were included. Their demographic, comorbidity and clinical characteristics were recorded on admission to the unit. The known predisposing factors for the infection were recorded and the diagnostic tests to confirm C. difficile were conducted, based on the current guidelines. The incidence of C. difficile infection was 1.3% (n = 13). All-cause mortality in patients with diarrhoea, C. difficile infection and attributable mortality in patients with C. difficile infection was 28%, 38.5% and 30.8% respectively. Sequential Organ Failure Assessment (SOFA) scores on admission were significantly lower and prior C. difficile infection was more common in patients with current C. difficile infection. Regarding other potential risk factors, no difference was found between groups. No factor was independently associated with C. difficile infection. CONCLUSIONS: C. difficile infection is low in Greek intensive care units, but remains a serious problem among the critically-ill. Mortality was similar to reports from other countries. No factor was independently associated with C. difficile infection.

Sleeping with the enemy: Clostridium difficile infection in the intensive care unit.

Over the last years, there was an increase in the number and severity of Clostridium difficile infections (CDI) in all medical settings, including the intensive care unit (ICU). The current prevalence of CDI among ICU patients is estimated at 0.4-4% and has severe impact on morbidity and mortality. An estimated 10-20% of patients are colonized with C. difficile without showing signs of infection and spores can be found throughout ICUs. It is not yet possible to predict whether and when colonization will become infection. Figuratively speaking, our patients are sleeping with the enemy and we do not know when this enemy awakens.Most patients developing CDI in the ICU show a mild to moderate disease course. Nevertheless, difficult-to-treat severe and complicated cases also occur. Treatment failure is particularly frequent in ICU patients due to comorbidities and the necessity of continued antibiotic treatment. This review will give an overview of current diagnostic, therapeutic, and prophylactic challenges and options with a special focus on the ICU patient.First, we focus on diagnosis and prognosis of disease severity. This includes inconsistencies in the definition of disease severity as well as diagnostic problems. Proceeding from there, we discuss that while at first glance the choice of first-line treatment for CDI in the ICU is a simple matter guided by international guidelines, there are a number of specific problems and inconsistencies. We cover treatment in severe CDI, the problem of early recognition of treatment failure, and possible concepts of intensifying treatment. In conclusion, we mention methods for CDI prevention in the ICU.

Concomitant Medical Conditions and Therapies Preclude Accurate Classification of Children With Severe or Severe Complicated Clostridium difficile Infection.

Severe and severe complicated Clostridium difficile infections (SCDI/SCCDI) were retrospectively assessed in a pediatric cohort. Underlying medical conditions and concomitant medical therapy preclude accurate classification of children with SCDI/SCCDI, using current CDI severity definitions. Revised CDI definitions in children should focus on more objective, age-appropriate, and CDI-specific markers of severity.

Application of the ATLAS score for evaluating the severity of Clostridium difficile infection in teaching hospitals in Mexico

Background: For clinicians, a practical bedside tool for severity assessment and prognosis of patients with Clostridium difficileinfection is a highly desirable unmet medical need.Setting: Two general teaching hospitals in northeast Mexico.Population: Adult patients with C. difficileinfection.Methods: Prospective observational study.Results: Patients included had a median of 48 years of age, 54% of male gender and an average of 24.3 days length of hospital stay. Third generation cephalosporins were the antibiotics most commonly used prior to C. difficileinfection diagnosis. Patients diagnosed with C. difficileinfection had a median ATLAS score of 4 and 56.7% of the subjects had a score between 4 and 7 points. Patients with a score of 8 through 10 points had 100% mortality.Conclusion: The ATLAS score is a potentially useful tool for the routine evaluation of patients at the time of C. difficileinfection diagnosis. At 30 days post-diagnosis, patients with a score of ≤3 points had 100% survival while all of those with scores ≥8 died. Patients with scores between 4 and 7 points had a greater probability of colectomy with an overall cure rate of 70.1%.

Application of the ATLAS score for evaluating the severity of Clostridium difficile infection in teaching hospitals in Mexico.

BACKGROUND: For clinicians, a practical bedside tool for severity assessment and prognosis of patients with Clostridium difficile infection is a highly desirable unmet medical need. SETTING: Two general teaching hospitals in northeast Mexico. POPULATION: Adult patients with C. difficile infection. METHODS: Prospective observational study. RESULTS: Patients included had a median of 48 years of age, 54% of male gender and an average of 24.3 days length of hospital stay. Third generation cephalosporins were the antibiotics most commonly used prior to C. difficile infection diagnosis. Patients diagnosed with C. difficile infection had a median ATLAS score of 4 and 56.7% of the subjects had a score between 4 and 7 points. Patients with a score of 8 through 10 points had 100% mortality. CONCLUSION: The ATLAS score is a potentially useful tool for the routine evaluation of patients at the time of C. difficile infection diagnosis. At 30 days post-diagnosis, patients with a score of ≤3 points had 100% survival while all of those with scores ≥8 died. Patients with scores between 4 and 7 points had a greater probability of colectomy with an overall cure rate of 70.1%.

Concordance of the SHEA-IDSA severity classification for Clostridium difficile infection and the ATLAS bedside scoring system in hospitalized adult patients.

PURPOSE: The Society for Healthcare Epidemiology of America and Infectious Diseases Society of America (SHEA-IDSA) guidelines for the treatment of Clostridium difficile infection (CDI) recommend initial treatment of CDI based on disease severity. This severity definition has not been validated or evaluated based on clinical outcomes. The ATLAS scoring system is a validated tool useful in predicting treatment response and mortality in CDI. The main purpose of this study is to evaluate the concordance of the ATLAS scoring system and the SHEA-IDSA staging for CDI severity. METHODS: This was a retrospective study which included hospitalized patients with confirmed CDI. Bivariate analyses compared baseline demographics and clinical information between patients with nonsevere and severe CDI based on the SHEA-IDSA criteria for CDI severity. Kappa scores were calculated to compare the concordance of the two scoring systems in defining CDI severity. Sensitivity and specificity of the ATLAS scoring system to determine CDI severity were calculated using the SHEA-IDSA criteria as the reference standard. RESULTS: Sixty-four patients met inclusion criteria. Of those, 62.5% were classified as mild to moderate CDI, 25% were severe, uncomplicated, and 12.5% were severe, complicated based on SHEA-IDSA criteria. In the bivariate analyses, ATLAS score breakpoints of ≥ 4, ≥ 5, and ≥ 6 revealed moderate agreement with the SHEA-IDSA classification for severity. The sensitivities and specificities for ATLAS scores in predicting CDI severity ranged from 58.3 to 87.5, and 67.5-87.5%, respectively. CONCLUSION: The ATLAS score may be useful in evaluating CDI severity and determining drug therapy selection.

The prediction of complicated Clostridium difficile infections in children.

We validated proposed definitions for severe Clostridium difficile infection (CDI) in adults for prediction of complicated CDI in children. Complicated CDI occurred in 9 of 202 cases. Definitions for severe CDI in adults showed poor measures for discrimination of complicated CDI in children, which calls into question the usefulness of such definitions in pediatric cohorts.

Multiplex PCR targeting slpA: a rapid screening method to predict common Clostridium difficile ribotypes among fluoroquinolone resistant clinical strains.

AIMS: Based on the relationship between Clostridium difficile surface layer protein A (slpA) sequence types (STs) and PCR-ribotypes (RTs), a multiplex polymerase chain reaction (mPCR) assay was developed to rapidly confirm C. difficile toxigenicity and, simultaneously, to identify any of five slpA STs, gr, hr, fr, gc8 and 078, that usually correspond with globally distributed RTs, 001, 014, 017, 027 and 078, respectively. METHODS: The mPCR, containing five slpA type-specific primers, was developed using 46 well-characterised C. difficile reference strains, representing 11 slpA STs, and validated by testing 90C. difficile clinical isolates. RESULTS: The slpA mPCR correctly identified the five slpA STs without cross-reactions. A much higher proportion of moxifloxacin resistant (32/39; 82%) than susceptible (12/51; 24%) clinical isolates were slpA typeable (χ=30.3, p<0.0001), even when RT027 isolates were excluded [10/17 (59%) versus 12/51 (24%); χ=7.3, p=0.0071<0.01]. slpA mPCR correctly predicted the RTs of all 39 isolates that belonged to the five targeted RTs. CONCLUSION: slpA mPCR is simple, rapid and inexpensive. It can provisionally identify five globally significant, highly transmissible RTs, particularly among moxifloxacin resistant C. difficile isolates, and could be easily modified to include a broader range of slpA sequence types, based on local requirements.

The impact of ICD-9-CM code rank order on the estimated prevalence of Clostridium difficile infections.

BACKGROUND: US estimates of the Clostridium difficile infection (CDI) burden have utilized International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes. Whether ICD-9-CM code rank order affects CDI prevalence estimates is important because the National Hospital Discharge Survey (NHDS) and the Nationwide Inpatient Sample (NIS) have varying limits on the number of ICD-9-CM codes collected. METHODS: ICD-9-CM codes for CDI (008.45), C. difficile toxin assay results, and dates of admission and discharge were collected from electronic hospital databases for adult patients admitted to 4 hospitals in the United States from July 2000 through June 2006. CDI prevalence per 1000 discharges was calculated and compared for NHDS and NIS limits and toxin assay results from the same hospitals. CDI prevalence estimates were compared using the χ(2) test, and the test of equality was used to compare slopes. RESULTS: CDI prevalence measured by NIS criteria was significantly higher than that measured using NHDS criteria (10.7 cases per 1000 discharges versus 9.4 cases per 1000 discharges; P<.001) in the 4 hospitals. CDI prevalence measured by toxin assay results was 9.4 cases per 1000 discharges (P=.57 versus NHDS). However, the CDI prevalence increased more rapidly over time when measured according to the NHDS criteria than when measured according to toxin assay results (ß=1.09 versus 0.84; P=.008). CONCLUSIONS: Compared with the NHDS definition, the NIS definition captured 12% more CDI cases and reported significantly higher CDI rates. Rates calculated using toxin assay results were not different from rates calculated using NHDS criteria, but CDI prevalence appeared to increase more rapidly when measured by NHDS criteria than when measured by toxin assay results.

Comparison of clinical severity score indices for Clostridium difficile infection.

OBJECTIVE: To compare 8 severity score indices for Clostridium difficile infection (CDI). DESIGN: Prospective observational study. METHODS: This study was conducted from July through October 2006. All hospitalized patients in 3 university-affiliated hospitals with a positive fecal Clostridium difficile toxin assay result were evaluated. Infection was considered severe if patients had at least 1 of the following clinical events during their hospitalization: (1) death attributed to CDI within 30 days after diagnosis, (2) colectomy necessitated by CDI, or (3) intensive care unit admission for management of complications attributed to CDI. Severity was assessed on the basis of 8 severity score indices, using published criteria for severe CDI as the benchmark. The 8 severity score indices studied were Beth Israel, University of Pittsburgh Medical Center version 1, University of Pittsburgh Medical Center version 2, Hines VA, modified University of Illinois, University of Calgary version 1, University of Calgary version 2, and University of Temple. RESULTS: Of 184 patients with CDI evaluated, 19 had severe cases and 165 had nonsevere cases, as assessed on the basis of the defined severe CDI criteria. Sensitivities of the 8 severity score indices studied ranged from 63.2% to 84.2%, and specificities ranged from 59.4% to 93.9%. The Hines VA index had the highest kappa score (0.69 [95% confidence interval, 0.54-0.83]), followed by the University of Pittsburgh Medical Center version 1 index. Independent risk factors for severe CDI determined by multivariate analysis were abdominal distention (P = .007), fever (temperature, 38.0°C or above; P = .042), white blood cell count of at least 20,000 cells/mm(3) (P = .035), and hypoalbuminemia (serum albumin level less than 3 mg/dL; P = .029). CONCLUSION: The Hines VA CDI severity score index appeared to display the strongest correlation for predicting more severe forms of CDI.

Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children.

A hypervirulent strain of Clostridium difficile-labeled North American Pulsed Field type 1 causes severe disease in adults. To determine the prevalence of NAP1 C. difficile in children, organisms from consecutive C. difficile toxin-positive stool samples at 2 children's hospitals microbiology laboratories were characterized. We found that 19.4% of these samples were NAP1.

Prevalence of toxin A-nonproducing/toxin-B-producing Clostridium difficile in the Tsukuba-Tsuchiura district, Japan.

In Japan, many clinical laboratories may not have recognized toxin A-nonproducing/toxin B-producing (A-/B+) Clostridium difficile, because rapid diagnostic kits detecting toxin B of C. difficile have not been available in the laboratories. Therefore, we examined the prevalence of A-/B+ strains in the Tsukuba-Tsuchiura district, Japan. Fecal specimens submitted for C. difficile toxin tests in four tertiary hospitals in the district were collected for 6 months. Several C. difficile A-/B+ strains, isolated in two nosocomial outbreaks that had occurred in geographically distant areas in Japan, were also simultaneously analyzed as controls. C. difficile was isolated from 159 of 332 specimens collected. Ten (6.3%) of the 159 C. difficile strains were A-/B+ strains. Nine A-/B+ strains, isolated in one hospital, had an identical genomic pattern by polymerase chain reaction (PCR) ribotyping and macrorestriction analysis with pulsed-field gel electrophoresis (PFGE). The A-/B+ strain isolated in another hospital and some of those in the geographically distant hospitals were indistinguishable from the nine strains by PCR ribotyping but were distinguishable with PFGE analysis. We concluded that A-/B+ strains are not epidemic in this district and that PFGE analysis may be preferable to PCR ribotyping for the genotyping of C. difficile A-/B+ strains. The reason why most of the A-/B+ strains were detected in the one hospital was unclear.

Clostridial toxins - potent poisons, potent medicines

Clostridium is an anaerobic bacterial genus. The clostridia produce more protein toxins than any other bacterial genus and are a rich reservoir of toxins for research and medicinal uses. Clostridia are widely spread in the environment: soil, dust and water, presenting more than 120 described species, although few can cause diseases. Diseases can grossly be divided into neurotropic disorders (nervous system is primarily affected), enterotoxemias (affecting intestinal tract and parenchymatous organs), and gas gangrene (myonecrosis with toxemia). Undoubtedly the most widely recognized infection due to anaerobes was clostridial myonecrosis, but recently interest has arisen for the role of clostridia in intestinal diseases. This report describes the most important species, the diseases caused by them, and their occurrence in Brazil, focusing on cattle raising

Gangrenous and crepitant cellulitis.

A dangerous and little-discussed group of soft tissue (skin, subcutaneous tissue, fascia, and skeletal muscle) infections are characterized by the presence of extensive gangrene and/or discernible tissue gas. The identifying characteristics of these infections, as well as diagnostic measures and therapy, are reviewed.