High Horn's index score predicts poor outcomes in patients with Clostridium difficile infection

Several variables have been proposed to predict the prognosis of patients with Clostridium difficile infection (CDI), but a clinically useful tool to stratify resource utilization has not been determined. Horn's index, a severity score based on underlying clinical illness, reliably predicts patients at high risk of CDI. The purpose of this study was to assess the use of Horn's index to stratify patients with CDI at high risk of poor clinical and economic outcomes. Hospitalized patients diagnosed with CDI were followed prospectively for three months. Horn's index scores were calculated for each patient on the day of the positive toxin test for C. difficile, and used to stratify differences in outcome variables (length of hospital stay, mortality and hospital costs). Eighty-five CDI patients (50% male, 64% Caucasian) were recruited. Discharge mortality was 0% for patients with Horn's index scores of 1 or 2, 5% for those with a score of 3, and 50% for those with a score of 4 (P < 0.001). Three-month mortality was 0%, 5%, 17% and 60% for patients with Horn's index scores of 1, 2, 3 and 4, respectively (P = 0.0004). Median three-month hospital costs were $8,585, $12,670, $29,077 and $68,708 for patients with Horn's index scores of 1, 2, 3 and 4, respectively (P < 0.001). Patients with Horn's index scores of 3 or 4 had a significantly longer hospital stay [mean 33.4 (standard deviation, SD 33.3) days] than patients with scores of 1 or 2 [mean 15.1 (SD 16.2) days, P = 0.001]. This study found Horn's index to be a simple and useful method for identifying CDI patients at high risk of poor clinical and economic outcomes.     

CSI: a severity index for Clostridium difficile infection at the time of admission

Clostridium difficile is a common cause of nosocomial diarrhoea in the USA. To develop a score model that would help to identify severe versus mild or moderate C. difficile infection (CDI) upon admission we performed a retrospective cohort study. Between January 2004 and December 2007, 255 patients met inclusion criteria for this study. Severe CDI was defined as cases that required colectomy, intensive care unit management, ended in death, or hospitalisation of >10 days. Data recorded included past medical history, physical examination on admission, laboratory data and imaging/colonoscopy data. To create the CDI severity index (CSI) score, we included four risk factors for severe CDI that were identified by univariate analysis: history of malignancy, white blood cell count at admission >20,000/dL, blood albumin <3.0mg/dL, and creatinine at admission >1.5-fold the baseline value. One point was assigned to each of the risk factors. As indicated by a c-statistic of 0.78, the CSI score predicted severe CDI much better than chance (c-statistics of 0.50). The risk of developing severe CDI increased by a factor of 2.9 (95% CI: 1.82-4.59) for each 1-point increase in the CSI score. A CSI score with a cut-off value of 2 had a sensitivity and specificity of 82% and 65%, respectively. The CSI score may quantify the risk of severe CDI at the time of admission, and help in early identification of patients who may benefit from more aggressive treatment.     

Mortality of patients with antibiotic-associated diarrhoea: the impact of Clostridium difficile

Previous studies have shown conflicting results concerning mortality related to Clostridium difficile infection. The objective of this study was to determine the impact of C. difficile infection on short- and long-term mortality in hospitalised patients with antibiotic-associated diarrhoea. We therefore undertook a prospective case-control study of 217 hospitalised patients who received antibiotics, developed diarrhoea and underwent stool enzyme immunoassay for C. difficile TOX A/B. The Kaplan-Meier and the log-rank test were used to determine univariate survival analysis and a Cox regression model for multivariate analysis of 28 day and long-term mortality. Fifty-two (24%) of the 217 patients who met the study criteria were positive for C. difficile TOX A/B. The crude 28 day and long-term mortality rates of the entire cohort were 12.4% and 56%, respectively. On Cox regression analysis, hypoalbuminaemia, impaired functional capacity and elevated serum urea levels were found to be the only independent and statistically significant variables associated with long-term mortality. C. difficile toxin positivity per se was not associated with increased short- or long-term mortality rates. In conclusion, hypoalbuminaemia, renal failure, and impaired function capacity predict mortality due to antibiotic-associated diarrhoea, but C. difficile involvement by itself does not further increase the risk of death in these patients.     

Automated system to identify Clostridium difficile infection among hospitalised patients

The purpose of this study was to assess whether data on stool frequency collected electronically could identify patients at high risk for Clostridium difficile infection (CDI). All patients with reports of diarrhoea were assessed prospectively for number of stools per day and number of diarrhoea days. C. difficile testing was requested independently from study investigators. Number of days with diarrhoea and maximum number of unformed stools was assessed as a CDI predictor. A total of 605 patients were identified with active diarrhoea of whom 64 (10.6%) were diagnosed with CDI. In univariate analysis, the maximum number of stools and number of diarrhoea days was associated with increased risk of CDI. Compared to patients with three diarrhoea stools per day (CDI incidence: 6.3%), CDI increased to 13.4% in patients with four or more diarrhoea stools per day [odds ratio (OR): 2.3; 95% confidence interval (CI): 1.3–4.2; P = 0.0054]. Compared to patients with one day of diarrhoea (CDI incidence: 6.3%), CDI increased to 17.4% in patients with two diarrhoea days (OR: 3.1; 95% CI: 1.7–5.6) and to 27.1% in patients with three or more diarrhoea days (OR: 5.5; 95% CI: 2.6–11.7). These results were validated using logistic regression with number of days with diarrhoea identified as the most important predictor. Using an electronic data capture technique, number of days of diarrhoea and maximum number of diarrhoea stools in a 24 h time period were able to identify a patient population at high risk for CDI.     

Co-morbidities as predictors of mortality in Clostridium difficile infection and derivation of the ARC predictive score

Clostridium difficile associated diarrhoea (CDAD) has increased significantly in the last 15 years, but predictors of outcome are inadequately understood. This was a cohort study of 2761 patients in North East England between 2002 and 2009, with the end-point of mortality at 30 days. The role of age, gender and co-morbidities was examined by binary logistic regression. Rounded odds ratios were used to develop a predictive score. A predictive score based on age, renal disease and cancer (ARC score) differentiated groups with differing risk of 30-day mortality (risk for score of 0-3 was 9-21%, score of 4-7 was 31-48% and score of 8 was 66%). Co-morbidities were shown to be important predictors of outcome in CDAD, and can be combined with age in the ARC score to assess the likelihood of survival. This requires further validation in other populations, but has important implications for clinical and research practice.     

Aerial dissemination of Clostridium difficile on a pig farm and its environment

Clostridium difficile is increasingly recognized as an important enteropathogen in both humans and animals. The finding of C. difficile in air samples in hospitals suggests a role for aerial dissemination in the transmission of human C. difficile infection. The present study was designed to investigate the occurrence of airborne C. difficile in, and nearby a pig farm with a high prevalence of C. difficile. Airborne colony counts in the farrowing pens peaked on the moments shortly after or during personnel activity in the pens (P=0.043 (farrowing pens 1, 2), P=0.034 (farrowing pen 2)). A decrease in airborne C. difficile colony counts was observed parallel to aging of the piglets. Airborne C. difficile was detected up to 20 m distant from the farm.This study showed widespread aerial dissemination of C. difficile on a pig farm that was positively associated with personnel activity.     

High prevalence of toxinogenic Clostridium difficile in Nigerian adult HIV patients

Clostridium difficile is the most commonly identified bacterial cause of nosocomial and HIV-related diarrhea. In many developing countries, antibiotic access is unregulated. Nigeria has the third highest HIV burden worldwide. Due to perceptions of low prevalence and resource incapacity, patients with diarrhea are not tested for toxinogenic C. difficile infection (CDI). In this pilot study which included 97 HIV-positive patients at two hospitals in Nigeria, the estimated prevalence of CDI was 43% and 14% for in-patients and out-patients respectively. HIV-positive out-patients were more likely to have toxinogenic CDI than non-HIV out-patients (P = 0.007, Fisher's exact test).     

Clostridium difficile: development of a novel candidate vaccine

Clostridium difficile has become the most frequent hospital-acquired infection in North America and the EU. C. difficile infection (CDI) is present worldwide and disease awareness is increasing. In the US, EU, and Canada, in addition to hospital diagnosed disease, CDI has also been reported with increasing frequency in the community. Hypervirulent strains have increased the morbidity and mortality associated with CDI. Current treatment options are suboptimal. Of all patients treated for CDI, 20% relapse and 65% of those experiencing a second relapse become chronic cases. An association between increased serum levels of IgG antibody against toxin A and asymptomatic carriage of C. difficile provides a rationale for vaccine development. Sanofi Pasteur's C. difficile candidate vaccine is being developed for the prevention of primary disease. The target population is adults at risk of CDI, those with planned hospitalization, long-term care/nursing home residents, and adults with co-morbidities requiring frequent/prolonged antibiotic use.     

Clostridium difficile infection in patients discharged from US short-stay hospitals, 1996-2003

US hospital discharges for which Clostridium difficile-associated disease (CDAD) was listed as any diagnosis doubled from 82,000 (95% confidence interval [CI] 71,000-94,000) or 31/100,000 population in 1996 to 178,000 (95% CI 151,000-205,000) or 61/100,000 in 2003; this increase was significant between 2000 and 2003 (slope of linear trend 9.48; 95% CI 6.16-12.80, p = 0.01). The overall rate during this period was severalfold higher in persons >65 years of age (228/100,000) than in the age group with the next highest rate, 45-64 years (40/100,000; p < or = 0.001). CDAD appears to be increasing rapidly in the United States and is disproportionately affecting older persons. Clinicians should be aware of the increasing risk for CDAD and make efforts to control transmission of C. difficile and prevent disease.     

Low prevalence of nosocomial Clostridium difficile transmission, as determined by comparison of arbitrarily primed PCR and epidemiological data

An increased prevalence of patients with C. difficile-associated diarrhoea in a hospital setting suggested the possible existence of an endemic occurrence. A study was therefore designed to determine clonal relatedness among 173 isolates of C. difficile, collected consecutively during 1995 from 147 patients (89 inpatients and 58 outpatients) and to estimate the probability of nosocomial transmission. Arbitrarily primed PCR (AP-PCR) with three different primers, AP1, AP2 and CLD1, was used for fingerprinting and identified 21, 92 and 70 types, respectively. Overall DNA analysis of the combined AP-PCR data yielded 140 types, of which 130 were unique, whereas 10 types occurred repeatedly in 36 isolates from 33 patients; seven isolates were non-typeable by one of the primers. Epidemiological data confirmed that in eight of the 33 patients there was a high probability of nosocomial transmission. Despite a high prevalence of C. difficile among hospitalized patients, a low frequency of nosocomial transmission was suggested by high resolution molecular typing of bacterial isolates in conjunction with traditional epidemiological methods.     

Activity of a dry mist hydrogen peroxide system against environmental Clostridium difficile contamination in elderly care wards

Clostridium difficile causes serious healthcare-associated infections. Infection control is difficult, due in part to environmental contamination with C. difficile spores. These spores are relatively resistant to cleaning and disinfection. The activity of a dry mist hydrogen peroxide decontamination system (Sterinis((R))) against environmental C. difficile contamination was assessed in three elderly care wards. Initial sampling for C. difficile was performed in 16 rooms across a variety of wards and specialties, using Brazier's CCEY (cycloserine-cefoxitin-egg yolk) agar. Ten rooms for elderly patients (eight isolation and two sluice rooms) were then resampled following dry mist hydrogen peroxide decontamination. Representative isolates of C. difficile were typed by polymerase chain reaction ribotyping. C. difficile was recovered from 3%, 11% and 26% of samples from low, medium and high risk rooms, respectively. In 10 high risk elderly care rooms, 24% (48/203) of samples were positive for C. difficile, with a mean of 6.8 colony-forming units (cfu) per 10 samples prior to hydrogen peroxide decontamination. Ribotyping identified the presence of the three main UK epidemic strains (ribotypes 001, 027 and 106) and four rooms contained mixed strains. After a single cycle of hydrogen peroxide decontamination, only 3% (7/203) of samples were positive (P<0.001), with a mean of 0.4 cfu per 10 samples ( approximately 94% reduction). The Sterinis((R)) hydrogen peroxide system significantly reduced the extent of environmental contamination with C. difficile in these elderly care rooms. This relatively quick and user-friendly technology might be a more reliable method of terminally disinfecting isolation rooms, following detergent cleaning, compared to the manual application of other disinfectants.     

Clostridium difficile acquisition rate and its role in nosocomial diarrhoea at a university hospital in Turkey

Infection with Clostridium difficile can present with various clinical pictures ranging from an asymptomatic carrier state to pseudomembranous colitis and plays an important part in the etiology of nosocomial diarrhoea. To identify risk factors for C. difficile colonization and diarrhoea in hospitalized subjects, patients admitted to a general medicine ward at Marmara University hospital during a one year period were entered into the study. Of the 202 patients, nosocomial diarrhoea developed in 45 (22.3%). Fourteen patients (6.9%) were colonized with C. difficile during their hospitalization period. Ten of the colonized patients (71.4%) developed diarrhoea and were found to be positive by toxin assay. Pseudomembranous colitis was confirmed endoscopically in 3 of the patients with diarrhoea. Administration of beta lactam agents such as ampicillin and cephalosporins; gastrointestinal manipulations and admission to the intensive care unit were found as major risk factors for C. difficile colonization.     

Single-dose cefuroxime with gentamicin reduces Clostridium difficile-associated disease in hip-fracture patients

Antibiotic-associated Clostridium difficile diarrhoea may complicate recovery from surgery for proximal femoral fracture. We undertook a four-year case-control study to evaluate a change in antibiotic prophylaxis in our department. During the period January 2003 to January 2005, patients received three doses of prophylactic cefuroxime (1.5g). We then introduced a new regimen, comprising of one single dose of cefuroxime (1.5g) with gentamicin (240mg) at induction. Prior to the change in prophylaxis, 912 patients underwent surgery for neck of femur fracture, and from March 2005 to March 2007, 899 patients had surgery under the new regimen. Thirty-eight patients developed C. difficile infection (4.2%) in the initial group, compared with 14 patients (1.6%) in the group with the new regimen (P=0.009). The incidence of C. difficile infection increased throughout the rest of the hospital over the same time period. Patients with C. difficile infection had a statistically significant increase in antibiotic exposure, inpatient stay, morbidity and inpatient mortality. The main challenges regarding prophylactic antibiotic selection are infection due to meticillin-resistant Staphylococcus aureus (MRSA) and C. difficile-associated diarrhoea. We advocate the use of the new regimen as an alternative to multiple-dose cephalosporin antibiotics for the prevention of C. difficile infection in this group of high-risk patients.     

Prevalence of Clostridium difficile in the environment in a rural community in Zimbabwe

Clostridium difficile has been shown to be a nosocomial pathogen associated with diarrhoea and pseudomembranous colitis in hospitalised patients, but very little is known about its prevalence outside the hospital environment. The aim of this study was to determine the prevalence of C. difficile in faeces of domestic animals, soil and drinking water in a rural community. Water, animal faeces and soil were collected from homesteads in a rural community and the samples were cultured for C. difficile.Clostridium difficile isolates that produced toxins A or B were tested for their susceptibility to antimicrobial drugs. Clostridium difficile was isolated from 37.0% of 146 soil samples, 17.4% of 115 chicken faeces samples, 6.0% of 234 water samples and 4.3% of 161 faecal samples of other animals. Some of the C. difficile isolates from chickens (55.0%), soil (66.7%) and water (14.3%) were toxigenic. All toxigenic isolates were susceptible to metronidazole, vancomycin, doxycycline, chloramphenicol and tetracycline and all were resistant to cefotaxime, gentamicin, ciprofloxacin, norfloxacin and nalidixic acid. The results of the present study suggest that chickens kept by villagers are an important reservoir of C. difficile, which may act as a source of human infection.     

Laboratory diagnosis of Clostridium difficile-associated disease in the Republic of Ireland: a survey of Irish microbiology laboratories

The Health Protection Surveillance Centre (HPSC) established a group to produce national guidelines for Clostridium difficile in Ireland in 2006. A laboratory questionnaire was distributed to determine current C. difficile diagnostic practices. Twenty-nine out of 44 laboratories providing C. difficile diagnostic services to 34 hospitals responded. Twenty-five out of 29 (86%) laboratories processed specimens for C. difficile and four (13.8%) forwarded specimens to another laboratory. Sixteen laboratories (64%) processed specimens for other healthcare facilities. None routinely examined stool for C. difficile, seven (28%) examined specimens only when requested to do so and 18 (72%) used specific selection criteria, including testing all liquid stools (39%), all nosocomial diarrhoea (44%), specific clinical criteria (28%) and history of antibiotic therapy (22%). All tested stool directly for C. difficile toxin with a variety of enzyme immunoassays, with 24 (96%) detecting both toxin A and B and one detecting toxin A only. Three (12%) laboratories used cytotoxicity assays; none used polymerase chain reaction and six (24%) laboratories performed C. difficile culture but only under specific circumstances. Seven (28%) laboratories had isolates typed during outbreaks, but none had the facilities to do so on-site. The HPSC group will produce national recommendations for laboratory diagnosis, surveillance and management of C. difficile infection. Since there are marked differences in diagnostic practices throughout the country and no national reference laboratory, the implementation of these recommendations will have cost implications that will need to be addressed.     

Phase I dose finding studies of an adjuvanted Clostridium difficile toxoid vaccine

Fifty healthy adult (18-55 years) and 48 elderly (≥ 65 years) volunteers were randomized to receive a candidate Clostridium difficile toxoid vaccine (2 μg, 10 μg, or 50 μg) or placebo on Days 0, 28, and 56. No volunteer receiving placebo seroconverted. For toxin A, seroconversion by Day 56 (post-dose 2) was observed in 100% of volunteers aged 18-55 years in all dose groups and in 50%, 89%, and 100% of elderly participants in the 2 μg, 10 μg, and 50 μg dose groups, respectively. For both age groups, seroconversion for toxin B was lower than toxin A. There were no safety concerns.     

Risk factors and clinical significance of ertapenem-resistant Klebsiella pneumoniae in hospitalised patients

Ertapenem-resistant Klebsiella pneumoniae (ER-Kp) is an emerging healthcare-associated pathogen. In order to identify risk factors associated with ER-Kp acquisition, the records of 100 patients from whom K. pneumoniae had been isolated between July 2008 and December 2009 were reviewed. These comprised 38 with ER-Kp (28 infected, 10 colonised) and 62 with ertapenem-susceptible K. pneumoniae (ES-Kp) (43 infected, 19 colonised). Multilocus sequence typing (MSLT) and porin gene investigation performed on 25 ER-Kp strains showed that 24 belonged to the ST37 lineage, expressing a novel OmpK36 variant and not expressing OmpK35. Breakthrough bacteraemia occurred in 13 (52%) of 25 bloodstream infections (BSIs). Among nine ER-Kp BSIs, five were complicated by breakthrough bacteraemia, of which four developed during carbapenem therapy. Among 16 ES-Kp BSIs, breakthrough bacteraemia developed in eight patients (50%), but only one occurred (12%) during carbapenem therapy. Logistic regression analysis showed that carbapenems (odds ratio: 12.9; 95% confidence interval: 3.09-53.7; P < 0.001), second generation cephalosporins (11.8; 1.87-74.4; P < 0.01), endoscopy (5.59; 1.32-23.6; P < 0.02), acute renal failure (5.32; 1.13-25.1; P=0.034) and third generation cephalosporins (4.15; 1.09-15.8; P < 0.01) were independent risk factors for acquisition of ER-Kp. Our findings confirm that prior use of certain antimicrobials, specifically carbapenems and cephalosporins, are primary independent risk factors for colonisation or infection with ER-Kp.