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.     

Nosocomial diarrhea and Clostridium Difficile associated diarrhea in a Turkish University Hospital

Background

Clostridium difficile (C. difficile) is a well-established cause of nosocomial diarrhea. The aim of our study was to define the incidence of nosocomial diarrhea in our hospital and to determine the role of C. difficile. Additionally, the risk factors for nosocomial diarrhea and Clostridium difficile associated diarrhea (CDAD) were investigated.

Methods

We included all patients, 18 years of age or more, who were admitted to the Uludag Teaching Hospital between October 1, 2004 and February 1, 2005, and developed diarrhea at least three days after hospital admission. A case-control study was performed.

Results

The total incidence of nosocomial diarrhea was 0.6 per 1,000 hospitalization-days and 5 per 1,000 patients’ admissions. Previous use of chemotherapy was found to be an important predisposing factor for nosocomial diarrhea. The incidence of CDAD was 0.26 per 1,000 hospitalization-days and 2.1 per 1,000 admissions, comparable with incidence rates in Europe.CDAD was diagnosed in 43% of patients with nosocomial diarrhea. No severe cases of CDAD were diagnosed. A correlation was found between CDAD and antibiotic use before admission and during admission in univariate analysis. PCR ribotyping revealed four strains of PCR ribotype 002 and 1 strain of ribotype 012 out of 5 C. difficile strains available for extensive identification.

Conclusion

The incidence rates of nosocomial diarrhea and CDAD are not different than the usual incidence rates in Europe. C. difficile was the causative agent in 43% of patients with nosocomial diarrhea.     

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.     

Probiotics reduce symptoms of antibiotic use in a hospital setting: A randomized dose response study

Probiotics are known to reduce antibiotic associated diarrhea (AAD) and Clostridium difficile associated diarrhea (CDAD) risk in a strain-specific manner. The aim of this study was to determine the dose-response effect of a four strain probiotic combination (HOWARU^® Restore) on the incidence of AAD and CDAD and severity of gastrointestinal symptoms in adult in-patients requiring antibiotic therapy. Patients (n = 503) were randomized among three study groups: HOWARU^® Restore probiotic 1.70 × 10¹⁰ CFU (high-dose, n = 168), HOWARU^® Restore probiotic 4.17 × 10⁹ CFU (low-dose, n = 168), or placebo (n = 167). Subjects were stratified by gender, age, and duration of antibiotic treatment. Study products were administered daily up to 7 days after the final antibiotic dose. The primary endpoint of the study was the incidence of AAD. Secondary endpoints included incidence of CDAD, diarrhea duration, stools per day, bloody stools, fever, abdominal cramping, and bloating. A significant dose-response effect on AAD was observed with incidences of 12.5, 19.6, and 24.6% with high-dose, low-dose, and placebo, respectively (p = 0.02). CDAD was the same in both probiotic groups (1.8%) but different from the placebo group (4.8%; p = 0.04). Incidences of fever, abdominal pain, and bloating were lower with increasing probiotic dose. The number of daily liquid stools and average duration of diarrhea decreased with higher probiotic dosage. The tested four strain probiotic combination appears to lower the risk of AAD, CDAD, and gastrointestinal symptoms in a dose-dependent manner in adult in-patients.     

Antimicrobial drugs and community-acquired Clostridium difficile-associated disease, UK

In a population-based case-control study of community acquired Clostridium difficile-associated disease (CDAD), we matched 1,233 cases to 12,330 controls. CDAD risk increased 3-fold with use of any antimicrobial agent and 6-fold with use of fluoroquinolones. Prior use of antimicrobial agents did not affect risk for CDAD after 6 months.     

Risk of Clostridium difficile-associated disease among patients receiving proton-pump inhibitors in a Quebec medical intensive care unit.

Our study was conducted to determine whether use of gastric acid-suppressive agents increased the risk of Clostridium difficile-associated disease (CDAD) in a medical intensive care unit of one of the first hospitals to be threatened by the current CDAD epidemic in Quebec, Canada. Our findings suggest that efforts to determine risk factors for CDAD should focus on other areas, such as older age and antibiotic use.     

Case-control study of antibiotic use and subsequent Clostridium difficile-associated diarrhea in hospitalized patients.

OBJECTIVE: To determine which antibiotics increase or decrease the risk of Clostridium difficile-associated diarrhea (CDAD). DESIGN: Retrospective case-control study. SETTING: Nonprofit, integrated healthcare delivery system in Northern California. PATIENTS: Study participants included patients with cases of hospital-acquired CDAD that occurred during the period from 1999 through 2005 (n=1,142) and control patients (n= 3,351) matched for facility, calendar quarter during which hospitalization occurred, diagnosis related group for the index hospitalization, and length of hospital stay. All case and control patients had received antibiotics in the 60 days before the index date. For each antibiotic, the risk of CDAD was examined in relation to whether the patient received the antibiotic, after adjustment for use of other antibiotics, demographic characteristics, selected health conditions, and use of healthcare services. RESULTS: The following antibiotics were associated with a significantly increased risk of acquiring CDAD: imipenem-cilastin (odds ratio [OR], 2.77), clindamycin (OR, 2.31), cefuroxime (OR, 2.16), moxifloxacin (OR, 1.88), ceftazidime (OR, 1.82), cefpodoxime (OR, 1.58), ceftizoxime (OR, 1.57), and ceftriaxone (OR, 1.49). Metronidazole and doxycycline were associated with a significantly reduced risk of CDAD (OR for metronidazole, 0.67; OR for doxycycline, 0.41). Other factors associated with an increased risk of CDAD were older age, longer hospital stays, use of proton pump inhibitors, prior gastrointestinal disease, and prior infection (not including C. difficile infection.) CONCLUSIONS: Some antibiotics appear to increase the risk of acquiring CDAD, notably clindamycin, third-generation cephalosporins, and carbapenems, whereas metronidazole and doxycycline appear to be protective, compared with other antibiotics.     

Clostridium difficile in the intensive care unit: epidemiology, costs, and colonization pressure.

OBJECTIVE: To evaluate the epidemiology, outcomes, and importance of Clostridium difficile colonization pressure (CCP) as a risk factor for C. difficile-associated disease (CDAD) acquisition in intensive care unit (ICU) patients. DESIGN: Secondary analysis of data from a 30-month retrospective cohort study. SETTING: A 19-bed medical ICU in a midwestern tertiary care referral center. PATIENTS: Consecutive sample of adult patients with a length of stay of 24 hours or more between July 1, 1997, and December 31, 1999. RESULTS: Seventy-six (4%) of 1,872 patients were identified with CDAD; 40 (53%) acquired CDAD in the ICU, for an incidence of 3.2 cases per 1,000 patient-days. Antimicrobial therapy, enteral feeding, mechanical ventilation, vancomycin-resistant enterococci (VRE) colonization or infection, and CCP (5.5 vs 2.0 CDAD case-days of exposure for patients with acquired CDAD vs no CDAD; P=.001) were associated with CDAD acquisition in the univariate analysis. Only VRE colonization or infection (45% of patients with acquired CDAD vs 16% of patients without CDAD; adjusted odds ratio, 2.76 [95% confidence interval, 1.36-5.59]) and a CCP of more than 30 case-days of exposure (20% with acquired CDAD vs 2% with no CDAD; adjusted odds ratio, 3.77 [95% confidence interval, 1.14-12.49]) remained statistically significant in the multivariable analysis. Lengths of stay (6.1 vs 3.0 days; P<.001 by univariate analysis) and ICU costs ($11,353 vs $6,028; P<.001 by univariate analysis) were higher for patients with any CDAD than for patients with no CDAD. CONCLUSIONS: In this nonoutbreak setting, the CCP was an independent risk factor for acquisition of CDAD in the ICU at the upper range of exposure duration. Having CDAD in the ICU was a marker of excess healthcare use.     

Risk factors for nosocomial Clostridium difficile diarrhoea in an infectious and tropical diseases department

FOREWORD: Clostridium difficile associated diarrhea (CDAD) accounts for 25% of all cases of diarrhea occurring in hospital. Infectious diseases departments are considered as presenting with an important risk of CDAD because of the large quantity of antibiotics used. OBJECTIVES AND METHOD: The authors made a prospective study in the first 6 months of 2001, in order to identify the risk factors of CDAD in their department. One hundred and fifty-two patients hospitalized for at least 6 days were included in this study. The studied factors were: age, mean number of days of hospitalization (MDH), antibiotic therapy, WHO scale of reduced mobility of patients, recent hospitalization (less than 3 months before). RESULTS: MDH was 36 (IC95%: 23-48). Beta-lactam antibiotics were found as significant risk factors, as reported in the literature. However, age and a recent hospitalization were not related to the CDAD as described in the literature. A reduced mobility of patients was identified as a significant risk factor for developing a CDAD in our department.     

Severe Clostridium difficile-associated disease in populations previously at low risk--four states, 2005

Clostridium difficile is a spore-forming, gram-positive bacillus that produces exotoxins that are pathogenic to humans. C. difficile-associated disease (CDAD) ranges in severity from mild diarrhea to fulminant colitis and death. Antimicrobial use is the primary risk factor for development of CDAD because it disrupts normal bowel flora and promotes C. difficile overgrowth. C. difficile typically has affected older or severely ill patients who are hospital inpatients or residents of long-term-care facilities. Recently, however, both the frequency and severity of health-care-associated CDAD has increased; from 2000 to 2001, the rate of U.S. hospital discharge diagnoses of CDAD increased by 26%. One possible explanation for these increases is the emergence of a previously uncommon strain of C. difficile responsible for severe hospital outbreaks. Although individual cases of CDAD are not nationally reportable, in 2005, the Pennsylvania Department of Health (PADOH) and CDC received several case reports of serious CDAD in otherwise healthy patients with minimal or no exposure to a health-care setting. An investigation was initiated by the Philadelphia Department of Public Health (PDPH), PADOH, and CDC to determine the scope of the problem and explore a possible change in CDAD epidemiology. This report summarizes the results of the investigation in Pennsylvania and three other states, which indicated the presence of severe CDAD in healthy persons living in the community and peripartum women, two populations previously thought to be at low risk. The findings underscore the importance of judicious antimicrobial use, the need for community clinicians to maintain a higher index of suspicion for CDAD, and the need for surveillance to better understand the changing epidemiology of CDAD.     

难辨梭菌相关性疾病临床危险因素的研究

目的 分析难辨梭菌相关性疾病(CDAD)的临床治疗和用药危险因素,为遏止CDAD发病上升趋势,降低医疗成本提供依据.方法 对45例CDAD患者与85例非CDAD患者病例进行回顾性对照研究;比较两组患者在治疗药物、措施:胃肠道手术、灌肠术,实验室化验指标:白细胞、白蛋白的差异;各研究变量先进行单因素分析,有统计学差异的纳入logistic回归模型进行多因素分析.结果 回归模型显示,头孢菌素类:OR=3.321,95％CI:1.54～7.14,β=1.647、喹诺酮类OR=2.438,95％CI:1.15～5.15,β=1.255、糖肽类OR=0.232,95％CI:0.06～0.83,β=-2.130,抗菌药物的使用与CDAD存在显著性相关性(P＜0.05).结论 头孢菌素类、喹诺酮类抗菌药物的不合理使用,是导致CDAD发生的主要危险因素,糖肽类药物使用可以作为预防CDAD发生的保护性因素.     

Costs of nosocomial Clostridium difficile-associated diarrhoea

Nosocomial Clostridium difficile-associated disease (CDAD) is a common infection in hospitals. A matched case-control study was carried out to determine hospital-wide excess costs due to CDAD. Cases were assessed by prospective hospital-wide surveillance in a tertiary care university hospital in 2006. Nosocomial cases of CDAD (>72h after admission) were matched to control patients without CDAD in a ratio 1:3 using the same diagnosis-related group in the same year, for a hospital stay at least as long as the time of risk of the CDAD cases before infection and a Charlson comorbidity index +/-1. Data on overall costs per case were provided by the finance department. Matching was possible for 45 nosocomial CDAD cases. The difference in the length of stay showed that CDAD cases stayed significantly longer (median 7 days; P=0.006) than their matched controls. The average cost per CDAD patient was euro33,840. The difference in the cost per patient showed that the cost for CDAD patients was significantly more than for their matched controls (median euro7,147; 95% confidence interval: 4,067-9,276). Nosocomial CDAD is associated with high costs for healthcare systems. Clinicians should be aware of the financial impact of this disease and the application of appropriate infection control measures is recommended to reduce spread.     

Risk factors for acquisition of Clostridium difficile-associated diarrhea among outpatients at a cancer hospital.

BACKGROUND: Clostridium difficile-associated diarrhea (CDAD) is an important infection in hospital settings. Its impact on outpatient care has not been well defined. OBJECTIVE: To examine risk factors of ambulatory cancer patients with CDAD. DESIGN: Case-control study. SETTING: Memorial Sloan-Kettering Cancer Center, a tertiary-care hospital. METHODS: Cases of CDAD among oncology outpatients from January 1999 through December 2000 were'identified via positive C. difficile toxin assay results on stool specimens sent from clinics or the emergency department. A 1:3 matched case-control study examined exposures associated with CDAD. RESULTS: Forty-eight episodes of CDAD were identified in cancer outpatients. The mean age was 51 years; 44% were female. Forty-one (85%) had received antibiotics within 60 days of diagnosis, completing courses a median of 16.5 days prior to diagnosis. Case-patients received longer courses of first-generation cephalosporins (4.8 vs 3.2 days; P = .03) and fluoroquinolones (23.6 vs 8 days; P < .01) than did control-patients. Those receiving clindamycin were 3.9-fold more likely to develop CDAD (P < .01). For each additional day of clindamycin or third-generation cephalosporin exposure, patients were 1.29- and 1.26-fold more likely to develop CDAD (P < .01 and .04, respectively). The 38 CDAD patients hospitalized during the risk period (79.2%) spent more time as inpatients than did control-patients (19.3 vs 9.7 days; P < .001). CONCLUSIONS: Antibiotic use, especially with cephalosporins and clindamycin, and prolonged hospitalization contributed to the development of CDAD. Outpatient CDAD appears to be most strongly related to inpatient exposures; reasons for the delayed development of symptoms are unknown.     

Increase in adult Clostridium difficile-related hospitalizations and case-fatality rate, United States, 2000-2005

Virulence of and deaths from Clostridium difficile-associated disease (CDAD) are on the rise in the United States. The incidence of adult CDAD hospitalizations doubled from 5.5 cases per 10,000 population in 2000 to 11.2 in 2005, and the CDAD-related age-adjusted case-fatality rate rose from 1.2% in 2000 to 2.2% in 2004.     

Clostridium difficile-associated disease in Oregon: increasing incidence and hospital-level risk factors.

BACKGROUND: The incidence of Clostridium difficile-associated disease (CDAD) appears to be increasing. Population-based estimates of disease have been limited, and analyses of hospital-level risk factors for CDAD are lacking. We sought to determine the incidence and trends of CDAD in Oregon and to identify hospital-level factors associated with increases in disease. METHODS: We analyzed hospital discharge data to calculate the incidence and to describe trends of CDAD in Oregon from 1995 through 2002. We administered questionnaires to hospital laboratory directors, infection control practitioners, and pharmacists to determine the status of laboratory, infection control, and pharmacy policies over time. RESULTS: The overall incidence of CDAD in Oregon was 3.5 case patients per 10,000 residents in 2002. Incidence increased from 1.4 to 3.3 cases per 1,000 hospital discharges from 1995 to 2002. Rates of disease increased most in hospitals with licensed bed capacity of more than 250 beds and more than 5 intensive care unit beds. Few laboratories, infection control practitioners, and pharmacists were able to identify changes in specific policies over the study period. CONCLUSIONS: This is the first study to determine a statewide population-based incidence of CDAD. Incidence of CDAD in Oregon has more than doubled over the past decade; larger hospitals experienced the greatest increase in disease rates. We did not identify hospital-level policies that could explain the increase. A study of patients with CDAD at the hospitals with the largest increases is underway to further identify risk factors.     

Changing epidemiology of Clostridium difficile-associated disease in children.

OBJECTIVE: To determine temporal trends in the incidence rate for Clostridium difficile-associated disease (CDAD) in a pediatric patient population. METHODS: We performed an observational, retrospective cohort study that included children who visited or were admitted to Children's National Medical Center during the period from July 2001 through June 2006. The CDAD incidence rates were determined and examined for changes over time using the Poisson regression method. RESULTS: A total of 513 patients whose stool specimens tested positive for C. difficile toxin were identified. Of these patients, 61% were children aged 2 years or older. The proportion of patients with CDAD in this age group has steadily increased from 46% in 2001 to 64% in 2006. Largely as a result of an increasing number of cases of community-associated CDAD, the incidence of CDAD increased significantly in the outpatient setting, particularly in the emergency department (1.18 cases per 1,000 visits in 2001 vs 2.47 cases per 1,000 visits in 2006; P=.02). The incidence among inpatients decreased during the study period (1.024 cases per 1,000 patient-days in 2001 vs 0.680 cases per 1,000 patient-days in 2006; P=.004). In the neonatal intensive care unit, C. difficile toxin was detected in stool specimens collected from 22 patients aged from 15 days to 6 months. CONCLUSION: This study revealed a steady increase in the number of patients seen in the emergency department with community-acquired CDAD. Findings from this study suggest that the characteristics of CDAD in children--a population that has not been considered to be at high risk for this disease in the past--are changing. Further investigations are warranted to explore deviations from the established burdens of the disease and patient risk factors.     

Fluoroquinolones and risk for methicillin-resistant Staphylococcus aureus, Canada

Receipt of fluoroquinolones was the predominant risk factor for Clostridium difficile-associated disease (CDAD) during an epidemic in Quebec, Canada. To determine the role of antimicrobial drugs in facilitating healthcare-associated methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection and to compare this role with their effects on methicillin-susceptible S. aureus infection and CDAD, we conducted a retrospective cohort study of patients in a Quebec hospital. For 7371 episodes of care, data were collected on risk factors, including receipt of antimicrobial drugs. Crude and adjusted hazard ratios (AHR) were calculated by Cox regression. Of 150 episodes of MRSA colonization and 23 of MRSA infection, fluoroquinolones were the only antimicrobials that increased risk for colonization (AHR 2.57, 95% confidence interval [CI] 1.84-3.60) and infection (AHR 2.49, 95% CI 1.02-6.07). Effect of antimicrobial drugs on MRSA colonization and infection was similar to effect on CDAD and should be considered when selecting antimicrobial drugs to treat common infections.     

Quinolone use as a risk factor for nosocomial Clostridium difficile-associated diarrhea.

OBJECTIVE: To determine modifiable risk factors for nosocomial Clostridium difficile-associated diarrhea (CDAD). DESIGN: Case-control study. SETTING: 300-bed tertiary-care hospital. PARTICIPANTS: Hospital inpatients present during the 3-month study period. METHODS: Case-patients identified with nosocomial CDAD over the study period were compared to two sets of control patients: inpatients matched by age, gender, and date of admission; and inpatients matched by duration of hospital stay. Variables including demographic data, comorbid illnesses, antibiotic exposure, and use of gastrointestinal medications were assessed for case- and control-patients. Conditional logistic regression was performed to identify risk factors for nosocomial CDAD. RESULTS: 27 case-patients were identified and were compared to the two sets of controls (1:1 match for each comparison set). For the first set of controls, use of ciprofloxacin (odds ratio [OR], 5.5; 95% confidence interval [CI 95], 1.2-24.8; P=.03) was the only variable that remained significant in the multivariable model. For the second set of controls, prior exposure to cephalosporins (OR, 6.7; CI 95, 1.3-33.7; P=.02) and to ciprofloxacin (OR, 9.5; CI 95, 1.01-88.4; P=.05) were kept in the final model. CONCLUSIONS: Along with cephalosporins, prior quinolone use predisposed hospitalized patients to nosocomial CDAD. Quinolones should be used judiciously in acute-care hospitals, particularly in those where CDAD is endemic.     

Clostridium difficile among hospitalized patients receiving antibiotics: a case-control study.

OBJECTIVES: Clostridium difficile is the most common cause of infectious nosocomial diarrhea and can be found in up to 30% of asymptomatic hospitalized patients. Our primary aim was to compare the clinical characteristics of hospitalized patients who received antibiotics and developed C. difficile-associated diarrhea (CDAD) with those of hospitalized patients who received antibiotics and did not develop the disease. DESIGN: Case-control study comprising inpatients at a single institution. PATIENTS: Case-patients were defined as patients who had diarrhea and tested positive for C. difficile. Control-patients (matched 4:1 to case-patients) were defined as patients who received antibiotics for at least 5 days and did not develop CDAD. RESULTS: On univariate analysis, nine variables were associated with CDAD. Only three of the variables, need for intensive care, length of stay, and macrolide antibiotic use, were found to be significant (P < .05) on logistic regression analysis. The odds ratios for status as a CDAD case were 3.68 (CI95, 1.44 to 9.40) for stay in the intensive care unit and 1.03 (CI95, 1.02 to 1.05) for each day of hospital stay. Receipt of macrolide antibiotics reduced risk significantly; the odds ratio was 0.23 (CI95, 0.19 to 0.87). CONCLUSIONS: We identified need for intensive care and length of stay as important risk factors for the development of CDAD. We also identified macrolide antibiotic use as protective against its development. Patients receiving intensive care may represent a population to study for targeted prophylaxis.     

Antibiotic prophylaxis and the risk of Clostridium difficile-associated diarrhoea.

To test the hypothesis that extended antibiotic prophylaxis increases the risk of Clostridium difficile -associated diarrhoea (CDAD), we conducted a retrospective cohort study of 2641 patients under-going cardiovascular surgery. Main outcome measures were the duration of prophylaxis (< 48 h vs. > 48 h) and the occurrence of CDAD. CDAD occurred in 31 patients (1.2%), who were significantly older (70 +/- 9 y vs. 66 +/- 10 y; P = 0.03), received more therapeutic antibiotics (2.2 +/- 1.9 vs. 0.4 +/- 0.9; P = 0.001) and had a longer postoperative hospital stay (26 +/- 19 d vs. 9 +/- 8 d; P < 0.001) than non-cases. After adjusting for confounding, we did not observe an association between prolonged prophylaxis and CDAD [adjusted odds ratio (AOR), 0.8; CI, 0.4-1.8]. In contrast, three independent predictors were identified: increasing length of hospital stay (AOR per one-day-increment, 1.03; CI, 1.01-1.05), and treatment with third generation cephalosporins (AOR, 5.9; CI, 2.2-16.0) or beta-lactam-beta-lactamase inhibitor combinations (AOR, 4.6; CI, 1.7-12.3). Our results did not confirm that extended prophylaxis after clean surgery increases the risk of CDAD, which remains an uncommon postoperative complication, associated even with short antibiotic exposure.