Incidence Of Clostridium Difficile-associated Diarrhea Research Articles

Clostridium difficile-associated diarrhea in radiooncology: an underestimated problem for the feasibility of the radiooncological treatment?

Background and PurposeOver the last years an increasing incidence of Clostridium difficile-associated diarrhea (CDAD) has been reported. Especially haematology-oncology patients are at risk of developing CDAD.The aim of this analysis is to determine the incidence of CDAD in radiooncological patients and to find out what relevance CDAD has for the feasibility of the radiooncological treatment, as well as to detect and describe risk factors.Patients and MethodsIn a retrospective analysis from 2006 to 2010 34 hospitalized radiooncological patients could be identified having CDAD. The risk factors of these patients were registered, the incidence was calculated and the influence on the feasibility of the radiooncological therapy was evaluated. Induced arrangements for prophylaxis of CDAD were identified and have been correlated with the incidence.ResultsThe incidence of CDAD in our collective is 1,6%. Most of the patients suffering from a CDAD were treated for carcinoma in the head and neck area. Common risk factors were antibiotics, proton pump inhibitors, cytostatic agents and tube feeding.Beside a high rate of electrolyte imbalance and hypoproteinemia a decrease of general condition was frequent. 12/34 patients had a prolonged hospitalization, in 14/34 patients radiotherapy had to be interrupted due to CDAD. In 21 of 34 patients a concomitant chemotherapy was planned. 4/21 patients could receive all of the planned cycles and only 2/21 patients could receive all of the planned cycles in time.4/34 patients died due to CDAD. In 4/34 patients an initially curative treatment concept has to be changed to a palliative concept.With intensified arrangements for prophylaxis the incidence of CDAD decreased from 4,0% in 2007 to 0,4% in 2010.ConclusionThe effect of CDAD on the feasibility of the radiotherapy and a concomitant chemotherapy is remarkable. The morbidity of patients is severe with a high lethality.Reducing of risk factors, an intense screening and the use of probiotics as prophylaxis can reduce the incidence of CDAD.

The impact of hospital antimicrobial policy on the incidence of Clostridium difficile infection

Abstract Focal points

Clostridium difficile-associated disease among patients in Dhahran, Saudi Arabia

Clostridium difficile-associated diarrhea (CDAD) is an important healthcare-associated infection. However, there are no data from Saudi Arabia on this disease. A two-year prospective, observational study on the incidence of CDAD in a hospital in Saudi Arabia was carried out. Stool analysis for C. difficile toxins A and B was carried out by an enzyme-linked immunosorbent assay. Medical and laboratory records were reviewed. Of the total number of patients, there were 53.3% male and the mean age was 44.6 ± 27.2 years. Of the 913 specimens, only 42 (4.6%) were positive for C. difficile toxins. The annual incidence rates of C. difficile were 1.2 and 0.9 per 1000 discharges, and 2.4 and 1.7 per 10,000 patient days in 2007 and 2008, respectively. Of the total number of cases, 52.4% were with onset in the hospital, 38.1% were with onset in the community and 9.5% were community-onset but healthcare facility-associated CDAD. Of the cases, 16 (39%) patients did not have exposure to antimicrobial drugs in the 3 months prior to the test date. The remaining patients received antimicrobial drug therapy. Cephalosporin and fluoroquinolone were the most common antimicrobial drugs used. Overall, the prevalence of C. difficile-associated diarrhea was low; further studies are required in Saudi Arabia to elucidate the true prevalence of the disease.

A Meta-analysis of 16 Observational Studies on Proton Pump Inhibitor Use and Risk of Clostridium difficile Associated Diarrhea

Purpose:Clostridium difficile associated diarrhea (CDAD) is a major cause of morbidity and increasing health care costs among hospitalized patients. While exposure to antibiotics remains the most documented risk factor for CDAD, attention has recently been directed towards a plausible link with proton pump inhibitors (PPIs). However, the results of studies on the association between CDAD and PPIs remain controversial. We have conducted a meta-analysis addressing the association between PPIs and CDAD among hospitalized patients on the general medicine floor. Methods: A systematic search of published literature on studies that investigated the association between PPIs and CDAD from 1980-2010 was conducted on Medline and PubMed. The identified articles were reviewed for additional references. The most adjusted risk estimates were extracted by two authors and summarized using random effects meta-analysis. We also conducted a stratified analysis by study design. All studies were evaluated for publication bias before the analysis. Results: Sixteen studies involving more than 1.2 million patients met the inclusion criteria. There was a 65% (summary risk estimate 1.65 with a 95% Confidence interval (CI) from 1.50 to 1.81; P <0,001) increase in the incidence of CDAD among patients on proton pump inhibitors. By study design, whether prospective (5) or retrospective (11), there was still a significant increase in the incidence of CDAD among PPI users. The risk estimates were 1.34(95% CI from 1.32 to 1.65; P<0.001) and 2.17(95% CI from 1.86 to 2.52; P<0.001) for cohort and case-control studies respectively. There was no evidence of publication bias. Conclusion: There is sufficient evidence to suggest that proton pump inhibitors increase the incidence of CDAD. Our meta-analysis show a 65% increase in the incidence of CDAD among PPI users. We recommend that the routine use of PPIs for gastric ulcer prophylaxis be discouraged, and should be based on current guidelines.

An outbreak case of Clostridium difficile-associated diarrhea among elderly inpatients of an intensive care unit of a tertiary hospital in Rio de Janeiro, Brazil

The aim of this study was to investigate Clostridium difficile-associated diarrhea (CDAD) in an intensive care unit (ICU) of a tertiary hospital in Rio de Janeiro, Brazil, and to characterize epidemiologically C. difficile strains obtained from an outbreak of CDAD. Within almost a 4-year surveillance period, CDAD incidence was determined for the first time in Brazil, and a 3-fold increase was observed in the average rate of CDAD, featuring an outbreak. About 80% of the patients were over 65 years. The main antibiotic that could be probably associated to CDAD was piperacillin/tazobactam. Four toxigenic strains were isolated, 3 from stools and 1 from environmental samples. They were all resistant to clindamycin and fluoroquinolones. Fingerprinting analysis revealed their distribution between 2 different polymerase chain reaction ribotypes, with one of them being exclusively found in Brazil. It was possible to detect cross-infection and environmental contamination in the ICU. Our results highlight the importance of a continuous CDAD surveillance in the hospitals, especially when a risk group is exposed.

Pseudo-outbreak of Clostridium difficile associated diarrhea (CDAD) in a tertiary-care hospital

The objective of this study was to describe a pseudo-outbreak of C. difficile in a hospital, following a change in the method used to detect the toxin. In February 2002, there were two cases of CDAD and in March 7 occurred, coinciding with a change of the test (from detection of toxin A to toxin A/B). An outbreak was suspected. Active surveillance and education of staff were started. A CDAD case was defined as a patient with acute onset of diarrhea (> or = three episodes of liquid stools) and a positive stool test. They were classified as hospital or community-acquired. Stool samples were also collected for C. difficile culture and isolates were typed using AP-PCR. From March 2002 through December 2003 there were 138 cases of CDAD: 70% were hospital-acquired and among the 30% with CDAD present on admission, most (81%) came directly from the community (50% had no history of hospitalization). Fifty-two percent of hospital-acquired CDAD and 94% of cases on admission had already used antibiotics. The incidence of CDAD in hospitalized patients during surveillance was 3.3 per 1000 patient-admissions. The incidence of CDAD present on admission was 6.1/1000 patients. Sixteen isolates were typed and presented 13 different profiles. In conclusion, the CDAD increase in our study occurred due to change in diagnostic methods and not due to an outbreak, as suspected initially. The incidence in hospitalized patients was much lower than in reported outbreaks. There were 13 molecular types suggesting that an outbreak did not occur. CDAD was largely community-acquired.

Identification of Risk Factors for the Development of Clostridium difficile-Associated Diarrhea Following Treatment of Polymicrobial Surgical Infections

To identify risk factors for Clostridium difficile-associated diarrhea (CDAD) in surgical patients following treatment of polymicrobial infections. Infections among surgical patients are frequently anaerobic or mixed aerobic-anaerobic infections and are therefore subject to polymicrobial antibiotic coverage, including metronidazole. While multiple antibiotics are known to contribute to the development of CDAD, the role of preventive antibiotics is unproven. An 11-year dataset of consecutive infections treated in surgical patients at a single hospital was reviewed. All intra-abdominal, surgical site, or skin/skin structure infections were identified. Each infection was evaluated for antibiotic coverage and subsequent CDAD. Antibiotic usage was assessed using chi analysis. A multiple logistic regression was used to identify independent predictors of CDAD. A total of 4178 intra-abdominal, surgical site, or skin/skin structure infections were identified. Of these infections, 98 were followed by CDAD. Only carbapenem use affected the incidence of CDAD: 3.5% of infections treated with a carbapenem were followed by CDAD, whereas only 2.1% of infections treated without carbapenems were followed by CDAD (P = 0.04). Metronidazole had no association with future CDAD. Only age and Acute Physiology and Chronic Health Evaluation II (APACHE II) score were independently associated with CDAD by multiple logistic regression analysis. Older patients with a high severity of illness are at greatest risk for developing CDAD following treatment of polymicrobial infections. No specific antibiotic class, including fluoroquinolones, is associated with an increased incidence of CDAD in this population. Although use of metronidazole in the treatment of polymicrobial infections is appropriate for anaerobic coverage, it does not reduce the risk of future CDAD.

Safety Considerations of Fluoroquinolones in the Elderly

The fluoroquinolones ciprofloxacin, levofloxacin, moxifloxacin and gemifloxacin are widely used for the treatment of various types of bacterial infections. Overall, these antibacterial agents can be considered safe and well tolerated drugs. Comparative studies have evaluated the use of quinolones in elderly and younger populations. Although age per se does not seem to decrease their tolerability, specific adverse effects of the quinolones must be considered when they are chosen for antibacterial treatment. Renal function declines consistently with age and doses of renally excreted quinolones (e.g. ofloxacin, levofloxacin, gatifloxacin) need to be adjusted if a clinically relevant reduction of creatinine clearance is identified. Reactions of the gastrointestinal tract, such as nausea, dyspepsia, vomiting or diarrhoea, are among the most often registered adverse drug reactions during therapy with fluoroquinolones. Treatment with a quinolone causes diarrhoea less frequently than treatment with other classes of antimicrobials. Conflicting data have been published with respect to the incidence of Clostridium difficile-associated diarrhoea in quinolone-treated patients. Hypersensitivity reactions, often manifested on the skin, occur less commonly during therapy with quinolones than, for example, during therapy with beta-lactam antibacterials. Adverse reactions of the CNS are of particular concern in the elderly population. Given the CNS excitatory effects of quinolones, elderly patients should be monitored carefully for such symptoms. It is likely that many signs of possible adverse reactions, such as confusion, weakness, loss of appetite, tremor or depression, are often mistakenly attributed to old age and remain unreported. Quinolones should be used with caution in patients with known or suspected CNS disorders that predispose to seizures (e.g. severe cerebral arteriosclerosis or epilepsy). Quinolones can cause QT interval prolongation. They should be avoided in patients with known prolongation of the QT interval, patients with uncorrected hypokalaemia or hypomagnesaemia and patients receiving class IA (e.g. quinidine, procainamide) or class III (e.g. amiodarone, sotalol) antiarrhythmic agents. Tendinitis and tendon ruptures are recognized as quinolone-induced adverse effects that can occur during treatment or as late as several months after treatment. Chronic renal diseases, concomitant use of corticosteroids and age >60 years are known risk factors for quinolone-induced tendopathies. Overall, the specific adverse-effect profile of quinolones must be considered when they are chosen for treatment of bacterial infections. Because of physiological changes in renal function and when certain co-morbidities are present, some special considerations are necessary when elderly patients are treated with these drugs.

Dose–Response Efficacy of a Proprietary Probiotic Formula of Lactobacillus acidophilus CL1285 and Lactobacillus casei LBC80R for Antibiotic-Associated Diarrhea and Clostridium difficile -Associated Diarrhea Prophylaxis in Adult Patients

Standard therapies for antibiotic-associated diarrhea (AAD) and Clostridium difficile-associated diarrhea (CDAD) have limited efficacy. Probiotic prophylaxis is a promising alternative for reduction of AAD and CDAD incidence. In this single-center, randomized, double-blind, placebo-controlled dose-ranging study, we randomized 255 adult inpatients to one of three groups: two probiotic capsules per day (Pro-2, n=86), one probiotic capsule and one placebo capsule per day (Pro-1, n=85), or two placebo capsules per day (n=84). Each probiotic capsule contained 50 billion c.f.u. of live organisms (Lactobacillus acidophilus CL1285 +Lactobacillus casei LBC80R Bio-K+ CL1285). Probiotic prophylaxis began within 36 h of initial antibiotic administration, continued for 5 days after the last antibiotic dose, and patients were followed for an additional 21 days. Pro-2 (15.5%) had a lower AAD incidence vs. Pro-1 (28.2%). Each probiotic group had a lower AAD incidence vs. placebo (44.1%). In patients who acquired AAD, Pro-2 (2.8 days) and Pro-1 (4.1 days) had shorter symptom duration vs. placebo (6.4 days). Similarly, Pro-2 (1.2%) had a lower CDAD incidence vs. Pro-1 (9.4%). Each treatment group had a lower CDAD incidence vs. placebo (23.8%). Gastrointestinal symptoms were less common in the treatment groups vs. placebo and in Pro-2 vs. Pro-1. The proprietary probiotic blend used in this study was well tolerated and effective for reducing risk of AAD and, in particular, CDAD in hospitalized patients on antibiotics. A dose-ranging effect was shown with 100 billion c.f.u., yielding superior outcomes and fewer gastrointestinal events compared to 50 billion c.f.u. (ClinicalTrials.gov number NCT00958308).

Proton Pump Inhibitor Therapy Alleged Accomplice or Innocent Bystander in the Changing Epidemiology of Clostridium Difficile Associated Diarrhea?

Purpose: Over the past decade there has been an increase in the number of hospital patients with Clostridium difficile-associated diarrhea (CDAD). It has become a major hospital acquired pathogen and understanding the potential risk factors for CDAD has become an important focus of research. One of the controversial associations commonly stated of increasing ones risk of acquiring CDAD is proton pump inhibitor (PPI) therapy (Am J Gastroenterol 2008; 103:2308-2313). This retrospective chart review study was done to evaluate the incidence of CDAD in hospitalized patients who were taking PPI therapy. Methods: An IRB approved retrospective case-control chart review study was conducted consisting of 209 randomly chosen hospitalized patients charts admitted between 1/01/05 to 7/01/08 that were found to have a discharge diagnosis of CDAD by ICD9 coding (008.45). Charts were then analyzed for inclusion criteria to determine if patients had a positive C.difficile cytotoxin assay performed during that admission, if PPI therapy was used continuously for at least three days prior to that positive cytotoxin stool assay, and whether the patients were over the age of eighteen. Exclusion criteria for the study consisted of having no prior history of CDAD within the past 6 months. In addition, a randomly chosen age and gender matched control group of 168 charts was obtained during the same time frame, with the only inclusion/exclusion criteria required be that the patient be above the age of eighteen, with no diarrhea symptoms while in the hospital and no positive C. difficle cytotoxin assays during admission. Results: Of the 209 hospitalized patient charts reviewed, 149 met the inclusion criteria for the study while 60 were excluded. Cases were not found to be more likely than controls to have acid suppressive therapy with PPI onboard while admitted to the hospital, 80 (53.7%) vs. 99 (58.9%) with a P=0.8081 by Cochran-Mantel-Haenszel analysis. Conclusion: This retrospective study further argues against the alleged risk factor association that PPI therapy will increase a hospitalized patient's chance for developing CDAD due to gastric acid suppression. Further randomized prospective studies should be sought to further clarify this discrepancy in correlation.

Relationship between Antibiotic Consumption and Clostridium difficile -Associated Diarrhea: an Epidemiological Note

In a recent study, Aldeyab et al. determined the hospital-wide relationship between antimicrobial drug consumption and occurrence as well as spread of Clostridium difficile-associated diarrhea (CDAD) in a teaching hospital in Belfast, Northern Ireland (1). A major advantage of the methods used (time series analysis) is the establishment of a hospital-wide cause-effect relationship, with a clear direction and determination of the strength of the observed correlation. We compared the study results reported by Aldeyab et al. with data from a 1,600-bed teaching hospital in Freiburg, Germany, and found comparable dose-response rates for the two studies (1, 4). The dose-response relationship between antibiotic consumption and emergence of resistance was first described in 1989 by Phelps, who defined this relationship as “the percentage change in the probability of an organism being resistant following a 1% change in the level of antibiotic use” (6). In economic science, the time series analysis is used extensively for analysis of economic relationships (econometrics). In this context, the dose-response rate is termed elasticity and can easily be deduced from the coefficients estimated by time series analyses (3). In the studies conducted by Aldeyab et al., elasticity ECDAD,q is defined as (1) where CDAD(q) stands for the incidence of CDAD, which is a dependent function of the consumption of q. The variable q represents the independent variable used in the time series analysis, i.e., a series associated with the consumption of a class of antimicrobials. Following this concept, the coefficients estimated by Aldeyab et al. can be transformed into elasticities, thus facilitating comparisons between different study settings. First, estimated coefficients are inserted into the first fraction of equation 1 [∂CDAD(q)/∂q]. Second, averages of the dependent variable CDAD and the independent variable q (i.e., antibiotic use series) are inserted into the second fraction [q/CDAD(q)]. In contrast, the study conducted in Southern Germany used a log-linear modeling approach for the estimation of the multivariate model (4). According to this, elasticity ECDAD,q is defined as (2) which means that all estimated coefficients may be interpreted as dose-response rates without transformation. For the two studies investigated here, elasticities are shown in Table ​Table1.1. A 1% increase in the use of fluoroquinolones in Belfast, for instance, was followed by a 0.4% increase in the incidence of CDAD, while a 1% increase in the use of fluoroquinolones in Freiburg was followed by a 1% increase in the incidence of CDAD. TABLE 1. Coefficients estimated by time series analyses for Belfast and Freiburg and their corresponding elasticitiesa Unfortunately, both studies do not distinguish between community-acquired and health care-associated cases of CDAD. Therefore, both analyses may be biased by a proportion of patients admitted with CDAD whose diarrhea was not caused by prior in-hospital antibiotic use. Differences in this proportion could act as an explanation for differences in the dose-response rates. An analysis of the influence of Clostridium difficile colonization pressure from outside the hospital that includes the incidence of patients admitted with CDAD as an independent variable would be a challenge for future analyses in the same way as was recently done for methicillin-resistant Staphylococcus aureus and extended-spectrum-β-lactamase-producing strains (2, 4, 5).

Quasiexperimental Study of the Effects of Antibiotic Use, Gastric Acid-Suppressive Agents, and Infection Control Practices on the Incidence of Clostridium difficile -Associated Diarrhea in Hospitalized Patients

The objective of this study was to evaluate the effects of antimicrobial drug use, gastric acid-suppressive agent use, and infection control practices on the incidence of Clostridium difficile-associated diarrhea (CDAD) in a 426-bed general teaching hospital in Northern Ireland. The study was retrospective and ecological in design. A multivariate autoregressive integrated moving average (time-series analysis) model was built to relate CDAD incidence with antibiotic use, gastric acid-suppressive agent use, and infection control practices within the hospital over a 5-year period (February 2002 to March 2007). The findings of this study showed that temporal variation in CDAD incidence followed temporal variations in expanded-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.01/100 bed-days), broad-spectrum cephalosporin use (average delay = 2 months; variation of CDAD incidence = 0.02/100 bed-days), fluoroquinolone use (average delay = 3 months; variation of CDAD incidence = 0.004/100 bed-days), amoxicillin-clavulanic acid use (average delay = 1 month; variation of CDAD incidence = 0.002/100 bed-days), and macrolide use (average delay = 5 months; variation of CDAD incidence = 0.002/100 bed-days). Temporal relationships were also observed between CDAD incidence and use of histamine-2 receptor antagonists (H2RAs; average delay = 1 month; variation of CDAD incidence = 0.001/100 bed-days). The model explained 78% of the variance in the monthly incidence of CDAD. The findings of this study highlight a temporal relationship between certain classes of antibiotics, H2RAs, and CDAD incidence. The results of this research can help hospitals to set priorities for restricting the use of specific antibiotic classes, based on the size-effect of each class and the delay necessary to observe an effect.

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

BackgroundClostridium 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. MethodsWe 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. ResultsThe 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 5C. difficile strains available for extensive identification. ConclusionThe 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.

Surveillance of Clostridium difficile-associated diarrhoea with the German nosocomial infection surveillance system KISS (CDAD-KISS)

A study of 2856 Clostridium difficile -associated diarrhoea (CDAD) patients from 34 hospitals in Germany was carried out over a period of 12 months in 2007. The overall incidence of CDAD cases was 46.5 per 10,000 admitted patients, or 6.6 cases per 10,000 patient-days. Seventy-three percent of cases were considered to be nosocomial and 8.4% were classified as severe. There was a wide range in the incidence of CDAD between the hospitals (interquartile range [IQR] 3.2–9.2 cases per 10,000 patient-days), and the incidence of nosocomial cases (IQR 1.7–6.7 per 10,000 patient-days). The differences between the hospitals were in line with the differences in local diagnostic and infection control procedures. The overall incidence in the hospitals participating in the surveillance system was much higher than that in the discharge data from the whole of Germany in 2006. This may be due to more diligent ICD9 coding by the clinicians during an active surveillance strategy. However, the group of hospitals participating in the study was small and may not be representative of the situation in the country as a whole.

Increasing incidence of Clostridium difficile-associated diarrhea in inflammatory bowel disease

Introduction and aimOver the last decade a rise in Clostridium difficile-associated diarrhea (CDAD) has been observed. A higher incidence of CDAD has also been suggested in patients with inflammatory bowel disease (IBD), and may be a challenging factor in the differential diagnosis of flares. It is unclear if the increase is caused by the enhanced use of immunosuppressive therapy in IBD. We investigated if CDAD infection is increasing in IBD patients and evaluated outcome and possible predisposing factors. MethodsThrough an electronic database of the Laboratory of Microbiology of our hospital (tertiary referral center), all stool samples from patients admitted for diarrhea and hospitalized on gastroenterology wards between January 2000 and January 2008 were reviewed for diagnosis of CDAD. For analysis, we compared two periods of equal duration. ResultsA total of 57 patients were diagnosed with CDAD, of whom 26.3% had concomitant IBD. A 3.75-fold increase in CDAD was observed between period 1 and period 2, irrespective of underlying IBD and with a comparable total number of analyzed stool samples between both periods. Non-IBD patients were significantly older. Antibiotic use three months prior to the infection was higher in non-IBD (29/42 or 69%) than in IBD patients (6/15 or 42%) (p = 0.047). Nine IBD patients were on concomitant immunomodulators, and this was not different between period 1 and period 2. Most patients had a successful outcome and only one patient with ulcerative colitis needed semi-urgent colectomy. Two patients died in the non-IBD group. The duration of hospital stay was significantly lower in IBD patients. ConclusionWe observed a significant rise in CDAD in both IBD and non-IBD. The clinical outcome was favorable with only one IBD patient needing semi-urgent colectomy. Because C. difficile can mimic an IBD flare, it is essential that clinicians are vigilant to this complication. The use of immunosuppressive drugs in IBD does not influence the risk.

Efficacy of a Probiotic Fermented Drink of Lactobacillus Acidophilus and Lactobacillus Casei in the Reduction of Antibiotic-Associated Diarrhea

Purpose: To assess the efficacy and safety of a commercially available probiotic drink comprised of 50 × 109 billion L. acidophilus and L. casei, Bio-K+ CL1285® (Bio-K+) in reducing Antibiotic-Associated Diarrhea (AAD) in patients on antibiotic regime who were initially treated in a hospital setting. Methods: This was a randomized, double blind, placebo controlled trial. Adults patients who were prescribed antibiotics for 3 –14 days were enrolled from eight Canadian centers. Study treatment was randomized at a 1:1 ratio of Bio-K+ or placebo and was administered within 24 hours of initiation to 5 days after termination of antibiotic therapy. Patients were followed for 21 days after the last dose of study treatment. The primary efficacy outcome measure was the occurrence and frequency of new onset AAD. The secondary outcome measure was the incidence of Clostridium Difficile-Associated Diarrhea (CDAD). Results: Among the 472 patients eligible for randomization there were 29 excluded because antibiotic treatment duration was less than 3 days and 6 because diarrhea onset was before initiation of study treatment. The ITT analysis was based on 437 (93%) of the eligible and enrolled patients in the study. The mean age of the patients in the study was approximately 60 years and 50% were male. The mean duration of antibiotic treatment was approximately 9 days and the mean duration of study treatment was approximately 12 days for both study groups. The mean (SD) number of diarrhea episodes was 1.19. (3.20) for the placebo and 0.67 (2.05) for Bio-K+ (P= 0.040). Multivariate linear regression results adjusting for duration of study treatment, duration of antibiotic therapy and patient's age showed that the duration of diarrhea for Bio-K+ versus placebo was reduced by 51.5% (b (SE) = 0.515 (0.256); P= 0.045). Multivariate logistic regression results showed that the adjusted odds ratio of diarrhea for Bio-K+ versus placebo was 0.627 (P= 0.037). The odd rations for diarrhea duration ≥ 2 and ≥ 3 days were 0.531 (P= 0.025) and 0.488 (P= 0.034) respectively. Four patients in the placebo group and one in the Bio-K+ group developed CDAD (P= 0.372). Study treatment was well tolerated and with similar low incidence of mild non serious adverse events similar in both groups. Conclusion: Probiotic prophylaxis of a commercially available fermented drink composed of 50 × 109 billion L. acidophilus and L. casei (Bio-K+ CL1285®) is well tolerated and effective in the reduction of the incidence and duration of AAD for patients receiving antibiotics that were initially treated in a hospital setting.

Measuring the incidence of Clostridium difficile-associated diarrhoea in a group of Western Australian hospitals

Clostridium difficile-associated diarrhoea (CDAD) is a well known healthcare-associated infection, increasing in incidence and severity in much of the developed world. Recommendations for surveillance of CDAD have been published, and CDAD incidence monitoring is increasingly recommended internationally, but unlike many other healthcare-associated infections, there is little comparative data available about CDAD rates in hospitalised patients in Australia. Nine hospitals in Western Australian used standardised definitions and methods to calculate CDAD incidence rates over a 6-month period in 2006, and tested the feasibility of using these protocols in a local context. The overall incidence rate of healthcare-associated CDAD was 1.2 per 10 000 occupied bed days (range 0–3.3 per 10 000 occupied bed days). Calculated rates and hospital rankings varied markedly if separations were used in place of occupied bed days. Each data collection form took a median of 10min to complete. The short study period and marked variation in laboratory diagnostic practices are limitations to direct comparison of rates between hospitals, but this is a useful and practical method of monitoring CDAD that can be easily incorporated in Australian infection control practice.

Rifamycin Antibiotics for Treatment of Clostridium difficile–Associated Diarrhea

To review the existing data on use of the rifamycin class of antibiotics as therapy for Clostridium difficile-associated diarrhea (CDAD). A literature search was performed using PubMed (1996-January 2008), abstracts from the International Conference on Antimicrobial Agents and Chemotherapy (September 2007), the Infectious Diseases Society of America (October 2007), Salix Pharmaceuticals Web site (January 2008), ActivBiotics Web site (January 2008), Google Scholar, and searches of selected bibliographies using the terms rifamycin, ansamycins, rifampin, rifabutin, rifampicin, rifaximin, rifalazil, Clostridium difficile, C. difficile, and CDAD. In vivo and in vitro studies investigating the use of rifamycins for CDAD were selected, along with all clinical trials using rifamycins in patients with CDAD. Nine studies totaling 890 isolates were identified that investigated the in vitro susceptibility of rifampin (6 studies), rifaximin (3 studies), and rifalazil (2 studies). Rifamycins consistently displayed potent activity against tested strains, although strains with decreased susceptibility have been identified. Six published clinical studies involving 81 patients have investigated the use of rifamycins for the treatment of CDAD. These have generally been small studies, although initial positive clinical results have been reported on the use of rifamycins for recurrent CDAD. Preliminary data support the use of rifamycins for treatment of CDAD. With the increased incidence and severity of CDAD, further investigation into this drug class as a treatment regimen for CDAD is warranted.

Evaluation of Clostridium difficile-associated diarrhea with a drug formulary change in preferred fluoroquinolones.

Recent publications report that gatifloxacin might be associated with a greater incidence of Clostridium difficile-associated diarrhea (C. difficile, CDAD) than are other fluoroquinolones. We performed a drug use evaluation to examine this issue after adding gatifloxacin to the formulary and changing from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone in 10 Department of Veterans Affairs (VA) medical centers in the northeastern United States. To estimate (1) the overall incidence of CDAD before and after the change from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone and (2) the incidence rates for ciprofloxacin, levofloxacin, and gatifloxacin separately. Using the VA's Pharmacy Benefits Management database, the total number of days of antibiotic therapy was determined for all inpatients and outpatients of the 10 medical centers who filled at least 1 antibiotic prescription between July 1, 2003, and June 30, 2004. This time frame was chosen because it included 6 months before and 6 months after the change in the preferred oral fluoroquinolone from levofloxacin to gatifloxacin for the VA health system on January 1, 2004. For the same study period and medical centers, the electronic medical records of all inpatients and outpatients with an entry for a positive C. difficile toxin were reviewed. Positive toxins that occurred within 6 weeks of a previous positive result in the same patient were excluded. Exact Poisson tests were used to compare the incidence rates of CDAD (number of CDAD cases per 1,000 days of antibiotic treatment) for antibiotics overall, the fluoroquinolones as a group, non-fluoroquinolone antibiotics, and the individual fluoroquinolones, com-paring the 6-month time periods before (pre-change) versus after (post-change) the addition of gatifloxacin as the preferred oral fluoroquinolone. Of 505 cases of CDAD in the 12-month study period, 413 (81.7%) were associated with antibiotic use in the previous 6 weeks. Among anti-biotic users, incidence rates of CDAD were 166 per 72,114 days of antibiotic therapy in the pre-change period (2.3 cases per 1,000 days of antibiotics) versus 247 per 72,354 days in the post-change period (3.4 cases per 1,000 days of antibiotics, P < 0.001). Fluoroquinolones accounted for 54.8% of the CDAD cases in the pre-change period and 67.2% in the post-change period, representing a 22.6% relative increase in the percentage of CDAD cases that were associated with fluoroquinolone use. The CDAD incidence rates per 1,000 days of fluoroquinolone therapy were 3.7 in the pre-change period versus 7.0 in the post-change period (P < 0.001). Among fluoroqui-nolone users, gatifloxacin accounted for none of the cases of CDAD in the pre-change period when it was nonformulary and 65.1% of the cases in the post-change period, for an incidence rate of 7.6 (108 per 14,239 days). The CDAD incidence rates per 1,000 antibiotic days for patients treated with ciprofloxacin were 4.6 (24 per 5,260 days) in the pre-change period and 7.4 (40 per 5,429 days) in the post-change period, a nonsignificant trend (P = 0.079). The incidence rate of CDAD for levofloxacin increased significantly from 3.9 (75 per 19,417 days) in the pre-change period to 10.7 (44 per 4,108 days) in the post-change period (P < 0.001). The incidence rates of CDAD in the post-change period did not differ significantly for ciprofloxacin, levofloxacin, and gatifloxacin (P = 0.119). There was an increase in the incidence of CDAD among all antibiotic users and fluoroquinolone users, but not among users of non-fluoroquinolone antibiotics, in the period following the formulary change from levofloxacin to gatifloxacin as the preferred fluoroquinolone. However, rates of CDAD among the 3 fluoroquinolone antibiotics in the post-change period were not significantly different, and levofloxacin was the only fluoroquinolone that was associated with a significant increase in the rate of CDAD between the pre-change and post-change periods. These findings suggest that the increase in the CDAD incidence rate was probably not attributable to the addition of gatifloxacin to the formulary.

Relationship between Antibiotic Exposure and Subsequent Clostridium Difficile-Associated Diarrhea

Objective The objective of this study was to assess the relationship between antibiotic exposure and subsequent Clostridium difficile-associated diarrhea (CDAD) in hospitalized patients. Methods A retrospective, case-control study with data collected between October 1, 2005 and March 31, 2006 was conducted. Cases consisted of patients with a documented new onset of diarrhea occurring a minimum of 72 hours following admission to the hospital and accompanied by a positive C. difficile toxin A and B enzyme immunoassay. Two controls were matched to each case according to known risk factors for CDAD other than antibiotic use. A complete assessment of antibiotic use was made, including all regimens the patient received during the previous 8 weeks. The difference in antibiotic use in cases and controls was tested using the chi-square test. The association between specific antibiotic classes and subsequent CDAD was evaluated with an odds ratio. Results Prior antibiotic exposure was observed more frequently in these cases than in controls ( P = 0.035). Specifically, third-generation cephalosporins were found to be significantly associated with CDAD (odds ratio, 4.64; 95% confidence interval, 1.64 to 13.14). Conclusion This study showed that prior antibiotic exposure is associated with increased incidence of subsequent CDAD. Specifically, third-generation cephalosporins were statistically associated with CDAD. Although results did not reach statistical significance, this study suggests that potential associations may exist between CDAD and prior exposure to antipseudomonal penicillins, cefepime, carbapenems, fluoroquinolones, and intravenous vancomycin.