Clostridium Difficile-associated Disease Research Articles

Antimicrobial de‐escalation strategies in hospitalized patients with pneumonia, intra‐abdominal infections, and bacteremia

AbstractIncreasing numbers of serious hospital/healthcare‐ or community‐acquired infections are caused by resistant (often multi‐drug resistant) bacterial pathogens. Because delayed or ineffective initial therapy can have severe negative consequences, patients at risk for these types of infections typically receive initial empiric antibiotic therapy with a broad‐spectrum regimen covering the most likely pathogens, based on local surveillance data and risk factors for infection with a resistant microorganism. While improving the likelihood of a successful outcome, use of broad‐spectrum, often high‐dose, empiric antimicrobial therapy also creates pressure for the selection or development of resistant microorganisms, as well as increasing costs and possibly exposing patients to adverse events or collateral damage such as Clostridium difficile‐associated disease. De‐escalation is a strategy that attempts to balance the competing aims of providing initial empiric therapy that is appropriate and covers the likely pathogens, and limiting antimicrobial exposure and increased risk for emergence of resistant pathogens. More specifically, the de‐escalation strategy involves collection of cultures for later microbiological assessment before initiating broad‐spectrum empiric therapy covering the most likely pathogens, with the intention of streamlining or de‐escalating to a more narrow‐spectrum antimicrobial regimen 2–3 days later if warranted by clinical status and culture results. In some cases, negative culture results and subsequent clinical review may allow for termination of initial empiric therapy. In this manner, de‐escalation enables more effective targeting of the causative pathogen(s), elimination of redundant therapy, a decrease in antimicrobial pressure for emergence of resistance, and cost savings. This article examines application of the de‐escalation strategy to 3 case patients, one with healthcare‐associated pneumonia, another with complicated intra‐abdominal infection, and a third with central line‐associated bacteremia. Journal of Hospital Medicine 2012;7:S13–S21. © 2012 Society of Hospital Medicine

Effect of cohorting strategy and focused care on incidence and mortality of C difficile associated diarrhea: preliminary results from an observational study: Category: Clinical lesson

Clostridium Difficile is a common bacteria carried by 8% population. In CDAD (Clostridium Difficile Associated Disease) symptoms arise as a result of disruption of the microflora in the bowel. The primary methods for this include use of antibiotics, and faeco-oral contamination. Both these methods serve to favour proliferation of Clostridium Difficile. Symptoms include diarrhoea, circulatory collapse, pseudomembranous colitis and toxic megacolon, all in turn potentially leading to septicaemia and perforation. A review of CDAD mortality in Midstaffordshire NHS Trust in 2008 identified measures for improvement of the management of CDAD. In January 2009 new antimicrobial guidelines and environmental hygiene changes were introduced. In March 2009 a new treatment protocol for managing CDAD was implememted, including appropriate initiation of antibiotics, attention to nutrition and prompt escalation of treatment and in August 2009 the CDAD cohort ward was completed.

Evaluation of the impact of “ The Clostridium difficile review group” on Clostridium difficile associated disease (CDAD) within an acute NHS hospital Trust: Category: Lesson in Microbiology & Infection Control

Evaluation of the impact of “ The Clostridium difficile review group” on Clostridium difficile associated disease (CDAD) within an acute NHS hospital Trust: Category: Lesson in Microbiology & Infection Control

Toxin assay is more reliable than ICD‐9 data and less time‐consuming than chart review for public reporting of Clostridium difficile hospital case rates

Clostridium difficile-associated disease (CDAD) is common and has a 6.1% mortality. Governmental agencies have recommended surveillance, but reporting increases health care costs. We sought to identify a reliable method of reporting CDAD that will not significantly increase health care costs. Patients were identified via database query for International Statistical Classification of Diseases and Related Health Problems, 9th Edition (ICD-9) codes and C. difficile toxin positivity. All identified patients underwent a chart review, which was used to determine the accuracy of the database query methods. Methods of determining whether CDAD was acquired at the reporting institution were studied, and time required to perform each method was measured. The toxin assay reported 96.1% (369/384) of cases and had a positive predictive value of 100%. No difference was found in comparison of the toxin assay case rate of 15.7 per 1000 discharged patients to the rate of 16.3 identified by chart review (P = 0.440; 95% confidence interval [CI], 14.1-17.4), whereas the ICD-9 method was found to be significantly different by reporting 116.1% (446/384) of cases for a case rate of 19.0 per 1000 discharges (P = 0.001; 95% CI, 17.3-20.8). The time for data extraction via the toxin assay method required only 842 minutes, while the chart review method consumed 21,899 minutes. A positive C. difficile toxin assay accurately reports the institutional incidence of disease and is more reliable than ICD-9 query. This process can be instituted at a fraction of the cost of the standard chart review, and enables governmental agencies to inexpensively add CDAD to their list of reportable diseases.

Over-Prescription of Acid-Suppressing Medications in Infants: How It Came About, Why It’s Wrong, and What to Do About It

It has been almost 20 years since proton pump inhibitors (PPIs) were initially shown to be effective, safe, and well-tolerated for the short-term treatment of gastroesophageal reflux disease (GERD) in children over 1 year of age 1 ; GERD diagnosed on the basis of symptoms and hard diagnostic evidence of erosive esophagitis seen at endoscopy. 2 In these studies, mostly performed in children 2 to 17 years of age, 1-3 PPIs were shown to effectively treat symptoms and erosive esophagitis that were refractory to histamine-2receptor antagonists (H2RA), buffering agents, prokinetics, and in some subjects, antireflux surgery. Subsequent to those studies with omeprazole, other PPIs were found to be similarly effective. 4-8 Efficacy and safety were also shown for maintenance of remission of chronic, relapsing erosive esophagitis in prospective studies as long as 2 years, 9 and retrospective studies as long as 11 years of use. 10 Approximately 80% 10 of children who require long-term treatment for GERD have underlying disorders that predispose them to GERD, such as neurologic impairment, repaired congenital esophageal anomalies (eg, esophageal atresia), chronic lung disease, hiatal hernia, a strong family history of GERD, Barrett’s esophagus, or esophageal adenocarcinoma, or obesity. 11 In children without these underlying disorders, GERDisusuallynotchronicorsevere, 12 andmostcommonly follows a presumed upper gastrointestinal infection with post-infectious dysmotility and delayed gastric emptying, which resolves with time. In other words, in most otherwise healthy children, GERD is not chronic. In children in whom it is, the use of PPIs has revolutionized the long-term treatment of GERD, much for the better, including allowing for significantly decreased rates of antireflux surgery in some centers. 13 In this overall context, the topic of reflux in infants (ie, 7-fold increase in PPI prescription. One of the PPIs, available in a child-friendly liquid formulation, saw a 16-fold increase in use during that 6-year period. 14 Overall, approximately 0.5% of the approximately one million infants in the study database received a PPI during their first year of life. Approximately 50% of the infants started taking a PPI before 4 months of age. 15 These data would imply that somehow the diagnosis of GERD has been missed over the past several decades or has recently become a major scourge of infants in the developed world, with acid suppressing drugs becoming a new essential food group in their own right. This change in practice has come about for several reasons, none based in medical science. There is, however, data to show that this practice does not serve our patients. Two phenomena have long been observed in otherwise healthy, thriving infants. First, many of them spit up on a daily basis—some 40% to 70%. 16,17 The developing, rapidly-growing infant takes in feeding volumes that on a per-kg basis are huge compared with older children or adults. Infants have relatively poor gastric compliance and a short esophagus; therefore, some of the large volume intake simply overflows upward, or sometimes ‘‘spills’’ (lingua Australiana) out through the mouth. This has long been recognized as physiologic reflux not reflux disease [ie, not GERD]), and it is self-resolving in approximately 95% of

Diverting Loop Ileostomy and Colonic Lavage

To determine whether a minimally invasive, colon-preserving approach could serve as an alternative to total colectomy in the treatment of severe, complicated Clostridium difficile-associated disease (CDAD). C. difficile is a significant cause of morbidity and mortality worldwide. Most cases will respond to antibiotic therapy, but 3% to 10% of patients progress to a severe, complicated, or "fulminant" state of life-threatening systemic toxicity. Although the advocated surgical treatment of total abdominal colectomy with end ileostomy improves survival in severe, complicated CDAD, outcomes remain poor with associated mortality rates ranging from 35% to 80%. All patients who were diagnosed with severe, complicated ("fulminant") CDAD and were treated at the University of Pittsburgh Medical Center or VA Pittsburgh Healthcare System between June 2009 and January 2011 were treated with this novel approach. The surgical approach involved creation of a loop ileostomy, intraoperative colonic lavage with warmed polyethylene glycol 3350/electrolyte solution via the ileostomy and postoperative antegrade instillation of vancomycin flushes via the ileostomy. The primary end point for the study was resolution of CDAD. The matching number of patients treated with colectomy for CDAD preceding the initiation of this current treatment strategy was analyzed for historical comparison. Forty-two patients were treated during this time period. There was no significant difference in age, sex, pharmacologic immunosuppression, and Acute Physiology and Chronic Health Evaluation-II scores between our current cohort and historical controls. The operation was accomplished laparoscopically in 35 patients (83%). This treatment strategy resulted in reduced mortality compared to our historical population (19% vs 50%; odds ratio, 0.24; P = 0.006). Preservation of the colon was achieved in 39 of 42 patients (93%). Loop ileostomy and colonic lavage are an alternative to colectomy in the treatment of severe, complicated CDAD resulting in reduced morbidity and preservation of the colon.

Irish Dietitians' Opinions and Use of Probiotics in Patients With Clostridium difficile-associated Disease

*Department of Nutrition and Dietetics St Vincent's University Hospital, Dublin 4 †School of Biological Sciences, Dublin Institute of Technology, Dublin 8 Republic of Ireland The authors declare no conflict of interests or industry support for this work.

Impact of Clostridium difficile-associated disease in a regional hospital

For the recent years, our institution had an incidence of Clostridium difficile associated disease (CDAD) higher than the provincial rate. This study reviewed the burden of CDAD in our hospital.

Probiotics for prevention of antibiotic‐associated diarrhea and Clostridium difficile‐associated disease in hospitalized adults—A meta‐analysis

A serious complication associated with the use of most antibiotics is antibiotic-associated diarrhea (AAD). The purpose of this article is to report findings from a meta-analysis of available studies on adult hospitalized populations to evaluate efficacy of probiotics for prevention of AAD and Clostridium difficile-associated disease (CDAD). A comprehensive, systematic search was conducted to identify all relevant studies on probiotic efficacy for prevention of AAD and CDAD. Data synthesis was done using MAStARI software from the Joanna Briggs Institute (University of Adelaide, Australia). AAD affects one in five people on antibiotics. Risk factors for the development of AAD include the use of broad-spectrum antibiotics and host factors such as age, health status, hospitalization status, and exposure to nosocomial pathogens. About a third of AAD cases have CDAD. Meta-analysis showed that administration of probiotics led to a statistically significant relative risk reduction of 44% for AAD and 71% for CDAD. Extended hospital stays, readmissions, and higher hospital costs are just some of the consequences of ADD and CDAD. Strategies currently used include discontinuing or changing the inciting antibiotic, restricting high-risk antibiotics, and encouraging the use of antibiotics based on sensitivity reports. Healthcare spending, morbidity, and mortality can potentially be reduced considerably by reducing the occurrence of ADD and CDAD by administering prophylaxis with probiotics concurrently with antibiotics.

Medication Exposures Associated With Increased Short-Term Mortality of Patients With Clostridium difficile- Associated Disease (CDAD)

Medication Exposures Associated With Increased Short-Term Mortality of Patients With Clostridium difficile- Associated Disease (CDAD)

A Prediction Model of Disease Severity in Clostridium difficile-Associated Disease

rence. Methods: Adults with CDI symptoms and a positive toxin test received oral fidaxomicin or vancomycin for ten days as part of a phase 3 clinical trial. Recurrence was defined as the reappearance of diarrhea and a positive stool toxin test within 4 weeks following completion of therapy. Multivariate analysis was used to identify patient characteristics at either the beginning or completion of therapy that correlated with recurrence or time to recurrence. Results: Of 518 patients (253 treatedwith fidaxomicin and 265with vancomycin), 106 had a recurrence of CDI (20.5%). The distribution of recurrences over timewas consistent with two distinct periods: early (within the first 2 weeks after stopping initial therapy; 10.5 reoccurrences/1000 patient days) and late (2 to 4 weeks after stopping initial therapy; 5.0 reoccurrences/1000 patient days). The table summarizes patient characteristics associated with increased incidence of early or late recurrence. Treatment with fidaxomicin was associated with a lower rate of early recurrence (5.9 recurrences/1000 patient days) compared with vancomycin (15.1 recurrences/1000 patient days, p<0.001). There was no difference between treatments in the rate of recurrence during weeks 3 and 4 of follow-up. Conclusions: CDI treatment with fidaxomicin resulted in a lower rate of early recurrence (within 14 days of completing therapy) than vancomycin. This differential effect is likely due to a less deleterious effect of fidaxomicin on normal fecal microflora. Late recurrence is likely related to a new infection and is affected by patient-related factors, not initial treatment choices. Such factors may define a group at high risk of a new infection and could guide prevention measures and treatment choices.

Understanding Clostridium difficile-Associated Disease (CDAD) in Children at a Tertiary Care Children's Hospital: A 6 Year Retrospective Study

Understanding Clostridium difficile-Associated Disease (CDAD) in Children at a Tertiary Care Children's Hospital: A 6 Year Retrospective Study

Decline in Clostridium difficile-associated disease rates in Singapore public hospitals, 2006 to 2008

BackgroundClostridium difficile is the major cause of pseudomembranous colitis associated with antibiotic use, and the spread of the hypervirulent epidemic ribotype 027/NAP-1 strain across hospitals worldwide has re-focused attention on this nosocomial pathogen. The overall incidence and trend of C. difficile-associated disease (CDAD) in Singapore is unknown, and a surveillance program to determine these via formal laboratory-based reporting was established.FindingsLaboratory and pharmacy data were collated from one tertiary and two secondary hospitals on a quarterly basis between 2006 and 2008. All hospitals tested for C. difficile using Immunocard Toxins A&B (Meridian Bioscience Inc., Cincinnati, OH) during this period. Duplicate positive C. difficile results within a 14-day period were removed. The CDAD results were compared with trends in hospital-based prescription of major classes of antibiotics.Overall CDAD incidence-density decreased from 5.16 (95%CI: 4.73 - 5.62) cases per 10,000 inpatient-days in 2006 to 2.99 (95%CI: 2.67 to 3.33) cases per 10,000 inpatient-days in 2008 (p < 0.001), while overall rates for C. difficile testing increased significantly (p < 0.001) within the same period. These trends were mirrored at the individual hospital level. Evaluation of antibiotic prescription data at all hospitals showed increasing use of carbapenems and fluoroquinolones, while cephalosporin and clindamycin prescription remained stable.ConclusionsOur results demonstrate a real decline of CDAD rates in three large local hospitals. The cause is unclear and is not associated with improved infection control measures or reduction in antibiotic prescription. Lack of C. difficile stool cultures as part of routine testing precluded determination of the decline of a major clone as a potential explanation. For more accurate epidemiological trending of CDAD and early detection of epidemic clones, data collection will have to be expanded and resources set in place for reference laboratory culture and typing.

Drugs and Severity of an Emerging Disease— Clostridium difficile Associated Disease

Drugs and Severity of an Emerging Disease— Clostridium difficile Associated Disease

Antimicrobial stewardship for inpatient facilities

Antibiotic stewardship aims to improve patient care and reduce unwanted consequences of antimicrobial overuse or misuse, including lowered efficacy, emergence of antimicrobial resistance, development of secondary infections, adverse drug reactions, increased length of hospital stay, and additional healthcare costs. Recent guidelines make specific recommendations for the development of institutional programs to enhance antimicrobial stewardship. Optimally, such programs should be comprehensive, multidisciplinary, supported by hospital and medical staff leadership, and should employ evidence-based strategies that best fit local needs and resources. An infectious diseases physician and clinical pharmacist with infectious diseases training are recommended as core members of the multidisciplinary team, although a hospitalist with interest (and perhaps additional training) in antimicrobial therapy may be able to fill the void. Program directors and core members should be compensated for their time. Principal proactive strategies--with evidence supporting their consideration--include prospective audits, with intervention and feedback, formulary restriction, and preauthorization. Other strategies include persistent one-on-one education, guidelines adapted to local needs, and informatics to support clinical decision making. Intervention goals are to prevent unnecessary antimicrobial starts, to streamline or de-escalate therapy early in its course, and to convert from parenteral to oral therapy, optimize dosing, and ensure the appropriate length of therapy. Most community hospitals, if sufficiently resourced, should be able to implement a successful antimicrobial stewardship program. Evidence suggests that good antimicrobial stewardship can lead to less overall and inappropriate antimicrobial use, lower drug-related costs, reductions in Clostridium difficile-associated disease, and, in some studies, less emergence of antimicrobial resistance.

Statin Use Associated With a Decreased Length of Hospital Stay in Diabetic Patients With Clostridium difficile Infection

Clostridium difficile colitis has been gradually increasing in frequency in the United States, with worsening patient outcomes ( 1. Morris AM Jobe BA Stoney M Sheppard BC Deveney CW Deveney KE Clostridium difficile colitis: An increasingly aggressive iatrogenic disease?. Arch Surg. 2002; 137: 1096-1100 Crossref PubMed Google Scholar ). Diabetes mellitus has been shown to be a risk factor for C difficile colitis ( 2. Muto CA Pokrywka M Shutt K et al. A large outbreak of Clostridium difficile-associated disease with an unexpected proportion of deaths and colectomies at a teaching hospital following increased fluoroquinolone use. Infect Control Hosp Epidemiol. 2005; 26: 273-280 Crossref PubMed Scopus (549) Google Scholar ). We assessed factors associated with an increased length of hospital stay in diabetic patients with C difficile colitis.

Infection Probability Score: A predictor of Clostridium difficile–associated disease onset in patients with haematological malignancy

Purpose to assess the predictive power of three systems: Infection Probability Score, APACHE II and KARNOFSKY score for the onset of Clostridium difficile–associated disease ( CDAD) in hematology–oncology patients. Methods and sample A retrospective pilot surveillance survey was conducted in the hematology unit of a general hospital in Greece. Data were collected by using an anonymous standardised case-record form. The sample consisted of 102 hospitalized patients. Results The majority of the patients (33.3%) suffered from acute myeloid leukemia. The cumulative incidence of CDAD was 10.8% and the incidence rate of C difficile associated diarrhea was 5 per 1000 patient-days (14.2 per 1000 patient-days at risk). Patients with CDAD had twofold higher time of mean length of hospital stay compared with patients without CDAD (38.82 ± 23.88 vs 19.45 ± 14.56 days). Additionally patients with CDAD had received a greater number of different antibiotics compared to those without CDAD (5.18 ± 1.99 vs 2.54 ± 2.13), suffered from diabetes, from non Hodgkin’s lymphoma, had a statistically significant higher duration of neutropenia ≥3 days and had received antifungal treatment. The best cutoff value of IPS for the prediction of CDAD was 13 with a sensitivity of 45.5% and a specificity of 82.4%. Conclusions IPS is an early diagnostic test for CDAD detection.

&lt;i&gt;Clostridium difficile&lt;/i&gt;-Associated Disease: Impact of the Updated SHEA/IDSA Guidelines

Clostridium difficile-associated disease (CDAD) is an increasingly difficult condition to treat because of the emergence of antibiotic resistance and highly pathogenic strains of bacteria. These newly identified strains affect patients in every facet of health care, from individuals in the community to those in intensive care units and all points in between. Appropriate management regarding diagnosis, infection control, pharmacotherapy, and prevention is the key to good outcomes in all patient populations. Geriatric patients are particularly at risk of acquiring CDAD as a result of their gradually declining immune systems and increased exposure to health care facilities. Therefore, they merit a higher level of attention when CDAD is suspected. In an effort to identify the best practices, the Society for Healthcare Epidemiology of America in conjunction with the Infectious Diseases Society of America developed guidelines regarding the diagnosis and management of Clostridium-associated disease. By utilizing these guidelines to educate other health care practitioners and by considering the recommendations in their own practice, pharmacists can have a positive impact on every facet of CDAD prevention and management.

Comparative Metagenomic Study of Alterations to the Intestinal Microbiota and Risk of NosocomialClostridum difficile–Associated Disease

This study investigated the relationship between hospital exposures, intestinal microbiota, and subsequent risk of Clostridium difficile-associated disease (CDAD), with use of a nested case-control design. The study included 599 patients, hospitalized from September 2006 through May 2007 in Montreal, Quebec, from whom fecal samples were obtained within 72 h after admission; 25 developed CDAD, and 50 matched controls were selected for analysis. Nonsteroidal anti-inflammatory drugs and antibiotic use were associated with CDAD. Fecal specimens were evaluated by 16S ribosomal RNA microarray to characterize bacteria in the intestinal microbiota during the at-risk period. Probe intensities were higher for Firmicutes, Proteobacteria, and Actinobacteria in the patients with CDAD, compared with controls, whereas probe intensities for Bacteroidetes were lower. After epidemiologic factors were controlled for, only Bacteroidetes and Firmicutes remained significantly and independently associated with development of CDAD. Hospital exposures were associated with changes in the intestinal microbiota and risk of CDAD, and these changes were not driven exclusively by antimicrobial use.

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.