David D.K. Rolston

Community-associated Clostridium difficile infection and antibiotics: a meta-analysis

OBJECTIVES Antibiotic exposure is the most important risk factor for Clostridium difficile infection (CDI). Most evaluations of antimicrobial risk factors have been conducted in healthcare settings. The objective of this meta-analysis was to evaluate the association between antibiotic exposure and community-associated CDI (CA-CDI) (i.e. symptom onset in the community with no healthcare facility admission within 12 weeks) and to determine the classes of antibiotics posing the greatest risk. METHODS We searched four electronic databases for subject headings and text words related to CA-CDI and antibiotics. Studies that investigated the risk of CA-CDI associated with antibiotic usage were considered eligible. Data from the identified studies were combined using a random-effects model and ORs were calculated. RESULTS Of 910 citations identified, eight studies (n = 30 184 patients) met our inclusion criteria. Antibiotic exposure was associated with an increased risk of CA-CDI (OR 6.91, 95% CI 4.17-11.44, I(2) = 95%). The risk was greatest with clindamycin (OR 20.43, 95% CI 8.50-49.09) followed by fluoroquinolones (OR 5.65, 95% CI 4.38-7.28), cephalosporins (OR 4.47, 95% CI 1.60-12.50), penicillins (OR 3.25, 95% CI 1.89-5.57), macrolides (OR 2.55, 95% CI 1.91-3.39) and sulphonamides/trimethoprim (OR 1.84, 95% CI 1.48-2.29). Tetracyclines were not associated with an increased CDI risk (OR 0.91, 95% CI 0.57-1.45). CONCLUSIONS Antibiotic exposure was an important risk factor for CA-CDI, but the risk was different amongst different antibiotic classes. The risk was greatest with clindamycin followed by fluoroquinolones and cephalosporins, whereas tetracyclines were not associated with an increased risk.

Association Between Proton Pump Inhibitor Therapy and Clostridium difficile Infection in a Meta-Analysis

BACKGROUND & AIMS In the past decade, there has been a growing epidemic of Clostridium difficile infection (CDI). During this time, use of proton pump inhibitors (PPIs) has increased exponentially. We evaluated the association between PPI therapy and the risk of CDI by performing a meta-analysis. METHODS We searched MEDLINE and 4 other databases for subject headings and text words related to CDI and PPI in articles published from 1990 to 2010. All observational studies that investigated the risk of CDI associated with PPI therapy and used CDI as an end point were considered eligible. Two investigators screened articles independently for inclusion criteria, data extraction, and quality assessment; disagreements were resolved based on consensus with a third investigator. Data were combined by means of a random-effects model and odds ratios were calculated. Subgroup and sensitivity analyses were performed based on study design and antibiotic use. RESULTS Thirty studies (25 case-control and 5 cohort) reported in 29 articles met the inclusion criteria (n = 202,965). PPI therapy increased the risk for CDI (odds ratio, 2.15, 95% confidence interval, 1.81-2.55), but there was significant heterogeneity in results among studies (P < .00001). This association remained after subgroup and sensitivity analyses, although significant heterogeneity persisted among studies. CONCLUSIONS PPI therapy is associated with a 2-fold increase in risk for CDI. Because of the observational nature of the analyzed studies, we were not able to study the causes of this association. Further studies are needed to determine the mechanisms by which PPI therapy might increase risk for CDI.

Diagnostic Accuracy of Real-time Polymerase Chain Reaction in Detection of Clostridium difficile in the Stool Samples of Patients With Suspected Clostridium difficile Infection: A Meta-Analysis

BACKGROUND Current detection methods for Clostridium difficile infection (CDI) can be time-consuming and have variable sensitivities. Real-time polymerase chain reaction (PCR) may allow earlier and more accurate diagnosis of CDI than other currently available diagnostic tests. A meta-analysis was performed to determine the diagnostic accuracy of real-time PCR. METHODS We searched MEDLINE (Pubmed/Ovid) and 4 other online electronic databases (1995-2010) to identify diagnostic accuracy studies that compared PCR with cell culture cytotoxicity neutralization assay (CCCNA) or anaerobic toxigenic culture (TC) of C. difficile. Screening for inclusion, data extraction, and quality assessment were carried out independently by 2 investigators and disagreements resolved. Data were combined by means of a random-effects model, and summary receiver operating characteristic curves and diagnostic odds ratios were calculated. RESULTS Nineteen studies (7392 samples) met our inclusion criteria. The overall mean sensitivity of PCR was 90% (95% confidence interval [CI]: 88%-91%), specificity 96% (CI: 96%-97%), positive likelihood ratio 26.89 (CI: 20.81-34.74), negative likelihood ratio 0.11 (CI: .08-.15), diagnostic odds ratio 278.23 (CI: 213.56-362.50), and area under the curve 0.98 (CI: .98-.99). Test accuracy depended on the prevalence of C. difficile but not on the reference test used. At C. difficile prevalence of <10%, 10%-20% and >20% the positive predictive value and the negative predictive value were 71%, 79%, 93% and 99%, 98% and 96%, respectively. CONCLUSIONS Real-time PCR has a high sensitivity and specificity to confirm CDI. Overall diagnostic accuracy is variable and depends on CDI prevalence.

Acid‐suppressive therapy is associated with spontaneous bacterial peritonitis in cirrhotic patients: A meta‐analysis

Proton pump inhibitors (PPI) and H2‐receptor antagonists (H2RA) are frequently prescribed in hospitalized patients with cirrhosis. There are conflicting reports regarding the role of acid‐suppressive therapy in predisposing hospitalized patients with cirrhosis to spontaneous bacterial peritonitis (SBP). The aim of this meta‐analysis was to evaluate the association between acid‐suppressive therapy and the risk of SBP in hospitalized patients with cirrhosis.

Do fluoroquinolones predispose patients to Clostridium difficile associated disease? A review of the evidence

ABSTRACT Background: Clostridium difficile associated diarrhea (CDAD) is an important cause of hospital-acquired diarrhea, and increasingly of community-acquired diarrhea. The occurrence of CDAD in the hospitalized patient is associated with increased length of stay, morbidity, mortality, and healthcare costs. Exposure to antimicrobials is the single most important predisposing factor for acquiring CDAD. The data suggesting that fluoroquinolones are an important risk factor for CDAD is becoming stronger. Also, different fluoroquinolones may pose different risks for CDAD development. Objectives: The aim of this commentary is to summarize the literature as it relates to the role that fluoroquinolones may have in CDAD. Methods: PubMed and Ovid MEDLINE were searched using the terms fluoroquinolones, ciprofloxacin, levofloxacin, gatifloxacin, and moxifloxacin in combination with C. difficile, CDAD, pseudomembranous colitis and antibiotic associated diarrhea. Results: The evidence for an association between fluoroquinolone use and CDAD, especially CDAD due to the hypervirulent NAP1 strain or the polymerase chain reaction ribotype 027, is becoming stronger. Conclusions: Fluoroquinolones appear to predispose patients to CDAD. The data are suggestive but not conclusive. More studies are needed to define the role that fluoroquinolones play in the development of CDAD. Meticulous and enhanced infection control practices at all times and the judicious use of antimicrobials will help contain the epidemic of CDAD.

Risk Factors for Recurrent Clostridium difficile Infection: A Systematic Review and Meta-Analysis

OBJECTIVE An estimated 20-30% of patients with primary Clostridium difficile infection (CDI) develop recurrent CDI (rCDI) within 2 weeks of completion of therapy. While the actual mechanism of recurrence remains unknown, a variety of risk factors have been suggested and studied. The aim of this systematic review and meta-analysis was to evaluate current evidence on the risk factors for rCDI. DESIGN We searched MEDLINE and 5 other databases for subject headings and text related to rCDI. All studies investigating risk factors of rCDI in a multivariate model were eligible. Information on study design, patient population, and assessed risk factors were collected. Data were combined using a random-effects model and pooled relative risk ratios (RRs) were calculated. RESULTS A total of 33 studies (n=18,530) met the inclusion criteria. The most frequent independent risk factors associated with rCDI were age≥65 years (risk ratio [RR], 1.63; 95% confidence interval [CI], 1.24-2.14; P=.0005), additional antibiotics during follow-up (RR, 1.76; 95% CI, 1.52-2.05; P<.00001), use of proton-pump inhibitors (PPIs) (RR, 1.58; 95% CI, 1.13-2.21; P=.008), and renal insufficiency (RR, 1.59; 95% CI, 1.14-2.23; P=.007). The risk was also greater in patients previously on fluoroquinolones (RR, 1.42; 95% CI, 1.28-1.57; P<.00001). CONCLUSIONS Multiple risk factors are associated with the development of rCDI. Identification of modifiable risk factors and judicious use of antibiotics and PPI can play an important role in the prevention of rCDI.

Risk of colorectal cancer in ulcerative colitis in India

Background:  The risk for colorectal cancer (CRC) in ulcerative colitis (UC) in India is not known.

Repeat Stool Testing to Diagnose Clostridium difficile Infection Using Enzyme Immunoassay Does Not Increase Diagnostic Yield

BACKGROUND & AIMS Clostridium difficile infection (CDI) is a hospital-acquired infection with increasing incidence and severity. The most frequently used test to diagnose CDI is an enzyme immunoassay (EIA) for toxins A and B in stool samples. It is common to test 2 or more stool samples, based on the assumption that this detects CDI with greater sensitivity than analysis of 1 sample. We investigated whether repeat stool testing significantly improves the diagnostic yield for CDI. METHODS We performed a retrospective analysis of hospitalized patients who were tested for CDI using EIA. From year 2005 to 2008, 39,402 stool samples from 17,971 patients with 29,373 diarrhea episodes were tested. Transition probabilities were calculated based on results from repeated tests. RESULTS A total of 2692 diarrheal episodes (9.17%) were diagnosed with CDI. Based on results of 3 consecutive tests, 2675 (99.36%) were diagnosed with CDI. The first stool sample tested produced positive results for 90.7% of cases. When samples were tested consecutively, for the second and third time, an additional 6.6% and 2% patients had positive test results, respectively. If the first test result was negative, the probability of the second test result being positive was 2.7%. If the first 2 test results were negative, the probability of the third test result being positive was 2.3%. CONCLUSIONS In patients who had multiple stool samples tested for CDI by EIA, almost 91% were accurately diagnosed based on the results of a single stool sample alone. Subsequent testing yielded a positive result in only 8.6% of patients. We therefore recommend that repeat testing not be done on a routine basis because it does not significantly improve diagnostic yield.

Repeat stool testing for Clostridium difficile using enzyme immunoassay in patients with inflammatory bowel disease increases diagnostic yield

Abstract Background: The incidence and severity of Clostridium difficile infection (CDI) in patients with inflammatory bowel disease (IBD) is increasing. CDI is diagnosed by toxin enzyme immunoassay (EIA) or real-time polymerase chain reaction (PCR) performed on stool samples. An earlier study evaluating EIA in IBD patients with CDI suggested that more than one stool sample be tested to increase diagnostic yield. We investigated whether repeat stool testing improves diagnostic accuracy for CDI in hospitalized IBD patients compared to hospitalized patients with CDI and no IBD. Methods: We performed retrospective data analysis from January 2005–May 2011 on 63,086 hospitalized patients who were tested for CDI using EIA or PCR. Of these, 2579 patients had IBD. Transition probabilities were calculated based on results from repeated tests. Results: Inclusive of all inpatients tested for CDI, 56,583 were tested using toxin EIA and 6503 were tested using PCR. In patients with no IBD, the first stool sample tested was positive in 90% and 94% with EIA and PCR respectively. In IBD patients tested using EIA, 101 were diagnosed with CDI. The first stool sample tested was positive in 81% of patients. Successive second and third stool samples yielded additional 14% and 5% CDI positive IBD patients. Conclusions: Approximately one in five IBD patients with CDI required repeat testing to yield a positive result with EIA. There are minimal diagnostic gains of repeat testing by EIA or PCR in patients without IBD. We recommend repeat stool testing for CDI when using EIA to increase diagnostic yield in IBD patients.

All-Cause and Specific-Cause Mortality Risk After Roux-en-Y Gastric Bypass in Patients With and Without Diabetes

OBJECTIVE This study assessed all-cause and specific-cause mortality after Roux-en-Y gastric bypass (RYGB) and in matched control subjects, stratified by diabetes status. RESEARCH DESIGN AND METHODS RYGB patients were matched by age, BMI, sex, and diabetes status at time of surgery to nonsurgical control subjects using data from the electronic health record. Kaplan-Meier curves and Cox regression were used to assess differences in all-cause and specific-cause mortality between RYGB patients and control subjects with and without diabetes. RESULTS Of the 3,242 eligible RYGB patients enrolled from January 2004 to December 2015, control subjects were identified for 2,428 (n = 625 with diabetes and n = 1,803 without diabetes). Median postoperative follow-up was 5.8 years for patients with diabetes and 6.7 years for patients without diabetes. All-cause mortality was reduced in RYGB patients compared with control subjects only for those with diabetes at the time of surgery (adjusted hazard ratio 0.44; P < 0.0001). Mortality was not significantly improved in RYGB patients without diabetes compared with control subjects without diabetes (adjusted hazard ratio 0.84; P = 0.37). Deaths from cardiovascular diseases (P = 0.011), respiratory conditions (P = 0.017), and diabetes P = 0.011) were more frequent in control subjects with diabetes than in RYGB patients with diabetes. RYGB patients without diabetes were less likely to die of cancer (P = 0.0038) and respiratory diseases (P = 0.046) than control subjects without diabetes but were at higher risk of death from external causes (P = 0.012), including intentional self-harm (P = 0.025), than control subjects without diabetes. CONCLUSIONS All-cause mortality benefits of RYGB are driven predominantly by patients with diabetes at the time of surgery. RYGB patients with diabetes were less likely to die of cardiovascular diseases, diabetes, and respiratory conditions than their counterparts without RYGB.