Chaitanya Pant

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.

Association of Clostridium difficile infection with outcomes of hospitalized solid organ transplant recipients: Results from the 2009 Nationwide Inpatient Sample database

Diarrhea is a frequent and potentially severe complication in solid organ transplant (SOT) recipients. One of the most common infectious etiologies of diarrhea in these patients is Clostridium difficile. Our objective was to investigate the association of C. difficile infection (CDI) with the outcomes of hospitalized SOT patients.

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.

Epidemiology of acute pancreatitis in hospitalized children in the United States from 2000-2009.

Background Single-center studies suggest an increasing incidence of acute pancreatitis (AP) in children. Our specific aims were to (i) estimate the recent secular trends, (ii) assess the disease burden, and (iii) define the demographics and comorbid conditions of AP in hospitalized children within the United States. Methods We used the Healthcare Cost and Utilization Project Kids’ Inpatient Database, Agency for Healthcare Research and Quality for the years 2000 to 2009. Extracted data were weighted to generate national-level estimates. We used the Cochrane-Armitage test to analyze trends; cohort-matching to evaluate the association of AP and in-hospital mortality, length of stay, and charges; and multivariable logistic regression to test the association of AP and demographics and comorbid conditions. Results We identified 55,012 cases of AP in hospitalized children (1–20 years of age). The incidence of AP increased from 23.1 to 34.9 (cases per 10,000 hospitalizations per year; P<0.001) and for all-diagnoses 38.7 to 61.1 (P<0.001). There was an increasing trend in the incidence of both primary and all-diagnoses of AP (P<0.001). In-hospital mortality decreased (13.1 to 7.6 per 1,000 cases, P<0.001), median length of stay decreased (5 to 4 days, P<0.001), and median charges increased (

Clostridium difficile infection in the hospitalized pediatric population increasing trend in disease incidence

14,956 to

Clostridium difficile infection in children: A comprehensive review

22,663, P<0.001). Children with AP compared to those without the disease had lower in-hospital mortality (adjusted odds ratio, aOR 0.86, 95% CI, 0.78–0.95), longer lengths of stay (aOR 2.42, 95% CI, 2.40–2.46), and higher charges (aOR 1.62, 95% CI, 1.59–1.65). AP was more likely to occur in children older than 5 years of age (aORs 2.81 to 5.25 for each 5-year age interval). Hepatobiliary disease was the comorbid condition with the greatest association with AP. Conclusions These results demonstrate a rising incidence of AP in hospitalized children. Despite improvements in mortality and length of stay, hospitalized children with AP have significant morbidity.