Arjun Gupta

Community-acquired Clostridium difficile infection: an increasing public health threat.

There has been a startling shift in the epidemiology of Clostridium difficile infection over the last decade worldwide, and it is now increasingly recognized as a cause of diarrhea in the community. Classically considered a hospital-acquired infection, it has now emerged in populations previously considered to be low-risk and lacking the traditional risk factors for C. difficile infection, such as increased age, hospitalization, and antibiotic exposure. Recent studies have demonstrated great genetic diversity for C. difficile, pointing toward diverse sources and a fluid genome. Environmental sources like food, water, and animals may play an important role in these infections, apart from the role symptomatic patients and asymptomatic carriers play in spore dispersal. Prospective strain typing using highly discriminatory techniques is a possible way to explore the suspected diverse sources of C. difficile infection in the community. Patients with community-acquired C. difficile infection do not necessarily have a good outcome and clinicians should be aware of factors that predict worse outcomes in order to prevent them. This article summarizes the emerging epidemiology, risk factors, and outcomes for community-acquired C. difficile infection.

Association of Gastric Acid Suppression With Recurrent Clostridium difficile Infection: A Systematic Review and Meta-analysis

Importance Gastric acid suppression has been associated with an increased risk of primary Clostridium difficile infection (CDI), but the risk of recurrent CDI in patients taking gastric acid suppressant medications is unclear. Objective To perform a systematic review and meta-analysis to evaluate the association between gastric acid suppressants and recurrent CDI. Data Sources MEDLINE, EMBASE, the Cochrane Central Register, the Cochrane Database, and Web of Science were searched from January 1, 1995, to September 30, 2015, for studies assessing the association between gastric acid suppressant exposure and recurrent CDI. Search terms included Clostridium difficile, pseudomembranous colitis, proton pump inhibitor, and histamine H2 blocker. Study Selection Case-control studies, cohort studies, and clinical trials that included patients with CDI who did or did not receive gastric acid suppressant therapy and who were evaluated for recurrent CDI were included, with no restriction on study setting (inpatient or outpatient). Data Extraction and Synthesis The Newcastle-Ottawa scale was used to assess the methodologic quality of included studies. In this scale, case-control and cohort studies were scored on selection, comparability, and ascertainment of the outcome of interest. Data were independently abstracted to a predetermined collection form by 2 investigators. Summary odds ratio estimates with 95% CIs were calculated using the random-effects model and software to calculate the pooled effect size of studies reporting multivariate analyses. Main Outcomes and Measures Risk of recurrent infection in patients with CDI and its association with use of gastric acid suppressant medication. Results Sixteen observational studies were included, together reporting 7703 patients with CDI; among these, 1525 patients (19.8%) developed recurrent CDI. The rate of recurrent CDI in patients with gastric acid suppression was 22.1% (892 of 4038 patients) compared with 17.3% (633 of 3665) in patients without gastric acid suppression, which indicated an increased risk by meta-analysis (odds ratio [OR], 1.52; 95% CI, 1.20-1.94; P < .001). There was significant heterogeneity among the studies, with an I2 value of 64%. Subgroup analyses of studies adjusting for age and potential confounders confirmed an increased risk of recurrent CDI with use of gastric acid suppressants (OR, 1.38; 95% CI, 1.08-1.76; P = .02). Conclusions and Relevance Meta-analyses of observational studies suggest that patients who receive gastric acid suppressants may be at increased risk for recurrent CDI. These data should be interpreted with caution because they may be confounded owing to the observational design of the individual studies. It may be reasonable to re-evaluate the need for these medications in patients with CDI.

Endoscopically inserted nasobiliary catheters for high dose-rate brachytherapy as part of neoadjuvant therapy for perihilar cholangiocarcinoma.

BACKGROUND AND AIM Selected patients with unresectable perihilar cholangiocarcinoma can undergo neoadjuvant chemoradiotherapy followed by liver transplantation, which has been shown to improve survival. The aim of this study was to determine the feasibility and safety of endoscopic transpapillary insertion of nasobiliary tubes (NBTs) and brachytherapy catheters for high dose-rate (HDR) brachytherapy as part of this neoadjuvant chemoradiotherapy. PATIENTS AND METHODS Medical records of patients undergoing biliary brachytherapy for hilar cholangiocarcinoma at the Mayo Clinic, Rochester were reviewed. Patients were treated with curative intent using external beam radiotherapy (4500 cGy), chemotherapy (5-FU or capecitabine), and HDR brachytherapy (930 - 1600 cGy in one to four fractions delivered over 1 - 2 days) prior to planned liver transplantation. RESULTS Between 2009 and 2013, 40 patients underwent biliary HDR brachytherapy via endoscopically placed NBTs (8.5 - 10 Fr). Patients had a median age of 55 years (range 28 - 68); 25 patients (62.5 %) had primary sclerosing cholangitis. Prior to therapy, 29 patients (72.5 %) had plastic stents, two (5 %) had metal stents, and nine (22.5 %) had no stents. Bilateral NBTs were placed in five patients (12.5 %). NBT/brachytherapy catheter displacement was seen in eight patients (20 %) - five intraprocedure and three post-procedure. A radiotherapy error and NBT kinking each occurred once. Post-procedure adverse events included: cholangitis (n = 5; 12.5 %), severe abdominal pain (n = 3; 7.5 %), duodenopathy (n = 3; 7.5 %), gastropathy (n = 3; 7.5 %), and both duodenopathy and gastropathy (n = 2; 5 %). CONCLUSION HDR biliary brachytherapy administered via endoscopically placed NBTs and brachytherapy catheters is technically feasible and appears reasonably safe in selected patients with unresectable perihilar cholangiocarcinoma.

Extraintestinal Clostridium difficile Infections: A Single-Center Experience

OBJECTIVES To evaluate the clinical burden of extraintestinal Clostridium difficile infection (CDI) seen at a single institution and to characterize the management and outcomes of these rare infections. PATIENTS AND METHODS A retrospective medical record review was conducted to identify patients with isolation of C difficile from extraintestinal sites from January 1, 2004, through December 31, 2013. Medical records were reviewed and data, including demographic characteristics, microbiology, clinical associations, management, and infection outcomes, were abstracted. RESULTS Overall, 40 patients with extraintestinal CDI were identified: 25 had abdominopelvic infections, 11 had bloodstream infections, 3 had wound infections, and 1 had pulmonary infection. C difficile was isolated with other organisms in 63% of cases. A total of 85% of infections were nosocomial. Factors associated with extraintestinal CDI included surgical manipulation of the gastrointestinal tract (88%), recent antibiotic exposure (88%), malignant tumors (50%), and proton pump inhibitor use (50%). Diarrhea was present in 18 patients (45%), 12 of whom had C difficile polymerase chain reaction (PCR)-positive stool samples. All isolates tested were susceptible to metronidazole and piperacillin-tazobactam. Management included both antimicrobial therapy and guided drainage or surgical intervention in all but one patient. The infection-associated mortality rate was 25%, with death a median of 16 days (range, 1-61 days) after isolation of C difficile. CONCLUSION Extraintestinal CDI is uncommon and often occurs in patients with surgical manipulation of the gastrointestinal tract and well-recognized risk factors for intestinal CDI. Management of extraintestinal CDI includes both antimicrobial and surgical therapies. Extraintestinal CDI is characterized by poor outcome with high mortality.

Outcomes in children with Clostridium difficile infection: results from a nationwide survey

Objective: Hospital- and population-based studies demonstrate an increasing incidence of Clostridium difficile infection (CDI) in adults and children; although pediatric CDI outcomes are incompletely understood. We analysed United States National Hospital Discharge Survey (NHDS) data to study CDI in hospitalized children. Methods: NHDS data for 2005–2009 (demographics, diagnoses and discharge status) were obtained; cases and comorbidities were identified using ICD-9 codes. Weighted univariate and multivariate analyses were performed to ascertain incidence of CDI; associations between CDI and outcomes [length of stay (LOS), colectomy, all-cause in-hospital mortality and discharge to a care facility (DTCF)]. Results: Of an estimated 13.8 million pediatric inpatients; 46 176 had CDI; median age was 3 years; overall incidence was 33.5/10 000 hospitalizations. The annual frequency of CDI did not vary from 2005 to 2009 (0.24–0.43%; P = 0.64). On univariate analyses, children with CDI had a longer median LOS (6 vs 2 days), higher rates of colectomy [odds ratio (OR) 2.0; 95% confidence interval (CI) 1.7–2.4], mortality (OR 2.5; 95% CI 2.3–2.7), and DTCF (OR 1.6; 95% CI 1.6–1.7) (all P < 0.0001). After adjusting for age, sex and comorbidities, CDI was an independent and the strongest predictor of increased LOS (adjusted mean difference, 6.4 days; 95% CI 5.4–7.4), higher rates of colectomy (OR 2.1; 95% CI 1.8–2.5), mortality (OR 2.3; 95% CI 2.2–2.5), and DTCF (OR 1.7; 95% CI 1.6–1.8) (all P < 0.0001). On excluding infants from the analysis, children with CDI had higher rates of mortality, DTCF and longer LOS than children without CDI. Conclusions: Despite increased awareness and advancements in management, CDI remains a significant problem and is associated with increased LOS, colectomy, in-hospital mortality and DTCF in hospitalized children.