Robert Orenstein

Risk Factors for Opportunistic Infections in Patients With Inflammatory Bowel Disease

BACKGROUND & AIMS We sought to identify and quantify the clinical factors that were associated with opportunistic infections in inflammatory bowel disease patients. METHODS We identified 100 consecutive IBD patients with opportunistic infections. For each case, 2 matched IBD patients who did not have a history of opportunistic infection were selected as controls. Conditional logistic regression was used to assess associations between putative risk factors and opportunistic infections, presented as odds ratios (OR) and 95% confidence intervals (CIs). RESULTS In univariate analysis, use of corticosteroids (OR, 3.4; 95% CI, 1.8-6.2), azathioprine/6-mercaptopurine (OR, 3.1; 95% CI, 1.7-5.5), and infliximab (OR, 4.4; 95% CI, 1.2-17.1) were associated individually with significantly increased odds for opportunistic infection. Multivariate analysis indicated that use of any one of these drugs yielded an OR of 2.9 (95% CI, 1.5-5.3), whereas use of 2 or 3 of these drugs yielded an OR of 14.5 (95% CI, 4.9-43) for opportunistic infection. The relative risk of opportunistic infection was greatest in IBD patients seen at older than 50 years of age (OR, 3.0; 95% CI, 1.2-7.2, relative to those 24 years or younger). No patient died from opportunistic infection. CONCLUSIONS Immunosuppressive medications, especially when used in combination, and older age are associated with increased risk of opportunistic infections. The absolute risk of opportunistic infection in IBD patients remains to be determined, as does any potential benefit of any preventive strategy.

The Epidemiology of Community-Acquired Clostridium difficile Infection: A Population-Based Study

OBJECTIVES:Clostridium difficile infection (CDI) is a common hospital-acquired infection with increasing incidence, severity, recurrence, and associated morbidity and mortality. There are emerging data on the occurrence of CDI in nonhospitalized patients. However, there is a relative lack of community-based CDI studies, as most of the existing studies are hospital based, potentially influencing the results by referral or hospitalization bias by missing cases of community-acquired CDI.METHODS:To better understand the epidemiology of community-acquired C. difficile infection, a population-based study was conducted in Olmsted County, Minnesota, using the resources of the Rochester Epidemiology Project. Data regarding severity, treatment response, and outcomes were compared in community-acquired vs. hospital-acquired cohorts, and changes in these parameters, as well as in incidence, were assessed over the study period.RESULTS:Community-acquired CDI cases accounted for 41% of 385 definite CDI cases. The incidence of both community-acquired and hospital-acquired CDI increased significantly over the study period. Compared with those with hospital-acquired infection, patients with community-acquired infection were younger (median age 50 years compared with 72 years), more likely to be female (76% vs. 60%), had lower comorbidity scores, and were less likely to have severe infection (20% vs. 31%) or have been exposed to antibiotics (78% vs. 94%). There were no differences in the rates of complicated or recurrent infection in patients with community-acquired compared with hospital-acquired infection.CONCLUSIONS:In this population-based cohort, a significant proportion of cases of CDI occurred in the community. These patients were younger and had less severe infection than those with hospital-acquired infection. Thus, reports of CDI in hospitalized patients likely underestimate the burden of disease and overestimate severity.

An outbreak of Mycobacterium chelonae infections in tattoos

Nontuberculous mycobacteria infections may occur after cutaneous procedures. Review of the medical records of patients who developed a rash within a tattoo revealed 6 patients with skin infections caused by Mycobacterium chelonae after receiving tattoos by one artist at a single tattoo establishment. The interval between tattoo placement and the skin findings was 1 to 2 weeks. All patients received alternate diagnoses before mycobacterial infection was identified. Skin findings included pink, red, or purple papules; papules with scale; pustules; granulomatous papules; and lichenoid papules and plaques. Histopathologic examination revealed granuloma, lymphohistiocytic infiltrate, or mixed inflammation; acid-fast bacilli stains produced negative results. Diagnosis was made by culture in 3 patients, histopathology in two patients, and clinical/epidemiologic association in one patient. The M chelonae isolates were clarithromycin susceptible, and the infections responded to macrolide antibiotics. Physicians should consider mycobacterial infections in patients with skin findings within a new tattoo.

Asymptomatic Clostridium difficile colonization in a tertiary care hospital: Admission prevalence and risk factors

BACKGROUND The role of Clostridium difficile (CD) carriers in health care-associated CD transmission has been identified as an area needing research. We investigated the prevalence of, and risk factors for, asymptomatic CD colonization at hospital admission. METHODS Adults admitted to a tertiary care hospital in Minnesota on predetermined study days between March 1 and April 30, 2009, and without symptoms of C difficile infection, were eligible. The first stool sample after admission was requested from each consenting patient and tested for toxigenic CD using polymerase chain reaction (PCR) that detects tcdC. Clinical data were obtained through interviews and chart reviews. RESULTS Of 320 participants, 31 (9.7%) were positive for toxigenic CD. Using multivariate logistic regression, independent predictors of CD colonization were recent hospitalization (odds ratio [OR], 2.45; 95% confidence interval [CI]: 1.02-5.84), chronic dialysis (OR, 8.12; 95% CI: 1.80-36.65), and corticosteroid use (OR, 3.09; 95% CI: 1.24-7.73). Screening patients with risk factors (48% participants) would identify 74% (95% CI: 55%-88%) of CD carriers. CONCLUSION Asymptomatic CD colonization at hospital admission was detected in nearly 1 of 10 patients. The majority of colonized patients had one or more identifiable risk factors. These data could provide the basis for designing studies of targeted surveillance for C difficile.

A Targeted Strategy to Wipe Out Clostridium difficile

This study evaluated daily cleaning with germicidal bleach wipes on wards with a high incidence of hospital-acquired Clostridium difficile infection (CDI). The intervention reduced hospital-acquired CDI incidence by 85%, from 24.2 to 3.6 cases per 10,000 patient-days, and prolonged the median time between hospital-acquired CDI cases from 8 to 80 days.

Safety and Durability of RBX2660 (Microbiota Suspension) for Recurrent Clostridium difficile Infection: Results of the PUNCH CD Study

BACKGROUND Managing recurrent Clostridium difficile infection (CDI) presents a significant challenge for clinicians and patients. Fecal microbiota transplantation (FMT) is a highly effective therapy for recurrent CDI, yet availability of a standardized, safe, and effective product has been lacking. Our aim in this study was to assess the safety and effectiveness of RBX2660 (microbiota suspension), a commercially prepared FMT drug manufactured using standardized processes and available in a ready-to-use format. METHODS Patients with at least 2 recurrent CDI episodes or at least 2 severe episodes resulting in hospitalization were enrolled in a prospective, multicenter open-label study of RBX2660 administered via enema. Intensive surveillance for adverse events (AEs) was conducted daily for 7 days following treatment and then at 30 days, 60 days, 3 months, and 6 months. The primary objective was product-related AEs. A secondary objective was CDI-associated diarrhea resolution at 8 weeks. RESULTS Of the 40 patients enrolled at 11 centers in the United States between 15 August 2013 and 16 December 2013, 34 received at least 1 dose of RBX2660 and 31 completed 6-month follow-up. Overall efficacy was 87.1% (16 with 1 dose and 11 with 2 doses). Of 188 reported AEs, diarrhea, flatulence, abdominal pain/cramping, and constipation were most common. The frequency and severity of AEs decreased over time. Twenty serious AEs were reported in 7 patients; none were related to RBX2660 or its administration. CONCLUSIONS Among patients with recurrent or severe CDI, administration of RBX2660 via enema appears to be safe and effective. CLINICAL TRIALS REGISTRATION NCT01925417.

Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection: Mayo Clinic in Arizona Experience

OBJECTIVE To report the initial experience of treating recurrent Clostridium difficile infection (CDI) with fecal microbiota transplant (FMT) at Mayo Clinic in Arizona. PATIENTS AND METHODS The study retrospectively reviewed FMTs performed at Mayo Clinic in Arizona between January 1, 2011, and January 31, 2013. All the recipients had multiple recurrent CDIs unresponsive to traditional antibiotic drug therapy. A standardized protocol was developed to identify patients, screen donors, perform FMT, and determine outcomes via telephone surveys. RESULTS Thirty-one patients (mean ± SD age, 61.26±19.34 years) underwent FMT. Median time from index infection to FMT was 340 days. Ninety-seven percent (29 of 30) of patients reported substantial improvement or resolution of diarrhea (median time to improvement, 3 days), 74% (17 of 23) reported improvement or resolution of abdominal pain (median time to improvement, 3 days), and 55% (16 of 29) had improvement or resolution of fatigue (median time to improvement, 6 days). Three patients underwent repeated FMT owing to persistent symptoms; 2 reported improvement in diarrhea with the second therapy. No serious adverse events directly related to FMT were reported. CONCLUSION A standardized regimen of FMT for recurrent CDI is safe, is highly effective, and can be provided using a relatively simple protocol.

High prevalence of tcdC deletion-carrying Clostridium difficile and lack of association with disease severity

We assessed the prevalence of tcdC deletion-carrying Clostridium difficile using a stool polymerase chain reaction (PCR) assay that detects previously described 18- and 39-bp deletions (J. Clin. Microbiol. 2008;46:1996). We divided inpatients into 2 groups, those for whom the assay detected a deletion in tcdC and those for whom no deletion was detected. We compared risk factors (antibiotic use, hospitalization, nursing home stay, immunocompromise, age >65 years), complications (pseudomembranous colitis, toxic megacolon, colonic perforation, colectomy, and intensive care unit admission), duration of antibiotic treatment, and 30-day mortality between the groups. Forty-two of 141 patients had deletion-positive C. difficile. Prior nursing home stay and age >65 years were significantly more common in the deletion-positive group. Other risk factors, complications, antibiotic duration, and mortality did not differ significantly. Deletion-carrying C. difficile was commonly present but not associated with more severe disease and not markedly different in terms of risk factor profile. Severity of disease was relatively low, regardless of the presence or absence of a deletion.

Characteristics of Patients with Mild to Moderate Primary Pulmonary Coccidioidomycosis

Convalescence is prolonged, regardless of whether the patient receives treatment.

Histoplasmosis infection in patients with rheumatoid arthritis, 1998-2009.

BackgroundPatients with rheumatic diseases including rheumatoid arthritis (RA) are at increased risk for infections related to both the disease and its treatments. These include uncommonly reported infections due to histoplasmosis.MethodsMedical record review of all patients with a diagnosis of RA who developed new histoplasmosis infection in an endemic region between Jan 1, 1998 and Jan 30, 2009 and who were seen at Mayo Clinic in Rochester, Minnesota was performed.ResultsHistoplasmosis was diagnosed in 26 patients. Most patients were on combination therapies; 15 were on anti-tumor necrosis factor (anti-TNF) agents, 15 on corticosteroids and 16 on methotrexate. Most received more than 6 months of itraconazole and/or amphotericin treatment. Two patients died of causes unrelated to histoplasmosis. Anti-TNF treatment was restarted in 4/15 patients, with recurrence of histoplasmosis in one.ConclusionsIn this largest single center series of patients with RA and histoplasmosis in the era of immunomodulatory therapy, we found that most patients had longstanding disease and were on multiple immunomodulatory agents. Most cases were pulmonary; typical signs and symptoms of disease were frequently lacking.