Pneumocystis jirovecii pneumonia (PJP) is an important opportunistic infection that has been increasingly reported in patients with rheumatic disease. Reported incidence among patients taking TNF inhibitors (TNFi) has varied, but has usually been low. Still, disease causes significant mortality among those affected and must be considered in patients with rheumatological disease presenting with dyspnea and cough. Diagnosis can be difficult in the non-HIV population, and our understanding of the epidemiology and natural history after exposure is changing. Trimethoprim-sulfamethoxazole is believed to be the most effective agent for treatment and prophylaxis, but is associated with significant adverse effects. Given the low incidence reported in most studies of patients on TNFi, prophylaxis is probably not beneficial for this patient population as a whole.
BackgroundFecal microbiota transplants (FMT) are an effective treatment for patients with gut microbe dysbiosis suffering from recurrent C. difficile infections. To further understand how FMT reconstitutes the patient’s gut commensal microbiota, we have analyzed the colonization potential of the donor, recipient and recipient post transplant fecal samples using transplantation in gnotobiotic mice.ResultsA total of nine samples from three human donors, recipient’s pre and post FMT were transplanted into gnotobiotic mice. Microbiome analysis of three donor fecal samples revealed the presence of a high relative abundance of commensal microbes from the family Bacteriodaceae and Lachnospiraceae that were almost absent in the three recipient pre FMT fecal samples (<0.01 %). The microbe composition in gnotobiotic mice transplanted with the donor fecal samples was similar to the human samples. The recipient samples contained Enterobacteriaceae, Lactobacillaceae, Enterococcaceae in relative abundance of 43, 11, 8 %, respectively. However, gnotobiotic mice transplanted with the recipient fecal samples had an average relative abundance of unclassified Clostridiales of 55 %, approximately 7000 times the abundance in the recipient fecal samples prior to transplant. Microbiome analysis of fecal samples from the three patients early (2–4 weeks) after FMT revealed a microbe composition with the relative abundance of both Bacteriodaceae and Lachnospiraceae that was approximately 7 % of that of the donor. In contrast, gnotobioitc mice transplanted with the fecal samples obtained from the three at early times post FMT revealed increases in the relative abundance of Bacteriodaceae and Lachnospiraceae microbe compositions to levels similar to the donor fecal samples. Furthermore, the unclassified Clostridiales in the recipient samples post FMT was reduced to an average of 10 %.ConclusionWe have used transplantation into gnotobiotic mice to evaluate the colonization potential of microbiota in FMT patients early after transplant. The commensal microbes present at early times post FMT out competed non-commensal microbes (e.g. such as unclassified Clostridiales) for niche space. The selective advantage of these commensal microbes to occupy niches in the gastrointestinal tract helps to explain the success of FMT to reconstitute the gut microbe community of patients with recurrent C. difficile infections.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-015-0622-2) contains supplementary material, which is available to authorized users.
We used two different infection models to investigate the kinetics of the PcpA-dependent pneumococcal disease in mice. In a bacteremic pneumonia model, we observed a PcpA-dependent increase in bacterial burden in the lungs, blood, liver, BAL and spleens of mice at 24-hrs post infection. This PcpA-dependent effect on bacterial burden appeared earlier (within 12-hrs) in the focal-pneumonia model, which lacks bacteremia or sepsis. Histological changes show that the ability of pneumococci to make PcpA was associated with unresolved inflammation in both models of infection. Using our bacteremic pneumonia model we further investigated the effects of PcpA on recruitment of innate immune regulatory cells. The presence of PcpA was associated with increased IL-6 levels, suppressed production of TNF-related apoptosis - inducing ligand (TRAIL) and reduced infiltration of polymorphonuclear cells. The ability of pneumococci to make PcpA negatively modulated both the infiltration and apoptosis of macrophages and the recruitment of myeloid-derived suppressor-like cells (MDSCs). The latter have been shown to facilitate clearance and control of bacterial pneumonia. Taken together, the ability to make PcpA was strongly associated with increased bacterial burden, inflammation and negative regulation of innate immune cell recruitment to the lung tissue during bacteremic pneumonia.
BackgroundTumor Necrosis Factor inhibitors (TNFi) have dramatically improved the outlook for patients with inflammatory arthritides and bowel disease (IBD), but are associated with increased infection risks, including tuberculosis (TB). Pediatric inflammatory diseases are uncommon, and the risk of TB in children taking TNFi remains unclear. The objective of this study was to report the incidence of TB disease among TNFi recipients at a single pediatric medical center serving most of Alabama compared to that of the general population of Alabama children.MethodsInstances of TNFi usage among patients under age 20 years from July 1, 2007 through April 17, 2015 were captured from electronic health records at Children’s of Alabama (CoA), which has the only pediatric rheumatology clinic in Alabama, and where a substantial number of children in Alabama with inflammatory bowel disease receive care., and reports of TB cases were obtained from the Alabama Department of Public Health (ADPH). Incidence was expressed as TB cases/10,000 person-years, using population estimates from the Alabama Center for Health Statistics.Results1033 Alabama patients at CoA who were residents of Alabama were identified who received TNFi for a total of 1564 person-years. One adolescent on TNFi developed severe extrapulmonary TB (incidence density = 6.4 per 10,000; 95% CI 0.9–45.4 per 10,000). Sixty-three cases occurred in persons not on TNFi (incidence density = 0.064 per 10,000; 95% CI 0.050–0.082 per 10,000).ConclusionsOne case of TB disease among TNFi-exposed children was identified for 1564 person-years in Alabama residents. Although rare, this is higher than expected relative to the general rate of TB in Alabama. Thus, continued diagnostic vigilance for TB in children taking TNFi is required.Trial registration numberNot applicable.
Introduction: A marked increase in hospitalizations for severe, injection-related infections (SIRI) has been associated with the opioid epidemic. Outpatient parenteral antibiotic therapy (OPAT) is typically not offered to persons with opioid use disorder (OUD) and SIRI, though increasing evidence suggests it may be feasible and safe. This study evaluates the efficacy and cost-effectiveness of an integrated care model combining Buprenorphine treatment of OUD with OPAT for SIRI (B-OPAT) compared with treatment as usual on key OUD, infectious disease, and health economic outcomes. B-OPAT expands and incorporates key elements of established clinical models, including inpatient initiation of buprenorphine for OUD, inpatient infectious disease consultation for SIRI, office-based treatment of OUD, and OPAT, and includes more frequent clinical outpatient visits than standard OPAT. A qualitative evaluation is included to contextualize effectiveness outcomes and identify barriers and facilitators to intervention adoption and implementation. Methods: B-OPAT is a single-site, randomized, parallel-group, superiority trial recruiting 90 adult inpatients hospitalized with OUD and SIRI who require at least 2 weeks of intravenous (IV) antibiotic therapy. After screening, eligible participants are randomized 1:1 to either discharge once medically stable to an integrated outpatient treatment care model combining Buprenorphine and OPAT (B-OPAT) or to Treatment As Usual (TAU). The primary outcome measure is the proportion of urine samples negative for illicit opioids in the 12 weeks after discharge from the hospital. Key secondary OUD outcomes include self-reported number of days of illicit opioid abstinence and 12-week retention in buprenorphine treatment. The infection outcomes are completion of recommended IV antibiotic therapy, peripherally inserted central catheter (PICC) complications, and readmission related to primary SIRI. Conclusions: The B-OPAT study will help address the important question of whether it is clinically effective and cost-effective to discharge persons with OUD and SIRI to an integrated outpatient care model combining OUD treatment with OPAT relative to TAU (Clinicaltrials.gov Identifier: NCT04677114).
Background Infection is a major complication of placement of left ventricular assist devices (LVADs) for patients with end stage heart failure. This study aimed to identify risk factors and evaluate outcomes of early LVAD specific and related infections in a community teaching hospital. Methods This was a single-center, retrospective cohort study that included adult patients with placement of LVAD from October 2012 – December 2019. LVAD specific infection was defined as a pump, cannula, pocket, or percutaneous driveline infection and LVAD related infection was defined as infective endocarditis, mediastinitis, or bloodstream infection. The primary outcome was early LVAD specific or related infection within 90 days of implantation. Secondary outcomes included time to infection, risk factors of and time to recurrent infection, and time to death. Multivariate logistic regression was used to ascertain risk factors for early infection. Cox regression was used to ascertain association with time to outcome variables. Results Of 160 patients who had LVADs placed during the study period, 26 experienced early LVAD infection. The majority of infections were caused by Staphylococcus spp. (32.1%). Risk factors for early infection are summarized in Table 1. Risk factors identified included placement of HeartMate III device when compared to HeartMate II and BMI > 40kg/m2. Increased hazard rate of infection was demonstrated for patients with HeartWare and HeartMate III devices compared to HeartMate II (HR 2.344; 95% CI 1.22,4.496; p-value 0.01; and HR 2.858; 95% CI 1.231, 6.635; p-value 0.015, respectively), those with BMI >40 (HR 2.437; 95% CI 1.131, 5.252; p-value 0.023), and those with history of diabetes (HR 1.736; 95% CI 1.012, 2.987; p-value 0.045). No risk factors were identified in the multivariate regression model for recurrent infection. Time to death was increased among patients with A1C > 6.4 at baseline (HR 1.028; 95% CI 1.002, 1.054; p-value: 0.032) and among patients who experienced early LVAD infection (HR 3.824; 95% CI 1.928, 7.584; p-value < 0.001). Conclusion HeartMate III device and BMI > 40kg/m2 were identified as risk factors for early LVAD infection. Time to mortality was decreased among patients that experienced an early LVAD infection. Disclosures Julie Ann Justo, PharmD, MS, BCPS-AQ ID, bioMerieux (Speaker’s Bureau)TRC Healthcare (Speaker’s Bureau)
BackgroundExperiential education opportunities, such as interprofessional practice, are currently limited in HIV care. This intentional interprofessional experiential education (IPEE) offering aimed to improve healthcare student attitudes, perceptions, and skills regarding interprofessional practice and HIV care.MethodsAn interprofessional team of faculty and clinicians designed a 2-week rotation, with each offering consisting of 6–9 students from 4 professions (medicine, nursing, pharmacy, social work). This intentional IPEE was delivered at a single ambulatory care infectious diseases clinic in Columbia, SC. It included time in clinic with providers from varying professions, didactic lectures, a peer health advocate session, and a team capstone project (i.e., simulated, then actual student team visit with an HIV-infected patient, plus note documentation/team presentation). Twelve offerings occurred from October 2016 to February 2019. Anonymous pre- and post-IPEE surveys were provided to each student at baseline and directly after to assess attitudes, perceptions, and skills regarding interprofessional practice and HIV care. Wilcoxon signed-rank tests were used to compare pre- vs. post-survey items. Multivariable logistic regression was used to evaluate predictors for interest in HIV as a specialty.ResultsOf 87 students, 84 (97%) completed both surveys (21 medicine, 25 nursing, 19 pharmacy, 19 social work). Attitudes toward healthcare teams significantly improved in 7/11 items (all P-values ≤ 0.019), teamwork perceptions improved in 5/8 items (P ≤ 0.017), and self-perceived team skills improved in all 6 items (P < 0.001). Students rated provider time in clinic as most valuable (mean 4.6, median 5 on 5-point Likert scale). Following the IPEE, the proportion of students interested in HIV care increased from 53% to 67% (P = 0.07). After adjusting for program year and profession, interest in HIV at baseline was a significant predictor of interest in HIV post-IPEE (aOR 8.2, 95% CI 2.6–25.5).ConclusionShort-term, intentional IPEE can positively impact student attitudes, perceptions, and skills regarding interprofessional practice and HIV care. Clinical educators should incorporate intentional HIV IPEE in healthcare curricula.Disclosures All Authors: No reported Disclosures.
Background Opioid overdose is the leading cause of injury-related death in the United States. Kentucky ranks in the top 5 states for overdose death and has one of the highest rates of acute hepatitis C (HCV). Fifty-four of Kentucky’s counties are among the 220 U.S. counties identified as high risk for rapid dissemination of HIV and HCV. Poverty, legal issues, and transportation are barriers to effective treatment of opioid use disorder (OUD) and related infections. The WRAP project (Wrap-around Recovery for Addiction and infectious Diseases project) is an ongoing multi-disciplinary program to expand access to OUD treatment at University of Kentucky HealthCare. This program provides social support including transportation assistance, case management, and counseling. Missed visits have been associated with multiple adverse outcomes. Methods We compared missed infectious diseases clinic visits (n=620) of patients enrolled in WRAP to those of patients who were referred and eligible, but not enrolled using chi-square tests for odds ratios. Results We enrolled 35% of eligible, referred patients. The majority (70%) of patients not enrolled were referred while inpatient and discharged before they could be enrolled. WRAP-enrolled patients missed 21% of visits, whereas WRAP-eligible, non-enrolled patients missed 31% of visits (OR 0.59, 95% CI 0.49 to 0.72, p-value < 0.001), Figure 1. This finding was consistent for WRAP-referred patients with a diagnosis of HIV who were also eligible for Ryan White support services: WRAP-enrolled patients missed 17% of visits and WRAP-eligible, non-enrolled patients missed 25% of visits (OR 0.26, 95% CI 0.20 to 0.35, p-value 0.002). For HCV patients who were mostly referred as outpatients, WRAP-enrolled patients missed 25% of visits while WRAP-eligible, non-enrolled patients missed 39% (OR 0.54, 95% CI 0.41 to 0.72 , p-value 0.0003), Figure 2. Figure 1. ID clinic visit attendance among WRAP eligible, non-enrolled and WRAP enrolled patients. WRAP-enrolled patients missed 21% of visits, whereas WRAP-eligible, non-enrolled patients missed 31% of visits (OR 0.59, 95% CI 0.49 to 0.72, p-value < 0.001). Figure 2. ID clinic attendance among WRAP eligible, non-enrolled and WRAP enrolled patients with HIV and hepatitis C primary diagnoses. A. WRAP-enrolled patients with a primary diagnosis of HIV missed 17% of visits and WRAP-eligible, non-enrolled patients missed 25% of visits (OR 0.26, 95% CI 0.20 to 0.35, p-value 0.002). B. WRAP-enrolled patients with a primary diagnosis of hepatitis C missed 25% of visits while WRAP-eligible, non-enrolled patients missed 39% (OR 0.54, 95% CI 0.41 to 0.72, p-value 0.0003). Conclusion Providing patients with social support services to address barriers to attending clinic visits was associated with fewer missed ID clinic visits. Higher engagement in care is a step towards implementing evidence-based treatment to lessen overdose deaths and injection-related infections. Future projects will include investigating whether WRAP enrollment is associated with fewer hospital admission and ER visits. Disclosures All Authors: No reported disclosures
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