Nosocomial infections are public health threats with often grave human costs. Because implementing screening and best outbreak response practices is costly for health care organizations, allocating resources for interventions requires consensus among stakeholders with a plurality of perspectives about how to weigh prospective interventions' risks and benefits. Economic analysis can facilitate decision making but is relatively new in nosocomial infection prevention and control. This article describes features of and reasons for economic analysis in this specific area and focuses on emerging challenges in antimicrobial stewardship.To claim one AMA PRA Category 1 Credit TM for the CME activity associated with this article, you must do the following: (1) read this article in its entirety, (2) answer at least 80 percent of the quiz questions correctly, and (3) complete an evaluation. The quiz, evaluation, and form for claiming AMA PRA Category 1 Credit TM are available through the AMA Ed Hub TM .
The red secTion 359 What's Hot in the red journal t h i s m o n t hColonization With Toxinogenic C. difficile upon Hospital admission, and risk of Infection: a Systematic review and Meta-analysis Clostridium difficile continues to be a major scourge of hospitalized patients. This meta-analysis used 19 studies incorporating more than 8,700 patients. The pooled prevalence of colonization with C. difficile was 8.1%, with an increasing trend over time, and was slightly higher at 10% in North American studies. Patients who became colonized upon hospital admission were much more likely to develop C. difficile infections, at a rate almost six times greater than in those who were not colonized. The absolute risk for C. difficile infection in colonized patients was 21%, much greater than in non-colonized patients. The risk for colonization was determined largely by prior hospitalization, not prior antibiotic or proton pump inhibitor use or even prior C. difficile infection. The authors conclude that patients who are carriers of toxigenic C. difficile are at substantially increased risk of C. difficile infection. These results may have implications for hospital management of this quite severe iatrogenic illness. See page 381 risk Factors on the development of new-onset Gastroesophageal reflux Symptoms. a Population-Based Prospective Cohort Study: The HunT StudyThis study assessed risk factors for recent-onset gastroesophageal reflux symptoms. It is based on a prospective adult population in Norway, with a 61% response rate, encompassing more than 29,000 individuals. Five hundred individuals who had no reflux at the beginning had severe reflux symptoms at follow-up. Increasing age was positively associated, but, interestingly, male gender and high education were negatively associated, with new-onset gastroesophageal reflux disease (GERD) symptoms. Body mass index gain was important, even if the patients were thin at the beginning, and any history of smoking was associated with reflux symptoms. The combination of tobacco smoking cessation with weight gain was also associated with reflux. The authors conclude that, surprisingly, female sex was associated with an increase in GERD symptoms, as were increasing age, lower education, gain in body mass index, and having ever been a smoker. In particular, the observation that tobacco smoking cessation associated with weight gain was associated with reflux symptoms suggests that prospective intervention may be worth considering in patients who stop smoking. See page 393
ImportanceStaphylococcus aureus bacteremia is associated with a significant burden of mortality, morbidity, and health care costs. Infectious disease consultation may be associated with reduced mortality and bacteremia recurrence rates.ObjectiveTo evaluate the cost-effectiveness of infectious disease consultation for Staphylococcus aureus bacteremia.Design, Setting, and ParticipantsIn this economic evaluation, a decision-analytic model was constructed comparing infectious disease consult with no consult. The population was adult hospital inpatients with Staphylococcus aureus bacteremia diagnosed with at least 1 positive blood culture. Cost-effectiveness was calculated as deaths averted and incremental cost-effectiveness ratios. Uncertainty was addressed by plotting cost-effectiveness planes and acceptability curves for various willingness-to-pay thresholds. Costs and outcomes were calculated for a time horizon of 6 months. The analysis was performed from a societal perspective and included studies that had been published by January 2022.InterventionsPatients received or did not receive formal bedside consultation after positive blood cultures for Staphylococcus aureus bacteremia.Main Outcomes and MeasuresThe main outcomes were incremental difference in effectiveness (survival probabilities), incremental difference in cost (US dollars) and incremental cost-effectiveness ratios (US dollars/deaths averted).ResultsThis model included 1708 patients who received consultation and 1273 patients who did not. In the base-case analysis, the cost associated with the infectious disease consult strategy was $54 137.4 and the associated probability of survival was 0.77. For the no consult strategy, the cost was $57 051.2, and the probability of survival was 0.72. The incremental difference in cost between strategies was $2913.8, and the incremental difference in effectiveness was 0.05. Overall, consultation was associated with estimated savings of $55 613.4/death averted (incremental cost-effectiveness ratio, −$55613.4/death averted). In the probabilistic analysis, at a willingness-to-pay threshold of $50 000, infectious disease consult was cost-effective compared with no consult in 54% of 10 000 simulations. In cost-effectiveness acceptability curves, the consult strategy was cost-effective in 58% to 73%) of simulations compared with no consult for a willingness-to-pay threshold ranging from $0 to $150 000.Conclusions and RelevanceThese findings suggest that infectious disease consultation may be a cost-effective strategy for management of Staphylococcus aureus bacteremia and that it is associated with health care cost-savings.
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4134 Invasive fungal infections/disease (IFI/IFD) are a major cause of morbidity and mortality after hematopoietic stem cell transplants (HCT), but their incidence and risk factors are not well defined. We performed a retrospective review of 270 consecutive adults (152 M/118 F), median age 53 (18–75) years, with hematologic malignancy receiving allogeneic HCT at Massachusetts General Hospital between 2000 to 2010 to determine the incidence, risk factors and outcomes of patients that developed IFD. All patients received antifungal prophylaxis from the start of conditioning until Day +100; 90% received fluconazole 400 mg daily. We defined IFD using the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, defining proven cases as evidence of fungal elements in a sterile tissue, and probable as presence of fungal elements in non sterile tissue or positive Galactomannan antigen or β-D-Glucan test in patients with clinical features suggestive of IFI. Diagnoses were Acute Myeloid Leukemia (34%), Non Hodgkin's Lymphoma (24%), Myelodysplastic syndrome (15%), Acute Lymphoblastic Leukemia (8%), Chronic Lymphocytic Leukemia (5%), Myeloproliferative disorders, Hodgkin Lymphoma and Multiple Myeloma (4% each), and others (2%). 15% had a prior autologous transplant. Conditioning included reduced intensity (64%) or myeloablative (36%) regimens. Donor source was fully HLA matched (MRD) in 60%, matched unrelated (MUD) in 20%, Haploidentical in 12% and Cord Blood in 8%. 41% received ATG based aGVHD prophylaxis vs non ATG based in 59%. 11% were diabetic, while 6% had a history of IFD prior to transplant. 55% received systemic steroids for GVHD and 34% received TPN during transplant course. Median follow up was 28 (1.0–141.0) months. 49 distinct episodes of IFI were observed in 40 subjects (15%). Aspergillus spp (47%) was most frequently encountered, followed by Candida spp (43%). Mucor was isolated in 1 case. Among the Candida spp, the majority (52%) were non albicans- Candida glabrata (8) vs 1 each of Candida krusei, Candida tropicalis and Candida parapsilosis. Most frequently infected site was the lungs (69%), followed by the blood stream and paranasal sinuses (14% each), and GI tract (4%). Spleen (hepatosplenic candidiasis), kidneys and brain were affected in 1 patient each. In 6%, involvement of both the lungs and sinuses was observed. The estimated probability of early IFD (within 100 days post transplant) was 7%. Patients and transplant factors, including age, diagnosis, prior autologous transplant, type of conditioning regimen, type of aGVHD prophylaxis, donor type, CD34+ cell dose infused, history of diabetes or prior IFD, systemic use of steroids for GVHD and TPN administration, were examined to determine risk factors for developing IFD. In multivariable analysis, haploidentical donor transplants (HR 3.48, 95% CI 1.35–8.99, p=0.01) and the development of Grade III and IV aGVHD (HR 3.32, 95% CI 1.23–9.01, p=0.02) were risk factors for the development of IFD. Conversely, higher CD34+ cell dose infused was associated with a lower risk of IFD (HR 0.80, 95% CI 0.68–0.94, p=0.01, per 1×10⋀6 cells/kg increase). The overall mortality (OM) of patients with IFD was 41%. A higher non-relapse mortality (NRM) was observed for patients with IFD as compared to patients without IFD, 55% vs 18% (HR 3.76, 95% CI 2.03–6.97, p<0.001). In multivariable analysis, accounting for CD34+ cell count, donor type and Grade III-IV aGVHD, the effect of IFI on NRM remained significant (HR 3.32, 95% CI 1.65–6.67, p=0.001). Patients with IFD had lower overall survival (OS), 16 months as opposed to 50 months for patients without IFD. In summary, 1) The risk of IFD after allogeneic HCT was 15%; 2) Patients with IFD have a high mortality after allogeneic HCT; 3) Haploidentical donor type and development of Grades III-IV GVHD are risk factors for IFD; 4) A higher CD34+ cell dose may be protective against IFD; 5) Prior IFD did not predict for higher risk of IFD or higher mortality, suggesting these patients should not be excluded from allogeneic HCT. Further studies looking at alternate aGVHD prophylaxis regimens, strategies to increase cell dose infused and better antifungal prophylaxis for these high risk patients are needed to lessen this potentially life threatening complication. Disclosures: Mylonakis: T2 Biosystems: Research Funding; Astellas inc : Research Funding.
Background: Invasive aspergillosis (IA) is associated with significant morbidity and mortality among hematopoietic-stem cell transplant (HSCT) recipients. Timely and accurate diagnosis of an active infection is needed in order to initiate targeted antifungal therapy. Although previous studies have assessed the performance of Aspergillusspp. PCR with promising findings, PCR has not yet been incorporated in the diagnostic algorithms by the guideline issuing organizations. Aim: Our goal was to evaluate PCR as a screening or a confirmatory tool for the diagnosis of IA among HSCT patients and to determine the different parameters that could contribute to contradictory reports from the literature regarding PCR performance. Thus, we performed a meta-analysis of clinical trials that evaluated the accuracy of PCR for IA performed on serum and whole blood of HSCT patients. Methods: We performed a bivariate meta-analysis of diagnostic data for Aspergillus spp. PCR on blood specimens across HSCT patients. We included all studies involving human subjects that assessed the performance of any PCR assay for IA on whole blood or serum and that used as reference standard the EORTC/MSG criteria. We performed 2 separate analyses either including or excluding the cases that were defined as “possible”. When possible cases where included they were classified as negative. Out of 37 total studies, 25 met strict quality criteria and were included. Results: 25 studies with 2,595 patients were analyzed. Six studies performed PCR on serum (23%) and the remaining used whole blood assays (77%). The pooled diagnostic performance of whole blood and serum PCR was moderate, with a sensitivity of 84% (95% CI 75%-91%). Specificity was 76% (95% CI 65%-84%) when possible cases were included and 85% (95% CI 74%-91%) when excluded, suggesting that a positive or negative result is unable on its own to confirm or exclude a suspected infection. In subgroup analysis, the performance of PCR on serum was not significantly different from whole blood when possible cases were included. Interestingly, exclusion of possible cases revealed higher specificity of serum PCR (94% vs. 80%, meta-regression p-value=0.05) over whole blood without altering the sensitivity (79% vs. 85%, meta-regression p-value=0.4) and high positive likelihood ratio (LR+=12.6) suggesting that serum PCR could be used as a confirmatory test. No methodological parameter significantly affected the performance of PCR. Importantly, PCR specificity was greatly increased when 2 positive PCR results were used to define positivity (73% vs. 95%, respectively), giving a high positive likelihood ratio of 12.8, whereas sensitivity decreased (85% vs 64%, respectively). Importantly, the European AspergillusPCR Initiative (EAPCRI) recommendations improved even further the performance of PCR when at least two positive specimens were used to define ‘PCR positivity’. Conclusions: Two positive PCR results should be considered highly indicative of an active Aspergillus spp. infection in HSCT patients. Use of the EAPCRI recommendations by clinical laboratories can further enhance PCR performance. Disclosures No relevant conflicts of interest to declare.
Thrombocytopenia in Systemic Lupus Erythematosus is a common clinical manifestation affecting up to one third of patients in published cohorts. Antiplatelet antibodies, antithrombopoietin antibodies and faulty hemopoiesis have been implicated among other immunologic and non-immunologic causes. This mini review is an uptodate summary of these immunologic phenomena.
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