T2 Magnetic Resonance Assay: Overview of Available Data and Clinical Implications

Invasive candidiasis is a common healthcare-associated infection with a high mortality rate that can exceed 60% in cases of septic shock. Blood culture performance is far from ideal, due to the long time to positivity and suppression by antifungal agents. The T2 Magnetic Resonance (T2MR) assay is an FDA-approved qualitative molecular diagnostic method that can detect and speciate the 5 most common Candida spp.; namely, Candida albicans, Candida glabrata, Candida parapsilosis, Candida tropicalis, and Candida krusei, in approximately 5 h. In a multicenter clinical trial that included both a prospective and a contrived arm to represent the full range of clinically relevant concentrations of Candida spp., T2MR demonstrated a sensitivity and specificity of 91.1% and 98.1%, respectively. The utility of T2MR in candidemia depends on the prevalence of disease in each clinical setting. In intensive care units and other high-prevalence settings, the incorporation of T2MR in diagnostic algorithms is very appealing. T2MR is expected to allow timely initiation of antifungal therapy and help with anti-fungal stewardship. In low-prevalence settings, the positive predictive value of T2MR might not be enough to justify initiation of antifungal treatment in itself. The performance of T2MR has not been studied in cases of deep-seated candidiasis. Despite some promising evidence in published clinical trials, further studies are needed to determine the performance of T2MR in invasive candidiasis without candidemia. Overall, experience with T2MR in everyday clinical practice is evolving but, in the right setting, this technology is expected to provide “actionable information” for the management of patients evaluated for candidemia

Cost-effectiveness of molecular diagnostic assays for the therapy of severe sepsis and septic shock in the emergency department.

ObjectivesSepsis presents a major burden to the emergency department (ED). Because empiric inappropriate antimicrobial therapy (IAAT) is associated with increased mortality, rapid molecular assays may decrease IAAT and improve outcomes. We evaluated the cost-effectiveness of molecular testing as an adjunct to blood cultures in patients with severe sepsis or septic shock evaluated in the ED.MethodsWe developed a decision analysis model with primary outcome the incremental cost-effectiveness ratio expressed in terms of deaths averted. Costs were dependent on the assay price and the patients' length of stay (LOS). Three base-case scenarios regarding the difference in LOS between patients receiving appropriate (AAT) and IAAT were described. Sensitivity analyses regarding the assay cost and sensitivity, and its ability to guide changes from IAAT to AAT were performed.ResultsUnder baseline assumptions, molecular testing was cost-saving when the LOS differed by 4 days between patients receiving IAAT and AAT (ICER -$7,302/death averted). Our results remained robust in sensitivity analyses for assay sensitivity≥52$270. In the extreme case that the LOS of patients receiving AAT and IAAT was the same, the ICER remained≤$20,000/death averted for every studied sensitivity (i.e. 0.5-0.95), panel efficiency≥34$313. For 2 days difference in LOS, the bundle approach was dominant when the assay cost was≤$135 and the panel efficiency was≥77%.ConclusionsThe incorporation of molecular tests in the management of sepsis in the ED has the potential to improve outcomes and be cost-effective for a wide range of clinical scenarios

Extra-urogenital infection by Mycoplasma hominis in transplant patients: two case reports and literature review

Abstract Background Mycoplasma hominis is a facultative anaerobic bacterium commonly present in the urogenital tract. In recent years, M. hominis has increasingly been associated with extra-urogenital tract infections, particularly in immunosuppressed patients. Detecting M. hominis in a diagnostic laboratory can be challenging due to its slow growth rate, absence of a cell wall, and the requirements of specialized media and conditions for optimal growth. Consequently, it is necessary to establish guidelines for the detection of this microorganism and to request the appropriate microbiological work-up of immunosuppressed patients. Case Presentation We hereby present two cases of solid organ transplant patients who developed M. hominis infection. Microscopic examination of the bronchial lavage and pleural fluid showed no microorganisms. However, upon inoculating the specimens onto routine microbiology media, the organism was successfully identified and confirmation was performed using 16S rDNA sequencing. Both patients received appropriate treatment resulting in the resolution of M. hominis infection. Conclusions The prompt detection of M. hominis in a clinical specimen can have a significant impact on patient care by allowing for early intervention and ultimately resulting in more favorable clinical outcomes, especially in transplant patients

Association of Community Factors with Hospital-onset Clostridioides (Clostridium) difficile Infection: A Population Based U.S.-wide Study

Background: Clostridioides (Clostridium) difficile ranks first among the pathogens of hospital-acquired infections with hospital-based preventive strategies being only partially successful in containing its spread. Methods: We performed a spatial statistical analysis to examine the association between population characteristics and parameters of community healthcare practice and delivery with hospital-onset Clostridioides (Clostridium) difficile infection (HO-CDI), using data from the Medicare Hospital Compare, Medicare Provider Utilization Part D, and other databases. Among the areas with the highest HO-CDI rates (“hot spots”), we conducted a geographically weighted regression (GWR) to quantify the effect of the decrease in the modifiable risk factors on the HO-CDI rate. Findings: Percentage of population > 85 years old, community claims of antimicrobial agents and acid suppressants, and density of hospitals and nursing homes within the hospital service areas (HSAs) had a statistically significant association with the HO-CDI incidence (p < 0.001). The model including the community claims of antimicrobial agents and number of hospital centers per HSA km2 was associated with 10% (R2 = 0.10, p < 0.001) of the observed variation in HO-CDI rate. The hot spots were organized into 5 Combined Statistical areas that crossed state borders. The association of the antimicrobial claims and HO-CDI rate was as high as 71% in the Boston–Worcester–Providence area (R2 = 0.71, SD 0.19), with a 10% decrease in the rate of antimicrobial claims having the potential to lead to up to 23.1% decrease in the HO-CDI incidence in this area. Interpretation: These results outline the association of HO-CDI with community practice and characteristics of the healthcare delivery system and support the need to further study the effect of community and nursing home-based antimicrobial and acid suppressant stewardship programs in the rate of HO-CDI in geographic areas that may cross state lines. Keywords: Clostridium difficile, Clostridioides difficile, HO-CDI, Risk factors, Geographically weighted regression model, Spatial statistical analysi

Isolation of C. difficile Carriers Alone and as Part of a Bundle Approach for the Prevention of Clostridium difficile Infection (CDI): A Mathematical Model Based on Clinical Study Data.

Clostridium difficile infection is the most common hospital-acquired infection. Besides infected patients, carriers have emerged as a key player in C. difficile epidemiology. In this study, we evaluated the impact of identifying and isolating carriers upon hospital admission on the incidence of CDI incidence and hospital-acquired C. difficile colonization, as a single policy and as part of bundle approaches. We simulated C. difficile transmission using a stochastic mathematical approach, considering the contribution of carriers based on published literature. In the baseline scenario, CDI incidence was 6.18/1,000 admissions (95% CI, 5.72-6.65), simulating reported estimates from U.S. hospital discharges. The acquisition rate of C. difficile carriage was 9.72/1,000 admissions (95% CI, 9.15-10.31). Screening and isolation of colonized patients on admission to the hospital decreased CDI incidence to 4.99/1,000 admissions (95% CI, 4.59-5.42; relative reduction (RR) = 19.1%) and led to 36.2% reduction in the rate of hospital-acquired colonization. Simulating an antimicrobial stewardship program reduced CDI rate to 2.35/1,000 admissions (95% CI, 2.07-2.65). In sensitivity analysis, CDI incidence was less than 2.32/1,000 admissions (RR = 62.4%) in 95% of 1,000 simulations. The combined bundle, focusing on reducing C. difficile transmission from colonized patients and the individual risk of these patients to develop CDI, decreased significantly the incidence of both CDI and hospital-acquired colonization. Implementation of this bundle to current practice is expected to have an important impact in containing CDI

Summary of included studies and stratified prophylaxis data on outcome.

<p>(The complete study characteristics are available on S1 Table in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0114735#pone.0114735.s001" target="_blank">S1 Appendix</a>).</p><p>CsA = cyclosporine A; MTX = methotrexate; ATG = antithymocyte globulin; MP = methyl-prednisolone; Pse = systemic corticosteroid (prednisolone or methylprednisolone); BDP =  oral beclomethasone propionate. MMF =  mycophenolate mofetil, NR = not reported.</p><p>Summary of included studies and stratified prophylaxis data on outcome.</p

Network of direct (solid lines) and indirect comparisons (dashed lines) of different treatments evaluated for acute GvHD prophylaxis.

<p>The thickness of connecting lines is proportional to the number of available direct comparisons.</p

Forest plot of direct comparisons for the primary outcome (II-IV GvHD).

<p>Forest plot of direct comparisons for the primary outcome (II-IV GvHD).</p

Graft-Versus-Host Disease Prophylaxis after Transplantation: A Network Meta-Analysis

<div><p>Background</p><p>Graft-versus-host Disease (GvHD) prophylaxis after allogeneic hematopoietic stem-cell transplantation (HSCT) is an ongoing effort but relative effects of different policies are not systematically explored.</p><p>Methods</p><p>We systematically reviewed 30-year evidence on GvHD prophylaxis and quantified the relative effect of different policies using a network meta-analysis. We searched PubMed and the Cochrane Library for randomized studies on the topic. The primary outcome of interest was grade II-IV acute GvHD over 0 or I (with odds ratio OR <1 denoting benefit).</p><p>Findings</p><p>Thirty-three eligible studies that enrolled 3,440 patients (published up to June 2014), provided data on seven immunosuppressive drugs namely cyclosporin A (CsA), methotrexate (MTX), anti-thymocyte globulin (ATG), mycophenolate mofetil (MMF), tacrolimus, sirolimus or corticosteroids and their combinations to calculate 14 direct and 21 indirect effects. The majority of trials (32/33) referred to myeloablative conditioning and sibling transplants (25/33). Tacrolimus/MTX (OR 0.44; 95% 0.27–0.70, number needed to treat to benefit, i.e. to avert a case of II-IV GvHD, NNTB = 5) and ATG/CsA/MTX (OR 0.45; 95%CI 0.26–0.78; NNTB = 5) were superior over CsA/MTX. ATG/CsA/MTX did not differ from tacrolimus/MTX (indirect evidence). Sirolimus-based prophylaxis outperformed CsA/MTX (OR 0.10; 95%CI 0.02–0.49, NNTB = 4) and marginally outperformed tacrolimus/MTX (OR 0.22; 95%CI 0.05–1.11). Add-on corticosteroids had no benefit over CsA/MTX.</p><p>Conclusions</p><p>Tacrolimus/MTX and ATG/CsA/MTX were the outperformers over CsA/MTX, but sirolimus-based regimens showed also potential. More randomized data are needed for reduced-intensity conditioning, as well as for MMF and sirolimus-containing regimens.</p></div

Forest plot of direct comparisons for the secondary outcome (III-IV GvHD).

<p>Forest plot of direct comparisons for the secondary outcome (III-IV GvHD).</p