It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
Hydroxychloroquine is an antimalarial drug being tested as a potential treatment for the novel coronavirus disease 2019 (COVID‐19) pandemic caused by the severe acute respiratory syndrome coronavirus ...2. Although the efficacy of hydroxychloroquine for COVID‐19 remains uncertain, it may serve as a potential prophylactic agent especially in those at high risk, such as healthcare workers, household contacts of infected patients, and the immunocompromised. Our aim was to identify possible hydroxychloroquine dosing regimens through simulation in those at high risk of infections by optimizing exposures above the in vitro generated half maximal effective concentration (EC50) and to help guide researchers in dose‐selection for COVID‐19 prophylactic studies. To maintain weekly troughs above EC50 in > 50% of subjects at steady‐state in a pre‐exposure prophylaxis setting, an 800 mg loading dose followed by 400 mg twice or 3 times weekly is required. In an exposure driven, post‐exposure prophylaxis setting, 800 mg loading dose followed in 6 hours by 600 mg, then 600 mg daily for 4 more days achieved daily troughs above EC50 in > 50% subjects. These doses are higher than recommended for malaria chemoprophylaxis, and clinical trials are needed to establish safety and efficacy.
Aspergillus Infections Thompson, 3rd, George R; Young, Jo-Anne H
The New England journal of medicine,
2021-Oct-14, Letnik:
385, Številka:
16
Journal Article
It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or ...special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.
This document updates and expands the initial Infectious Diseases Society of America (IDSA) Fever and Neutropenia Guideline that was published in 1997 and first updated in 2002. It is intended as a ...guide for the use of antimicrobial agents in managing patients with cancer who experience chemotherapy-induced fever and neutropenia.
Recent advances in antimicrobial drug development and technology, clinical trial results, and extensive clinical experience have informed the approaches and recommendations herein. Because the previous iteration of this guideline in 2002, we have a developed a clearer definition of which populations of patients with cancer may benefit most from antibiotic, antifungal, and antiviral prophylaxis. Furthermore, categorizing neutropenic patients as being at high risk or low risk for infection according to presenting signs and symptoms, underlying cancer, type of therapy, and medical comorbidities has become essential to the treatment algorithm. Risk stratification is a recommended starting point for managing patients with fever and neutropenia. In addition, earlier detection of invasive fungal infections has led to debate regarding optimal use of empirical or preemptive antifungal therapy, although algorithms are still evolving.
What has not changed is the indication for immediate empirical antibiotic therapy. It remains true that all patients who present with fever and neutropenia should be treated swiftly and broadly with antibiotics to treat both gram-positive and gram-negative pathogens.
Finally, we note that all Panel members are from institutions in the United States or Canada; thus, these guidelines were developed in the context of North American practices. Some recommendations may not be as applicable outside of North America, in areas where differences in available antibiotics, in the predominant pathogens, and/or in health care–associated economic conditions exist. Regardless of venue, clinical vigilance and immediate treatment are the universal keys to managing neutropenic patients with fever and/or infection.
Recombinant herpes zoster (HZ) vaccines may be an alternative to the live-attenuated HZ vaccine for immunocompromised individuals. This was a phase 1/2, randomized, observer-blind, placebo-controlled ...study in adults with multiple myeloma, non-Hodgkin lymphoma (B- or T-cell), Hodgkin lymphoma, or acute myeloid leukemia who had undergone autologous hematopoietic stem-cell transplant 50 to 70 days earlier. Subjects (N = 121) were randomized 1:1:1:1 to receive (at months 0, 1, 3) three doses of 50 μg varicella-zoster virus glycoprotein E (gE) adjuvanted with AS01B, 3 doses of gE adjuvanted with AS01E, 1 dose of saline followed by 2 doses of gE/AS01B, or 3 doses of saline. One month after the last dose (6 months after transplant), frequencies of CD4+ T cells expressing ≥2 activation markers after induction with gE and anti-gE antibody concentrations were higher with all gE/AS01 regimens than with saline. Both responses persisted up to 1 year in subjects vaccinated with gE/AS01. Immune responses were higher in the gE/AS01B 3-dose group than in the gE/AS01B 2-dose group but not higher than in the gE/AS01E 3-dose group. One serious adverse event (pneumonia) was considered vaccine related. Both formulations and both schedules were immunogenic and well tolerated in this population. This study was registered at www.clinicaltrials.gov as #NCT00920218.
•HCT recipients have increased susceptibility to herpes zoster, but live-attenuated vaccines are not appropriate for highly immunocompromised people.•An adjuvanted subunit vaccine against herpes zoster elicits strong immune responses with an acceptable safety profile in adult autologous HCT recipients.
Summary Background Available drugs against cytomegalovirus have adverse effects that compromise their prophylactic use in recipients of allogeneic stem-cell transplants. We assessed the safety, ...tolerability, and antiviral activity of oral maribavir in such patients. Methods In this placebo-controlled, randomised, double-blind, multicentre phase 3 study, we enrolled adult patients recipient-seropositive or donor-seropositive for cytomegalovirus who had undergone allogeneic stem-cell transplantation. Patients were recruited from 90 centres in Canada, Europe, and the USA. After engraftment, patients were stratified by recipient cytomegalovirus serostatus and conditioning regimen (myeloablative or reduced-intensity) and assigned (2:1) by masked computer-generated randomisation sequence to receive maribavir 100 mg twice daily or placebo for up to 12 weeks, with weekly blood cytomegalovirus surveillance. If the virus was detected, administration of study drug was stopped and pre-emptive anticytomegalovirus treatment started. The primary endpoint was cytomegalovirus disease within 6 months of transplantation. Analysis was by intention-to-treat. This study is registered with ClinicalTrials.gov , NCT00411645. Findings Between December, 2006, and May, 2008, 681 patients were enrolled and assigned to receive maribavir (454) or placebo (227). The incidence of cytomegalovirus disease within 6 months was 20 of 454 (4%) for the maribavir group and 11 of 227 (5%) for the placebo group (OR 0·90; 95% CI 0·42–1·92). During the 100 days following transplantation, cytomegalovirus infection rates as measured by pp65 antigenaemia were lower in the maribavir group (26·4%) than in the placebo group (34·8%; OR 0·67; 0·47–0·95), but not when measured by plasma cytomegalovirus DNA PCR (27·8% vs 30·4%; OR 0·88; 0·62–1·25), nor by initiation of treatment against cytomegalovirus (30·6% vs 37·4%; OR 0·73, 0·52–1·03). Maribavir was well tolerated: most adverse events, including incident acute graft-versus-host disease and neutropenia, affected both groups equally, except for taste disturbance (15% maribavir, 6% placebo). Interpretation Compared with placebo, maribavir prophylaxis did not prevent cytomegalovirus disease when started after engraftment. Cytomegalovirus disease as a primary endpoint might not be sufficient to show improvements in cytomegalovirus prevention in recipients of allogeneic stem-cell transplants in the setting of pre-emptive antiviral treatment. Clinical and virological composite endpoints should be used in future trials. Funding ViroPharma Incorporated.
Background
Clostridioides difficile infection (CDI) frequently complicates allogeneic hematopoietic stem cell (allo‐HCT) and solid organ transplantation (SOT).
Methods
We retrospectively analyzed ...risk factors and outcomes of CDI occurring within 30 days of transplant.
Results
Between March 2010 and June 2015, 466 allo‐HCT and 1454 SOT were performed. The CDI cumulative incidence (95% CI) was 10% (8–13) and 4% (3–5), following allo‐HCT and SOT, respectively (p < .01), occurring at a median (range) 7.5 days (1–30) and 11 (1–30), respectively (p = .18). In multivariate analysis, fluoroquinolones use within 14 days pre‐transplantation was a risk factor for CDI following allo‐HCT (HR 4.06 95% CI 1.31–12.63, p = .02), and thoracic organ(s) transplantation was a risk factor for CDI following SOT (HR 3.03 95% CI 1.31–6.98) for lung and 3.90 (1.58–9.63) for heart and heart/kidney transplant, p = .02. Compared with no‐CDI patients, the length of stay (LOS) was prolonged in both allo‐HCT (35 days 19–141 vs. 29 13–164, p < .01) and SOT with CDI (16.5 4–101 vs. 7 0–159, p < .01), though not directly attributed to CDI. In allo‐HCT, severe acute graft‐versus‐host disease (aGVHD) occurred more frequently in patients with CDI (33.3% vs. 15.8% without CDI, p = .01) and most aGVHD (87.5%) followed CDI. Non‐relapse mortality or overall survival, not attributed to CDI, were also similar in both allo‐HCT and SOT.
Conclusions
Early post‐transplant CDI is frequent, associated with fluoroquinolones use in allo‐HCT and the transplanted organ in SOT, and is associated with longer LOS in both the groups without difference in survival but with increased aGVHD in allo‐HCT.
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