The pathogenesis of device-associated infections is related to biofilm bacteria that exhibit distinct characteristics with respect to growth rate, structural features, and protection from host immune ...mechanisms and antimicrobial agents when compared with planktonic counterparts. Biofilm-associated infections are prevented, diagnosed, and treated differently from infections not associated with biofilms. This article reviews innovative concepts for the prevention of biofilm formation, and novel treatment approaches. Specific approaches for the diagnosis and prevention of catheter-associated urinary tract and bloodstream infections, as well as infections associated with orthopedic implants and cardiovascular implantable electronic devices, are also discussed.
Purpose of Review
Antifungal stewardship has been recognized as a significant component of any antimicrobial stewardship program. In this article, we aim to provide a review of recommendations and ...antifungal stewardship interventions in hematologic patients.
Recent Findings
Core elements of antibiotic stewardship programs can be applied to antifungal stewardship practices. Engagement of high-prescribing specialists, timely access to fungal diagnostics, screening for drug-drug interactions, and therapeutic drug monitoring are recommended practices that specifically pertain to antifungal stewardship. Tools recently developed in assessing adherence to guidelines can prove useful in evaluating prescribing practices. The most common longitudinal metrics are likely to hinge on measuring antifungal consumption. However, many of the parameters to measure antifungal stewardship activity and performance are extremely challenging to obtain.
Summary
A multifaceted antifungal stewardship approach is required to improve antifungal use among hematologic patients in an efficient and sustainable manner.
Understanding temporal dynamics of COVID-19 symptoms could provide fine-grained resolution to guide clinical decision-making. Here, we use deep neural networks over an institution-wide platform for ...the augmented curation of clinical notes from 77,167 patients subjected to COVID-19 PCR testing. By contrasting Electronic Health Record (EHR)-derived symptoms of COVID-19-positive (COVID
; n = 2,317) versus COVID-19-negative (COVID
; n = 74,850) patients for the week preceding the PCR testing date, we identify anosmia/dysgeusia (27.1-fold), fever/chills (2.6-fold), respiratory difficulty (2.2-fold), cough (2.2-fold), myalgia/arthralgia (2-fold), and diarrhea (1.4-fold) as significantly amplified in COVID
over COVID
patients. The combination of cough and fever/chills has 4.2-fold amplification in COVID
patients during the week prior to PCR testing, in addition to anosmia/dysgeusia, constitutes the earliest EHR-derived signature of COVID-19. This study introduces an
platform for the real-time synthesis of institutional biomedical knowledge. The platform holds tremendous potential for scaling up curation throughput, thus enabling EHR-powered early disease diagnosis.
COVID-19 patients show heterogeneity in clinical presentation and outcomes that makes pandemic control and strategy difficult; optimizing management requires a systems biology approach of ...understanding the disease. Here we sought to potentially understand and infer complex disease progression, immune regulation, and symptoms in patients infected with coronaviruses (35 SARS-CoV and 3 SARS-CoV-2 patients and 57 samples) at two different disease progression stages. Further, we compared coronavirus data with healthy individuals (n = 16) and patients with other infections (n = 144; all publicly available data). We applied inferential statistics (the COVID-engine platform) to RNA profiles (from limited number of samples) derived from peripheral blood mononuclear cells (PBMCs). Compared to healthy individuals, a subset of integrated blood-based gene profiles (signatures) distinguished acute-like (mimicking coronavirus-infected patients with prolonged hospitalization) from recovering-like patients. These signatures also hierarchically represented multiple (at the system level) parameters associated with PBMC including dysregulated cytokines, genes, pathways, networks of pathways/concepts, immune status, and cell types. Proof-of-principle observations included PBMC-based increases in cytokine storm-associated IL6, enhanced innate immunity (macrophages and neutrophils), and lower adaptive T and B cell immunity in patients with acute-like disease compared to those with recovery-like disease. Patients in the recovery-like stage showed significantly enhanced TNF, IFN-γ, anti-viral, HLA-DQA1, and HLA-F gene expression and cytolytic activity, and reduced pro-viral gene expression compared to those in the acute-like stage in PBMC. Besides, our analysis revealed overlapping genes associated with potential comorbidities (associated diabetes) and disease-like conditions (associated with thromboembolism, pneumonia, lung disease, and septicemia). Overall, our COVID-engine inferential statistics platform and study involving PBMC-based RNA profiling may help understand complex and variable system-wide responses displayed by coronavirus-infected patients with further validation.
The role of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) convalescent plasma in the treatment of Coronavirus Disease 2019 (COVID-19) in immunosuppressed individuals remains ...controversial. We describe the course of COVID-19 in patients who had received anti-CD20 therapy within the 3 years prior to infection. We compared outcomes between those treated with and those not treated with high titer SARS-CoV2 convalescent plasma. We identified 144 adults treated at Mayo clinic sites who had received anti-CD20 therapies within a median of 5.9 months prior to the COVID-19 index date. About one-third (34.7%) were hospitalized within 14 days and nearly half (47.9%) within 90 days. COVID-19 directed therapy included anti-spike monoclonal antibodies (n = 30, 20.8%), and, among those hospitalized within 14 days (n = 50), remdesivir (n = 45, 90.0%), glucocorticoids (n = 36, 72.0%) and convalescent plasma (n = 24, 48.0%). The duration from receipt of last dose of anti-CD20 therapy did not correlate with outcomes. The overall 90-day mortality rate was 14.7%. Administration of convalescent plasma within 14 days of the COVID-19 diagnosis was not significantly associated with any study outcome. Further study of COVID-19 in CD20-depleted individuals is needed focusing on the early administration of new and potentially combination antiviral agents, associated or not with vaccine-boosted convalescent plasma.
Purpose of review
To discuss the approach to antifungal prophylaxis and treatment for invasive aspergillosis in immunocompromised patients with hematologic malignancies, hematopoietic stem cell ...transplant, and solid organ transplant recipients.
Recent findings
Primary prophylaxis against
Aspergillus
is recommended for patients with acute myelogenous leukemia receiving remission-induction chemotherapy. Posaconazole or voriconazole are appropriate antifungal agents. A new formulation of itraconazole (SUBA-itraconazole) is an alternative option. Breakthrough infections on isavuconazole prophylaxis have been recently reported. For liver transplant recipients, targeted prophylaxis is recommended in the presence of certain risk factors.
Voriconazole and isavuconazole are the preferred agents for the treatment of invasive aspergillosis. Isavuconazole, a novel extended-spectrum triazole with activity against
Aspergillus
and
Mucorales
, was found to be non-inferior compared to voriconazole. Combination of voriconazole with an echinocandin is generally not recommended. Reduction in immunosuppression is recommended as part of the management of invasive aspergillosis. The adjunctive use of interferon-γ may be considered in patients with severe or refractory disease, although a benefit has not been clearly demonstrated.
Summary
The approach to prevention and treatment of invasive aspergillosis has evolved along with changes in immunosuppressive treatment and introduction of novel antifungal agents.
For cellulitis that does not respond to conventional antimicrobial treatment, clinicians should consider, among other explanations, several noninfectious disorders that might masquerade as infectious ...cellulitis. Diseases that commonly masquerade as this condition include thrombophlebitis, contact dermatitis, insect stings, drug reactions, eosinophilic cellulitis (the Wells syndrome), gouty arthritis, carcinoma erysipelatoides, familial Mediterranean fever, and foreign-body reactions. Diseases that uncommonly masquerade as infectious cellulitis include urticaria, lymphedema, lupus erythematosus, sarcoidosis, lymphoma, leukemia, Paget disease, and panniculitis. Clinicians should do an initial diagnostic work-up directed by the findings from a detailed history and complete physical examination. In many cases, skin biopsy is the only tool that helps identify the correct diagnosis. Special tests may also be needed.
Enterococcus faecalis can cause healthcare-associated biofilm infections, including those of orthopedic devices. Treatment of enterococcal prosthetic joint infection is difficult, in part, due to ...biofilm-associated antimicrobial resistance. We previously showed that the E. faecalis OG1RF genes ahrC and eep are in vitro biofilm determinants and virulence factors in animal models of endocarditis and catheter-associated urinary tract infection. In this study, we evaluated the role of these genes in a rat acute foreign body osteomyelitis model and in in vitro biofilm-associated antimicrobial resistance. Osteomyelitis was established for one week following the implantation of stainless steel orthopedic wires inoculated with E. faecalis strains OG1RF, ΩahrC, and ∆eep into the proximal tibiae of rats. The median bacterial loads recovered from bones and wires did not differ significantly between the strains at multiple inoculum concentrations. We hypothesize that factors present at the infection site that affect biofilm formation, such as the presence or absence of shear force, may account for the differences in attenuation in the various animal models we have used to study the ΩahrC and ∆eep strains. No differences among the three strains were observed in the planktonic and biofilm antimicrobial susceptibilities to ampicillin, vancomycin, daptomycin, linezolid, and tetracycline. These findings suggest that neither ahrC nor eep directly contribute to E. faecalis biofilm-associated antimicrobial resistance. Notably, the experimental evidence that the biofilm attachment mutant ΩahrC displays biofilm-associated antimicrobial resistance suggests that surface colonization alone is sufficient for E. faecalis cells to acquire the biofilm antimicrobial resistance phenotype.
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