Invasive Aspergillosis in Liver Transplant Recipients in The Current Era.

Invasive aspergillosis (IA) is a rare but fatal disease among liver transplant recipients (LiTRs). We performed a multi-center 1:2 case-control study comparing LiTRs diagnosed with proven/probable IA and controls with no invasive fungal infection. We included 62 IA cases and 124 matched controls. Disseminated infection occurred only in eight cases (13%). 12-week all-cause mortality of IA was 37%. In multivariate analyses, systemic antibiotics usage (adjusted odds ratio [aOR], 4.74; p=0.03) and history of pneumonia (aOR, 48.7; p=0.01) were identified as independent risk factors associated with the occurrence of IA. Moreover, reoperation (aOR, 5.99; p=0.01), systemic antibiotics usage (aOR, 5.03; p=0.04), and anti-mold prophylaxis (aOR, 11.9; p=0.02) were identified as independent risk factors associated with the occurrence of early IA. Among IA cases, Aspergillus colonization (adjusted hazard ration [aHR], 86.9; p<0.001), ICU stay (aHR, 3.67; p=0.02), disseminated IA (aHR, 8.98; p<0.001), and dialysis (aHR, 2.93; p=0.001) were identified as independent risk factors associated with 12-week all-cause mortality; while recent receipt of tacrolimus (aHR, 0.11; p=0.001) was protective. Mortality among LiTRs with IA remains high in the current era. The identified risk factors and protective factors may be useful for establishing robust targeted anti-mold prophylactic and appropriate treatment strategies against IA.

Experience with dalbavancin for long-term antimicrobial suppression of left ventricular assist device infections.

BACKGROUND: Left ventricular assist devices (LVAD) are a common strategy for management of end-stage heart failure. LVADs carry a risk of infection of the implanted device components, and skin flora are commonly implicated. Long-term antibiotics may be needed for management of deep device infection or recurrent superficial infections. In appropriately selected patients, dalbavancin can be a feasible option given its extended dosing interval. METHODS: This is a retrospective, single-center review of patients presenting with an LVAD infection between January 2011 and November 2022, where management included the use of dalbavancin. Data regarding LVAD placement, details of index infection, dalbavancin use and outcomes was obtained from chart review, and documented in a RedCap database. RESULTS: The mean time from LVAD placement to index infection was 131.6 weeks (standard deviation 87.2 weeks). The most common targeted organism was Corynebacterium striatum in six of 10 patients. Index infection presented as deep driveline infection in four patients and recurrent superficial driveline infection in three patients. Five patients had a concurrent bloodstream infection. Dalbavancin was discontinued in two patients due to breakthrough infection, with one patient requiring surgical intervention. No drug-related adverse events were noted. CONCLUSION: Dalbavancin is an attractive option in the management of long-term LVAD infection in patients for whom alternative oral or parenteral antibiotics are not a feasible option. Additional studies are needed to determine the optimal dosing of dalbavancin in this setting, and to study adverse events and long-term outcomes of dalbavancin.

The role of microbiome-based therapeutics for the reduction and prevention of antimicrobial-resistant organism colonization.

The gut is host to a diverse array of microbiota that constitute a complex ecological system crucial to human physiology. Disruptors to the normal host microbiota, such as antimicrobials, can cause a loss of species diversity in the gut, reducing its ability to resist colonization by invading pathogens and potentially leading to colonization with antimicrobial resistant organisms (AROs). ARO negatively impact gut health by disrupting the usual heterogeneity of gut microbiota and have the potential to cause systemic disease. In recent years, fecal microbiota transplantation (FMT) has been increasingly explored in the management of specific disease states such as Clostridioides difficile infection (CDI). Promising data from management of CDI has led to considerable interest in understanding the role of therapeutics to restore the gut microbiota to a healthy state. This review aims to discuss key studies that highlight the current landscape, and explore existing clinical evidence, for the use of FMT and microbiome-based therapeutics in combating intestinal colonization with ARO. We also explore potential future directions of such therapeutics and discuss unaddressed needs in this field that merit further investigation.

Future prospects of therapeutic clinical trials in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a markedly heterogeneous hematological malignancy that is most commonly seen in elderly adults. The response to current therapies to AML is quite variable, and very few new drugs have been recently approved for use in AML. This review aims to discuss the issues with current trial design for AML therapies, including trial end points, patient enrollment, cost of drug discovery and patient heterogeneity. We also discuss the future directions in AML therapeutics, including intensification of conventional therapy and new drug delivery mechanisms; targeted agents, including epigenetic therapies, cell cycle regulators, hypomethylating agents and chimeric antigen receptor T-cell therapy; and detail of the possible agents that may be incorporated into the treatment of AML in the future.

Herpes Zoster During Immunosuppressive Therapy For Autoimmune Diseases.

BACKGROUND: Patients on immunosuppressive therapy are at a greater risk for herpes zoster reactivation and are more likely to have adverse outcomes. Propylactic antivrials and vaccinations may potentially prevent these complications. METHODS: Medical literature addressing the clinical course and therapy of herpes zoster in patients receiving immunosuppressive therapy for autoimmune disorders, and the roles of anti-viral prophylaxis and vaccination was reviewed. Research databases including PubMed, Ovid, Medline, Google Scholar and Cochrane were utilized. RESULTS: Acyclovir and its derivatives are most commonly used in this setting for treatment and reduction of post-zoster complications. Foscarnet may be used for acyclovir-resistant strains. At both conventional and ultralow doses, acyclovir has proven effective when used as prophylaxis, reducing the incidence of zoster and its complications in immunosuppressed patients. Additionally, ultra-low doses are associated with significantly reduced side effects. The zoster vaccine, Zostavax, a live-attenuated vaccine has shown promising results in several clinical trials. However, live-attenuated vaccines should be cautiously used in immunosuppressed patients. For patients who require immunosuppressive therapy, vaccination 2-3 months prior to therapy may be appropriate. CONCLUSIONS: Prophylactic antiviral therapy and vaccination help significantly reduce morbidity and mortality from zoster reactivation in patients receiving immunosuppressive therapy.

Incidence and Mortality of COVID-19-Associated Invasive Fungal Infections Among Critically Ill Intubated Patients: A Multicenter Retrospective Cohort Analysis.

Background: An association between coronavirus disease 2019 (COVID-19)-associated invasive fungal infections (CAIFIs) and high mortality among intubated patients has been suggested in previous research. However, some of the current evidence was derived from small case series and multicenter studies conducted during different waves of the COVID-19 pandemic. We examined the incidence of CAIFIs and their associated mortality using a large, multicenter COVID-19 database built throughout the pandemic. Methods: We conducted a retrospective analysis of the National COVID Cohort Collaborative (N3C) database collected from 76 medical centers in the United States between January 2020 and August 2022. Patients were 18 years or older and intubated after severe acute respiratory syndrome coronavirus 2 infection. The primary outcomes were incidence and all-cause mortality at 90 days. To assess all-cause mortality, we fitted Cox proportional hazard models after adjusting for confounders via inverse probability weighting. Results: Out of the 4 916 229 patients with COVID-19 diagnosed during the study period, 68 383 (1.4%) met our cohort definition. The overall incidence of CAIFI was 2.80% (n = 1934/68 383). Aspergillus (48.2%; n = 933/1934) and Candida (41.0%; n = 793/1934) were the most common causative organisms. The incidence of CAIFIs associated with Aspergillus among patients who underwent BAL was 6.2% (n = 83/1328). Following inverse probability weighting, CAIFIs caused by Aspergillus (hazard ratio [HR], 2.0; 95% CI, 1.8-2.2) and Candida (HR, 1.7; 95% CI, 1.5-1.9) were associated with increased all-cause mortality. Systemic antifungals reduced mortality in 17% of patients with CAIFI with Aspergillus and 24% of patients with CAIFI with Candida. Conclusions: The incidence of CAIFI was modest but associated with higher 90-day all-cause mortality among intubated patients. Systemic antifungals modified mortality.

Assessment of the characteristics of COVID-19 infection among healthcare personnel working in long-term care facilities.

Between May and June 2021, healthcare personnel at two long-term care facilities underwent SARS-CoV-2 anti-nucleocapsid immunoglobulin G testing and completed a survey on COVID-19 exposures and symptoms. Antibody positivity rate was 8.9%. Similar rates of COVID-19 exposure occurred in non-occupational and occupational settings, with high self-reported adherence to workplace infection prevention practices.

Beyond a team: The comprehensive interdisciplinary endocarditis program in the United States.

Although multidisciplinary teams have been shown to decrease in-hospital mortality for patient with infectious endocarditis, most studies have focused on the inpatient role of these teams, and are primarily based at European tertiary care centers. There is limited literature available on the optimal longitudinal care of this patient population. Here we outline our experience developing an interdisciplinary endocarditis program at the University of Kentucky, which cares for patients from their index hospitalization into the outpatient setting, while also coordinating transfers from regional hospitals and offering education to regional providers.

Incidence, predictors, and 30-day outcomes of Clostridioides difficile infection in patients undergoing cystectomy: A national database analysis.

Clostridioides difficile infection (CDI) is the second most common health care acquired infection (HAI) and the most common gastrointestinal HAI, with an estimated 365,200 cases reported by the center for disease control in 2017. CDI continues to remain a major cause of inpatient admission and utilization of health care resources. This study aimed to determine the true incidence, risk factors, and outcomes of CDI in patients undergoing cystectomy. We conducted an analysis of patients undergoing cystectomy between 2015 and 2017 using the American college of surgeon National Surgical Quality Improvement Program to study the incidence, risk factors, and 30 day postsurgical outcomes associated with CDI following cystectomy. Developed by the American College of Surgery, this is a nationally validated, risk adjusted, and outcomes based program designed to determine and improve the quality of surgical and postsurgical care. The incidence of CDI following cystectomy was 3.6% in our patient cohort. About 18.8% of patients developed CDI following hospital discharge. None elective surgeries and complete cystectomy procedures had a higher rate of CDI. About 48.4% of patients with CDI had a preceding postoperative infection. Postoperative organ space infections, postoperative renal failure, postoperative sepsis, and septic shock were independently associated with the development of CDI, (all P < 0.05). Patients who developed postoperative CDI during hospitalization had lengthier hospital admissions than those who did not develop a CDI and had a higher risk of deep venous thrombosis formation. A sizable number of patients experience CDIs after cystectomy procedures in the USA, and CDI development is associated with an increase in length of stay and unplanned readmissions. Interventions and initiatives are needed to reduce this burden of disease.

Knowledge, beliefs, and practices related to coronavirus disease 2019 (COVID-19) infection and vaccination in healthcare personnel working at nonacute care facilities.

OBJECTIVE: To characterize experiences, beliefs, and perceptions of risk related to coronavirus disease 2019 (COVID-19), infection prevention practices, and COVID-19 vaccination among healthcare personnel (HCP) at nonacute care facilities. DESIGN: Anonymous survey. SETTING: Three non-acute-care facilities in St. Louis, Missouri. PARTICIPANTS: In total, 156 HCP responded to the survey, for a 25.6% participation rate). Among them, 32% had direct patient-care roles. METHODS: Anonymous surveys were distributed between April-May 2021. Data were collected on demographics, work experience, COVID-19 exposure, knowledge, and beliefs about infection prevention, personal protective equipment (PPE) use, COVID-19 vaccination, and the impact of COVID-19. RESULTS: Nearly all respondents reported adequate knowledge of how to protect oneself from COVID-19 at work (97%) and had access to adequate PPE supplies (95%). Many HCP reported that wearing a mask or face shield made communication difficult (59%), that they had taken on additional responsibilities due to staff shortages (56%), and that their job became more stressful because of COVID-19 (53%). Moreover, 28% had considered quitting their job. Most respondents (78%) had received at least 1 dose of COVID-19 vaccine. Common reasons for vaccination were a desire to protect family and friends (84%) and a desire to stop the spread of COVID-19 (82%). Potential side effects and/or inadequate vaccine testing were cited as the most common concerns by unvaccinated HCP. CONCLUSIONS: A significant proportion of HCP reported increased stress and responsibilities at work due to COVID-19. The majority were vaccinated. Improving workplace policies related to mental health resources and sick leave, maintaining access to PPE, and ensuring clear communication of PPE requirements may improve workplace stress and burnout.

Delays in lumbar puncture are independently associated with mortality in cryptococcal meningitis: a nationwide study.

BACKGROUND: Cryptococcal meningitis (CM) is the most serious presentation of invasive cryptococcosis. Seen in patients with and without HIV infection, CM is associated with significant morbidity and mortality. Early lumbar puncture is a cornerstone of treatment in cryptococcal meningitis. We present findings from a nationwide analysis of patients admitted with CM in the United States between 2007 and 2016, with the aim of determining the impact of delays in lumbar puncture on inpatient outcomes. METHODS: The national inpatient sample (NIS) database was queried for all inpatient visits for cryptococcal meningitis between January 2007 and December 2016. Logistic regression models were used to determine risk factors for inpatient mortality, prolonged admissions, and delays in obtaining an initial lumbar puncture. RESULTS: The annual number of admissions for CM decreased during the study interval, from 3590 in 2007 to 2830 in 2016. Mortality did not change over this period (9.9%); however, length of stay and inpatient cost significantly increased. The proportion of patients with HIV declined from 70.7% to 54.0%. Delay in lumbar puncture beyond the first 24 h was independently associated with mortality (OR = 1.55, CI = 1.31-1.82, p-value <.001). Patients admitted on a weekend, those of African-American ethnicity, and those without a known history of HIV were more likely to have delays in obtaining an early LP. HIV patients had a lower risk of mortality (OR = 0.77, CI = 0.68-0.86, p-value <.001). CONCLUSION: We found an independent association of delay in early lumbar puncture with worsened patient outcomes. Inpatient mortality for patients with CM continues to remain high, with an increasing proportion of patients without underlying HIV infection. There were significant deviations in management of CM from Infectious Diseases Society of America (IDSA) guidelines.

Overview of the Mutational Landscape in Primary Myelofibrosis and Advances in Novel Therapeutics.

Primary Myelofibrosis is a BCR-ABL negative myeloproliferative neoplasm with a variety of hematological presentations, including thrombosis, bleeding diathesis and marrow fibrosis. It is estimated to have an incidence of 1.5 per 100,000 people each year. Although JAK2 or MPL mutations are seen in PMF, several other mutations have recently been documented, including mutations in CALR, epigenetic regulators like TET, ASXL1, and 13q deletions. The identification of these mutations has improved the ability to develop novel treatment options. These include JAK inhibitors like ruxolitinib, heat shock protein-90 inhibitors like ganetespib, histone deacetylase inhibitors including panobinostat, pracinostat, vorinostat and givinostat, hypomethylating agents like decitabine, hedgehog inhibitors like glasdegib, PI3K, AKT and mTOR inhibitors like everolimus as well as telomerase inhibitors like imtelstat. Research on novel therapeutic options is being actively pursued in order to expand treatment options for primary myelofibrosis however currently, there is no curative therapy other than allogenic hematopoietic stem cell transplantation (ASCT) which is possible in select patients.