Hospital-treated serious and invasive aspergillosis and candidiasis infections during the COVID-19 pandemic: a retrospective analysis of Hospital Episode Statistics data from England.

OBJECTIVES: To investigate the impact of COVID-19 on the burden of hospital-treated Aspergillus and Candida infections in England. DESIGN: A retrospective study using Hospital Episodes Statistics data to estimate the burden of serious and invasive fungal infections (SIFIs) in all patients admitted in England during March 2018-February 2020 (pre-COVID-19) and during March 2020-October 2021 (the COVID-19 period). SETTING: Hospitals in England. POPULATION: All patients with codes corresponding to serious and invasive aspergillosis and candidiasis in any diagnosis position during their admission pre-COVID-19 and during the COVID-19 period. OUTCOME MEASURES: Age, spells, patient counts, mean length of stay, admission to critical care unit (CCU), length of stay in CCU, 30-day readmissions, failed discharges (readmission within 7 days) and comorbidities. RESULTS: During the COVID-19 period, hospitalisation spells with an invasive candidiasis code fell by 3.2% and spells with an aspergillosis code by 24.8%. Mean length of stay was higher for patients with aspergillosis with or without COVID-19 and candidiasis with or without COVID-19 during the pandemic than before the pandemic. During the pandemic, mean length of stay was higher for patients with aspergillosis with COVID-19 than those with aspergillosis alone but slightly lower for patients with candidiasis with COVID-19 than for those with candidiasis alone. Of patients with a diagnosis of COVID-19, 52.5% with aspergillosis and 60.0% with candidiasis were treated in CCU compared with 13.2% and 37.1%, respectively, without a COVID-19 diagnosis. The percentage of 30-day readmissions and failed discharges for patients with SIFI was higher for those with COVID-19 than for those without. CONCLUSIONS: The burden of aspergillosis and candidiasis has been affected by COVID-19. Aspergillosis diagnoses fell among hospitalised patients during the pandemic, while candidiasis continued to fluctuate in patterns similar to pre-COVID-19. A higher burden for patients with SIFI was observed, whether or not they also had a diagnosis of COVID-19. Our findings highlight extra considerations and burden on management of serious SIFI as a result of the COVID-19 pandemic.

Using Behavior Change Theory to Identify Drivers and Barriers for Antifungal Treatment Decisions: A Case Study in a Large Teaching Hospital in the East of England, UK.

INTRODUCTION: Antifungal stewardship (AFS) programs are recognized to contribute to optimizing antifungal prescribing for treatment and prophylaxis. However, only a small number of such programs are implemented. Consequently, evidence on behavioral drivers and barriers of such programs and learnings from existing successful AFS programs is limited. This study aimed to leverage a large AFS program in the UK and derive learnings from it. The objective was to (a) investigate the impact of the AFS program on prescribing habits, (a) use a Theoretical Domains Framework (TDF) based on the COM-B (Capability, Opportunity, and Motivation for Behavior) to qualitatively identify drivers and barriers for antifungal prescribing behaviors across multiple specialties, and (c) semiquantitatively investigate trends in antifungal prescribing habits over the last 5 years. METHODS: Qualitative interviews and a semiquantitative online survey were conducted across hematology, intensive care, respiratory, and solid organ transplant clinicians at Cambridge University Hospital. The discussion guide and survey used were developed to identify drivers of prescribing behavior, based on the TDF. RESULTS: Responses were received from 21/25 clinicians. Qualitative outcomes demonstrated that the AFS program was effective in supporting optimal antifungal prescribing practices. We found seven TDF domains influencing antifungal prescribing decisions-five drivers and two barriers. The key driver was collective decision-making among the multidisciplinary team (MDT) while key barriers were lack of access to certain therapies and fungal diagnostic capabilities. Furthermore, over the last 5 years and across specialties, we observed an increasing tendency for prescribing to focus on more targeted rather than broad-spectrum antifungals. CONCLUSIONS: Understanding the basis for linked clinicians' prescribing behaviors for identified drivers and barriers may inform interventions on AFS programs and contribute to consistently improving antifungal prescribing. Collective decision-making among the MDT may be leveraged to improve clinicians' antifungal prescribing. These findings may be generalized across specialty care settings.

The role of diagnostic tests in antifungal stewardship for treating invasive fungal infections: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of an article originally published in the journal Open Forum Infectious Diseases. Invasive fungal infections are caused by fungi. They can spread to deeper parts of the body. Some diagnostic tests are slow and may delay treatment. Better tests help to identify infection early in patients. An antifungal stewardship (shortened to AFS) program is a stepwise process to improve how patients are treated. AFS programs using diagnostic tests may help to manage infections. In this study, researchers wanted to know the impact of such AFS programs. To do so, they looked at the information from 17 previously published studies, which is summarized here. WHAT WERE THE RESULTS?: Infections were identified and treated faster in studies with improved diagnostic tests. Treatment cost decreased when infections were identified and treated early. Patients were treated for shorter periods of time. They also spent less time in hospital. Number of deaths were less. WHAT DO THE RESULTS OF THE STUDY MEAN?: AFS programs based on diagnostic tests helped patients.

Risk factors in people with mold infections that have spread to different parts of the body: a plain language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a summary of a study originally published in ClinicoEconomics and Outcomes Research. Mold infections spread from one to other parts of the body and can infect other body parts. We need to understand what makes people more likely to get this type of mold infection (called invasive mold infection). This summary may help doctors to understand the risks that can relate to invasive mold infections. WHAT WERE THE RESULTS?: The main risks in people with invasive aspergillosis (shortened to IA) and invasive mucormycosis (shortened to IM) were: ○diabetes (high blood sugar and associated conditions), ○lung disease (such as tuberculosis, chronic obstructive pulmonary disorder), ○blood-related cancers (such as leukemia, lymphoma), and ○solid organ transplant (removing an organ from one person and placing in another person). WHAT DO THE RESULTS OF THE STUDY MEAN?: People with the risks listed above may be more likely to get invasive mold infections. People with these risks should talk to their doctor about invasive mold infections. Being aware of these risks may help doctors to be aware of which people are at risk of invasive mold infections.

The Role of Diagnostics-Driven Antifungal Stewardship in the Management of Invasive Fungal Infections: A Systematic Literature Review.

Antifungal stewardship (AFS) programs are key to optimizing antifungal use and improving outcomes in patients with invasive fungal infections. Our systematic literature review evaluated the impact of diagnostics in AFS programs by assessing performance and clinical measures. Most eligible studies were from Europe and the United States (n = 12/17). Diagnostic approaches included serum ß-1-3-D-glucan test (n/N studies, 7/17), galactomannan test (4/17), computed tomography scan (3/17), magnetic resonance (2/17), matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS; 2/17), polymerase chain reaction (1/17), peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) assay (1/17), and other routine methods (9/17). Time to species identification decreased significantly using MALDI-TOF and PNA-FISH (n = 2). Time to targeted therapy and length of empiric therapy also decreased (n = 3). Antifungal consumption decreased by 11.6%-59.0% (7/13). Cost-savings ranged from 13.5% to 50.6% (5/10). Mortality rate (13/16) and length of stay (6/7) also decreased. No negative impact was reported on patient outcomes. Diagnostics-driven interventions can potentially improve AFS measures (antifungal consumption, cost, mortality, and length of stay); therefore, AFS implementation should be encouraged.

Characterizing patients with rare mucormycosis infections using real-world data.

BACKGROUND: Invasive mucormycosis (IM) is a rare and often life-threatening fungal infection, for which clinical and epidemiological understanding is lacking. Electronic health record (EHR) data can be utilized to elucidate large populations of patients with IM to address this unmet need. This study aimed to descriptively assess data on patients with IM using the Optum® EHR dataset. METHODS: US patient data from the Optum® deidentified EHR dataset (2007-2019) were analyzed to identify patients with IM. Patients with hematologic malignancies (HM), at high risk of IM, were selected and sorted by IM diagnosis (ICD9 117.7; ICD10 B46). Demographics, comorbidities/other diagnoses, and treatments were analyzed in patients with IM. RESULTS: In total, 1133 patients with HM and IM were identified. Most were between 40 and 64 years of age, Caucasian, and from the Midwest. Essential primary hypertension (50.31%) was the most common comorbidity. Of the 1133 patients, only 33.72% were prescribed an antifungal treatment. The most common antifungal treatments were fluconazole (24.27%) and posaconazole (16.33%), which may have been prophylactic, and any AmB (15.62%). CONCLUSIONS: A large population of patients with IM were identified, highlighting the potential of analyzing EHR data to investigate epidemiology, diagnosis, and the treatment of apparently rare diseases.

Patient Characteristics and Risk Factors in Invasive Mold Infections: Comparison from a Systematic Review and Database Analysis.

INTRODUCTION: Diagnosis and treatment of invasive mold infections (IMI) can be challenging and IMI is a significant source of morbidity and mortality. Invasive aspergillosis (IA) and invasive mucormycosis (IM) are two of the most common mold infections. A better understanding of patient comorbidities and risk factors that predispose IMI may help clinicians to refine the difficult diagnostic and treatment process. METHODS: A systematic literature review (SLR) was conducted (January 2008-October 2019) for studies reporting comorbidities/risk factors of patients with IA or IM (Phase I), followed by an analysis on the Optum® US EHR database of prominent risk factor cohorts based on SLR findings and expert opinion (Phase II). From the four identified patient cohorts: 1) patients undergoing solid organ transplant (SOT) and patients with 2) hematologic cancers, 3) diabetes, or 4) lung disease, rates of IA, IM, or concurrent IA and IM; patient comorbidities; and Charlson Comorbidity Index (CCI) scores were reported. RESULTS: The SLR included 88 studies, and 46 were used to select comorbidities/risk factors cohorts in IA and IM patients. The most important comorbidities/risk factors in IA and IM patients were diabetes, lung disease, hematological malignances, and SOT. In the Optum database (N=101,340,454 patients), IA rates were highest in lung transplant (10.81%) patients and IM rates were highest in intestine transplant (0.83%) patients, lung transplant (0.43%), and hematopoietic stem cell transplant (0.49%). CCI scores were elevated in all mold infection groups compared to the total Optum cohort. CONCLUSION: The current study describes patient comorbidity and risk factors associated with IA and IM. These data can be used to refine clinical decision-making regarding when to suspect mold infections. Future research should focus on identifying whether patients respond differently to various antifungal treatments to determine if strategic recommendations should be made for certain patient groups.

Health outcomes and economic burden of hospitalized COVID-19 patients in the United States.

OBJECTIVE: The aims of this study were to evaluate health outcomes and the economic burden of hospitalized COVID-19 patients in the United States. METHODS: Hospitalized patients with a primary or secondary discharge diagnosis code for COVID-19 (ICD-10 code U07.1) from 1 April to 31 October 2020 were identified in the Premier Healthcare COVID-19 Database. Patient demographics, hospitalization characteristics, and concomitant medical conditions were assessed. Hospital length of stay (LOS), in-hospital mortality, hospital charges, and hospital costs were evaluated overall and stratified by age groups, insurance types, and 4 COVID-19 disease progression states based on intensive care unit (ICU) and invasive mechanical ventilation (IMV) usage. RESULTS: Of the 173,942 hospitalized COVID-19 patients, the median age was 63 years, 51.0% were male, and 48.5% were covered by Medicare. The most prevalent concomitant medical conditions were cardiovascular disease (73.5%), hypertension (64.8%), diabetes (40.7%), obesity (27.0%), and chronic kidney disease (24.2%). Approximately one-fifth (21.9%) of the hospitalized COVID-19 patients were admitted to the ICU and 16.9% received IMV; most patients (73.6%) did not require ICU admission or IMV, and 12.4% required both. The median hospital LOS was 5 days, in-hospital mortality was 13.6%, median hospital charges were $43,986, and median hospital costs were $12,046. Hospital LOS and in-hospital mortality increased with ICU and/or IMV usage and age; hospital charges and costs increased with ICU and/or IMV usage. Patients with both ICU and IMV usage had the longest median hospital LOS (15 days), highest in-hospital mortality (53.8%), and highest hospital charges ($198,394) and hospital costs ($54,402). LIMITATIONS: This retrospective administrative database analysis relied on coding accuracy and a subset of admissions with validated/reconciled hospital costs. CONCLUSIONS: This study summarizes the severe health outcomes and substantial hospital costs of hospitalized COVID-19 patients in the US. The findings support the urgent need for rapid implementation of effective interventions, including safe and efficacious vaccines.

Contributing Factors to the Clinical and Economic Burden of Patients with Laboratory-Confirmed Carbapenem-Nonsusceptible Gram-Negative Urinary Tract Infections.

PURPOSE: We explored patient- and hospital-level predictor variables for worse clinical and economic outcomes in carbapenem-nonsusceptible urinary tract infections (UTIs). PATIENTS AND METHODS: We used electronic data (January 2013-September 2015; 78 US hospitals) from a large multicenter clinical database. Nonduplicate gram-negative isolates were considered carbapenem-nonsusceptible if they had resistant/intermediate susceptibility. Potential predictors of outcomes (mortality, 30-day readmissions, length of stay [LOS], hospital total cost, and net gain/loss per case) were examined using generalized linear mixed models. Significant predictors were identified based on statistical significance and model goodness-of-fit criteria. RESULTS: A total of 1439 carbapenem-nonsusceptible urine cases were identified. The mortality rate was 5.5%; the hospital readmission rate was 25.0%. Mean (standard deviation [SD]) LOS, total cost, and loss per case were 12 (14) days, $21,502 ($37,172), and $5828 ($26,540), respectively. Hospital-onset (vs community-onset) infection significantly impacted all outcomes: mortality (odds ratio [OR], 2.21; 95% confidence interval [CI], 1.19-4.11; P=.01), 30-day readmissions (OR, 2.35; 95% CI, 1.49-3.71; P<.001), LOS (25.7 vs 10.2 days; P<.001), hospital total cost ($67,810 vs $22,141; P<.001), and loss per case (-$28,054 vs -$10,809; P<.001). Mechanical ventilation/intensive care unit status, neoplasms, and other underlying diseases were also common predictors for worse outcomes overall; polymicrobial infection was significantly associated with worse economic outcomes. Other key predictors were >1 prior hospitalization for 30-day readmissions, high Acute Laboratory Risk of Mortality Score for mortality, LOS, cost, and hospital teaching status for cost. CONCLUSION: Hospital-onset infections, polymicrobial infections, higher clinical severity, and underlying diseases are key predictors for worsened overall burden of carbapenem-nonsusceptible gram-negative UTIs.

Contributing Factors to the Clinical and Economic Burden of Patients with Laboratory-Confirmed Carbapenem-Nonsusceptible Gram-Negative Respiratory Infections.

PURPOSE: This study examined patient- and hospital-level predictor variables that contribute to worse clinical and economic outcomes in patients with carbapenem-nonsusceptible respiratory infections. PATIENTS AND METHODS: Electronic data (January 2013 to September 2015) were from 78 US hospitals. Nonduplicate, gram-negative respiratory isolates were considered carbapenem-nonsusceptible if they tested resistant/intermediate to imipenem, meropenem, doripenem, or ertapenem. Potential predictors of outcomes (in-hospital mortality, 30-day readmission, length of stay [LOS], hospital total cost, and net gain/loss per patient) were examined using univariate analysis and generalized linear mixed models. Statistical significance and model goodness-of-fit criteria were used to identify significant predictors. RESULTS: A total of 1488 carbapenem-nonsusceptible respiratory patients were identified. Overall, the mortality rate was 13.7%, 30-day readmission rate was 20.6%, mean LOS was 20 days, mean total cost was $54,158, and mean net loss was $139 per patient. Our models showed that hospital-onset infection, higher clinical severity, mechanical ventilation/intensive care unit status, polymicrobial infection, and underlying diseases were all significant predictors for mortality, LOS, and total cost. Hospital-onset infections were also associated with a significantly greater net loss (P≤.01), and underlying disease significantly impacted readmissions (P=.03). The number of prior admissions, hospital characteristics, and payer type were also found to significantly impact measured outcomes. CONCLUSION: Carbapenem-nonsusceptible respiratory infections are associated with a considerable clinical and economic burden. The impact of hospital-onset infections on both clinical and economic outcomes highlights the continued need for action on this modifiable risk factor through antimicrobial stewardship and optimal therapy, thereby reducing the burden in this patient population.

Health-care utilization and outcomes of patients at high risk of invasive fungal infection.

PURPOSE: The objectives of this study were to present trends in posaconazole use over time and describe selected outcomes among patients at high risk of invasive fungal infections (IFIs) by use and type of antifungal medicine. METHODS: A retrospective observational study using data from the Premier Healthcare Database between January 2007 and March 2016 was conducted. Inpatient use of posaconazole by formulation and year is described. Separately, four cohorts of patients at high risk of IFI - those with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), hematopoietic stem-cell transplantation (HSCT), and graft-vs-host disease (GVHD) - but without a diagnosis code for IFI during the index encounter were identified as potential candidates for antifungal prophylaxis. Use of antifungal medication(s) in these patients was categorized. Index length of stay (LOS), index hospital costs, and subsequent inpatient and outpatient encounters with IFI at 30, 60, and 90 days post-index encounter are presented by antifungal group for each cohort. The percentage of patients with inpatient and outpatient encounters with IFI at 90 days post-index encounter was determined for each cohort by year. RESULTS: Use of posaconazole oral suspension increased through 2012, then declined as the tablet formulation became available in 2013. A total of 19,872 AML patients, 12,125 MDS patients, 14,220 HSCT patients, and 5,431 GVHD patients were considered potential candidates for antifungal prophylaxis; however, a large proportion of patients within each cohort (33%-94%) did not receive any antifungal drug during the index hospitalization. Index LOS, hospital costs, and subsequent encounters for IFI varied among cohorts and by antifungal group. Within each cohort, subsequent encounters for IFI at 90 days post-index encounter fluctuated but remained rare across different years. CONCLUSION: Over time and as new posaconazole formulations became available, the frequency of use of each formulation changed. In addition, this study suggested a low rate of potential antifungal prophylaxis in high-risk patients. This is one of the first reports attempting to describe antifungal prophylaxis in a contemporary, large, all-payer, geographically representative hospital database.

An update to the cost-effectiveness of posaconazole vs fluconazole or itraconazole in the prevention of invasive fungal disease among neutropenic patients in the United States.

OBJECTIVES: Posaconazole has shown superior clinical efficacy in the prevention of invasive fungal disease (IFD) among neutropenic patients as well as cost-effectiveness in the US healthcare setting vs fluconazole or itraconazole (FLU/ITRA) based on oral suspension formulations of each therapy. This study aims to provide an update on the cost-effectiveness of posaconazole in the current US healthcare setting to reflect bioequivalent tablet formulations of posaconazole and fluconazole, as well as changes in healthcare and drug costs. METHODS: An existing model was used to assess the cost-effectiveness of posaconazole vs FLU/ITRA in the prevention of IFD among patients with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) and chemotherapy-induced neutropenia. Drug efficacy, mortality related to IFD, and death from other causes were estimated for tablet formulations using data from a randomized clinical trial of oral suspensions based on bioequivalence. IFD treatment costs were updated using the average inflation rate over 8 years (2006-2014) and drug costs were based on 2014 Analysource data. RESULTS: Trial data show a lower IFD probability over 100 days of follow-up with posaconazole compared to standard azole therapy (0.05 vs 0.11). The treatment duration on posaconazole is 29 days compared to 24 days for FLU and 29 days for ITRA. The average cost of prophylaxis is higher in the posaconazole group compared to FLU/ITRA ($4673 vs $353); however, the costs associated with treating the IFD are lower in the posaconazole group compared to FLU/ITRA ($2205 vs $5303). The incremental cost effectiveness ratio of IFD avoided for posaconazole is $18,898 vs FLU/ITRA. CONCLUSIONS: In the current healthcare cost environment where both drug costs and overall IFD treatment costs have increased since 2007, posaconazole tablets are a cost-effective alternative to fluconazole or itraconazole in the prevention of IFD among neutropenic patients with AML and MDS in the US.