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Background: Fungal diseases range from relatively-minor superficial and mucosal infections to severe, life-threatening systemic infections. Delayed diagnosis and treatment can lead to poor patient outcomes and high medical costs. The overall burden of fungal diseases in the United States is challenging to quantify, because they are likely substantially underdiagnosed., Methods: To estimate the total, national, direct medical costs associated with fungal diseases from a healthcare payer perspective, we used insurance claims data from the Truven Health MarketScan 2014 Research Databases, combined with hospital discharge data from the 2014 Healthcare Cost and Utilization Project National Inpatient Sample and outpatient visit data from the 2005-2014 National Ambulatory Medical Care Survey and the National Hospital Ambulatory Medical Care Survey. All costs were adjusted to 2017 dollars., Results: We estimate that fungal diseases cost more than $7.2 billion in 2017, including $4.5 billion from 75055 hospitalizations and $2.6 billion from 8993230 outpatient visits. Hospitalizations for Candida infections (n = 26735, total cost $1.4 billion) and Aspergillus infections (n = 14820, total cost $1.2 billion) accounted for the highest total hospitalization costs of any disease. Over half of outpatient visits were for dermatophyte infections (4981444 visits, total cost $802 million), and 3639037 visits occurred for non-invasive candidiasis (total cost $1.6 billion)., Conclusions: Fungal diseases impose a considerable economic burden on the healthcare system. Our results likely underestimate their true costs, because they are underdiagnosed. More comprehensive estimates of the public health impact of these diseases are needed to improve their recognition, prevention, diagnosis, and treatment., (Published by Oxford University Press for the Infectious Diseases Society of America 2018.)

Purpose: The cost-effectiveness of voriconazole versus fluconazole prophylaxis against fungal infections in hematopoietic cell transplant (HCT) recipients is investigated., Methods: A decision-analytic model was developed to estimate the drug costs associated with planned or supplemental prophylaxis and empirical therapy and the costs of treating suspected or documented invasive fungal infections (IFIs) in HCT recipients. Published clinical trial data on 599 patients who received 100-180 days of prophylactic therapy with voriconazole or fluconazole were used to model specified IFI-prevention and mortality outcomes; 6-month, 12-month, and lifetime incremental cost-effectiveness ratios (ICERs) were estimated, with a bootstrap analysis performed to reffect the uncertainty of the clinical trial data., Results: Estimated mean total prophylaxis and IFI-related costs associated with voriconazole versus fluconazole prophylaxis over 12 months were higher in the entire study population and among patients receiving HCT for diagnoses other than acute myeloid leukemia (AML) but were not significantly different for patients with AML. The cost per IFI avoided ($66,919) and the cost per life-year gained ($5,453) were lower among patients with AML who received voriconazole relative to the full study population. ICERs were more favorable for voriconazole over a 6-month time frame and when modeling was conducted using generic price data. Assuming a threshold value of $50,000 for one year of life gained, the calculated probability of voriconazole being cost-effective was 33% for the full study population and 85% for the AML subgroup., Conclusion: The decision model indicated that voriconazole prophylaxis was cost-effective for patients undergoing allogeneic HCT for AML.

Background: Scedosporium species are increasingly recognized as a cause of invasive mould disease in haematology patients, but little is known about the hospitalization costs and outcomes attributable to invasive scedosporiosis (SCEDO)., Methods: A retrospective case-control study was undertaken during 2002-10 to determine the attributable inpatient costs, length of stay (LOS) and mortality associated with SCEDO in haematology patients. Case patients with SCEDO (n = 30) were matched 1 : 2 to controls (n = 60) according to haematological diagnosis, admission year and age. Diagnostics, antifungal drugs, ward and other SCEDO-related costs were estimated using actual cost data. Median regression modelling was used to adjust for variables that were not accounted for in the matched-pairs analysis., Results: The crude total median cost of treating SCEDO was AU$32 182 per patient versus AU$17 424 per control. In multivariable analysis, SCEDO was associated with median excess costs of AU$23 611 (95% CI = AU$17 992-AU$29 231; P < 0.001), approximating US$15 509 at purchasing power parity, with prolonged LOS of 13 days (95% CI = 8.2-17.8 days; P < 0.001). Exclusion of cases and matched pairs with early death further increased the median excess cost and LOS. The cost differential was driven by ward costs (64%, P = 0.005) and antifungal treatment costs (29%, P < 0.001). The all-cause inpatient mortality was 38 times higher for the SCEDO cases versus the control group (63.3% versus 1.7%; P < 0.001)., Conclusions: SCEDO has substantial impact on hospital resource consumption, LOS and mortality in haematology patients. Risk factors and preventative measures for SCEDO should be further studied.

Purpose: The results of a pharmacoeconomic study of the cost-effectiveness of posaconazole versus fluconazole in preventing invasive fungal infections (IFIs) in patients with graft-versus-host disease (GVHD) are reported., Methods: The results of a randomized clinical trial suggested that posaconazole may be as effective as fluconazole for the prevention of IFIs in recipients of allogeneic cell transplants who develop severe GVHD and that posaconazole may be superior to fluconazole in reducing IFI-related deaths. Using published data from that trial and data from secondary sources, an economic model was developed to estimate the costs, IFIs avoided, and life-years saved with posaconazole versus fluconazole therapy. The results of the modeled 112-day treatment simulation were extrapolated to a lifetime horizon., Results: In the modeled simulation, posaconazole therapy was associated with a lower probability of IFI development (0.05 versus 0.09), increased discounted life-years (7.87 life-years versus 7.66 life-years), and higher discounted costs per patient ($8,860 versus $5,710 in 2006 U.S. dollars) relative to fluconazole therapy. The estimated incremental cost-effectiveness of posaconazole versus fluconazole for IFI prophylaxis was $85,300 per IFI avoided and $15,300 per life-year saved. A sensitivity analysis indicated a 90% probability that the use of posaconazole for this purpose would be cost-effective at a threshold of $50,000 per life-year saved., Conclusion: Posaconazole is in the range of currently accepted criteria for cost- effectiveness relative to fluconazole for the prevention of IFIs among patients with GVHD.

Purpose: Drug costs and utilization after implementation of a posaconazole prophylaxis protocol in adults with acute myelogenous leukemia (AML) were studied., Methods: Adult patients who initiated induction or reinduction chemotherapy for the treatment of AML between December 1, 2006, and March 31, 2008, at a tertiary care hospital were included in this retrospective cohort study. Patients were divided into two groups: preprotocol (treated before June 1, 2007) and postprotocol (treated on or after June 1, 2007). Medical charts, including pharmacy and laboratory data, were reviewed for all patients. Outcomes measured included antifungal and antibacterial drug costs and utilization and total pharmacy costs., Results: A total of 66 patients were evaluated (33 in each group). Baseline characteristics, except patient age, were similar between groups. Each group incurred similar costs and utilized resources for similar periods of time as evidenced by similar lengths of stay, duration of neutropenia, and mortality. Antibacterial costs, total pharmacy costs, and other utilization outcomes were also similar between the two groups. Alterations to antifungal management strategy occurred more often in the postprotocol group (33% versus 58%, p = 0.048)., Conclusion: Implementation of a posaconazole protocol did not significantly alter antifungal or antibacterial drug costs or utilization or total pharmacy costs. Prophylactic posaconazole was frequently changed to alternative antifungal therapy due to an adverse drug event, perceived lack of efficacy, avoidance of a drug interaction, or inability to tolerate oral intake.

Purpose: The mortality, length of hospitalization, and costs associated with invasive fungal infections (IFIs) in hospitalized patients were studied., Methods: This retrospective database study used data from the 2004 Healthcare Cost and Utilization Project Nationwide In-patient Sample. Patients were selected for inclusion based on diagnostic codes corresponding to an IFI. A control group was matched to the IFI group based on high-risk conditions (i.e., cancer, infection with human immunodeficiency virus, chronic obstructive pulmonary disease, diabetes mellitus, and solid-organ, hematopoietic stem cell, or bone marrow transplant), age, sex, and hospital region and teaching status. Excess mortality, length of hospital stay, and costs were estimated as the differences between the IFI and control groups., Results: A total of 11,881 patients were identified with a discharge diagnosis of an IFI who could be matched to a control. Frequent infections included candidiasis (40.2%), other mycoses (36.3%), and aspergillosis (16.4%). Patients with IFIs had a significantly higher mortality rate (15% versus 5%), mean +/- S.E. length of stay (18.7 +/- 0.4 days versus 7.3 +/- 0.1 days), and mean +/- S.E. costs ($44,726 +/- $1,255 versus $15,445 +/- $404) (p < 0.001 for all comparisons) than did patients without IFIs. The burden of IFIs varied by high-risk condition (highest for transplant recipients and patients with cancer) and type of infection (highest for candidiasis, zygomycosis, and aspergillosis)., Conclusion: Examination of a large database showed that, compared with high-risk patients without IFIs, those with IFIs had higher mortality, a longer hospital stay, and higher costs associated with their hospitalization.

Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count > 0.5 x 10(9)/L, toxicity precluding further fluconazole use, and death. By Kaplan-Meier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018). The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01).

Intravascular (IV) catheter sepsis is a widely recognized complication of IV therapy or monitoring, but little emphasis has been placed on the morbidity and cost associated with this infection. To assess the consequences of IV catheter sepsis, we examined the medical records of 94 patients with 102 episodes of IV catheter sepsis due to percutaneously inserted catheters. Major complications occurred in 33 (32%) of the episodes and included septic shock (12 episodes), sustained sepsis (12), suppurative thrombophlebitis (7), metastatic infection (5), endocarditis (2), and arteritis (2). One patient died due to sepsis, and hospital stay was clearly prolonged in 15 episodes. The risk of major complications was highest in episodes of IV catheter sepsis caused by Candida, Pseudomonas aeruginosa, Staphylococcus aureus, or multiple pathogens, and the most severe complications were usually caused by S. aureus. The hospital cost of IV catheter sepsis was assessed by reviewing medical and billing records to identify extra medical care and then multiplying charges for that care by the appropriate cost-to-charge ratio. The average cost per episode, adjusted to 1991 dollars, was $3,707 for all episodes and $6,064 for episodes caused by S. aureus. The morbidity and cost associated with IV catheter sepsis warrant substantial efforts to minimize the incidence of this complication and especially to prevent cases due to S. aureus.