Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation.

INTRODUCTION: Fungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB. PATIENTS AND METHODS: Patients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB. RESULTS: Both regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05). DISCUSSION: These results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy.

A population-based analysis of attributable hospitalisation costs of invasive fungal diseases in haematological malignancy patients using data linkage of state-wide registry and costing databases: 2009-2015.

BACKGROUND: Invasive fungal diseases (IFD) are associated with significant treatment-related costs in patients with haematological malignancies (HM). OBJECTIVES: The objectives of this study were to characterise the gross and attributable hospitalisation costs of a variety of IFD in patients with HM by linking state-wide hospital administrative and costing datasets. PATIENTS/METHODS: We linked the Victorian Admitted Episodes Dataset, Victorian Cancer Registry and the Victorian Cost Data Collection from 1 July 2009 to 30 June 2015. IFD cases and uninfected controls were matched 1:1 based on age within ten years, same underlying HM and length of stay prior to IFD diagnosis. The cost difference between surviving cases and controls, indexed to 2019 Australian dollars (AUD) calculated twelve months from IFD diagnosis, was determined using Poisson and negative binomial regression (NBR). RESULTS: From 334 matched pairs, the gross hospitalisation cost of cases was AUD$67 277 compared to AUD$51 158 among uninfected controls, associated with an excess median hospitalisation cost of AUD$16 119 (P < .001) attributable to IFD, approximating to USD$11 362 and €10 154 at purchasing power parity. Median attributable costs were highest for patients with invasive aspergillosis (AUD$55 642; P < .001) and mucormycosis (AUD$51 272; P = .043) followed by invasive candidiasis AUD$24 572 (P < .001). No change in median excess attributable costs was observed over the study period (P = .90) Analyses by NBR revealed a 1.36-fold increase (P < .001) in total hospitalisation costs among cases as compared to controls twelve months from IFD diagnosis. CONCLUSION: Invasive aspergillosis and mucormycosis have high attributable hospitalisation costs but the overall excess IFD cost of AUD$16 119 is modest, potentially reflecting missed or miscoded fungal episodes arguing for better quality surveillance data at hospital level.

Superficial mycoses in Belgium: Burden, costs and antifungal drugs consumption.

BACKGROUND: Monitoring of superficial mycoses requires more attention due to their important incidence, health costs and antifungal drugs consumption. OBJECTIVES: The objectives were to estimate the burden of superficial mycoses in Belgium and to assess trends in associated antifungal consumption. METHODS: The burden of dermatophytoses (including onychomycosis), as well as skin and genital candidiasis, was estimated using disability-adjusted life years (DALY). Moreover, trends in systemic and topical antifungal consumption in ambulatory care were examined for the period 2010-2017, together with their associated costs. RESULTS: Due to their high incidence and long treatment duration, dermatophytoses represented the bulk of the burden, accounting for 92.2% of the total DALYs of superficial mycoses. Terbinafine was the most prescribed antifungal in terms of doses (35.4% of the total doses) while fluconazole was the most delivered drug in terms of packages (29.1% of the total packages). More than 70% of the prescriptions were made by general practitioners while consumption varied according to age and gender of the patients. A global 12% decrease in antifungal prescriptions was observed between 2011 and 2017. However, this reduction would result mainly from packaging changes and increased self-medication. A significant decrease in itraconazole treatments was notably compensated by an increased prescription of fluconazole packages. CONCLUSION: This study emphasises that dermatological presentations of superficial mycoses are the most important in terms of both burden and antifungal consumption in Belgium. Further reduction in antifungals use can be achieved by applying the adequate treatment after identification of the causative agent.

Estimation of Direct Healthcare Costs of Fungal Diseases in the United States.

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.

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis.

Invasive fungal infections (IFIs) are associated with high mortality rates and large economic burdens. Triazole prophylaxis is used for at-risk patients with hematological malignancies or stem cell transplants. We evaluated both the efficacy and the cost-effectiveness of triazole prophylaxis. A network meta-analysis (NMA) of randomized controlled trials (RCTs) evaluating fluconazole, itraconazole capsule and solution, posaconazole, and voriconazole was conducted. The outcomes of interest included the incidences of IFIs and deaths. This was coupled with a cost-effectiveness analysis from patient perspective over a lifetime horizon. Probabilities of transitions between health states were derived from the NMA. Resource use and costs were obtained from the Singapore health care institution. Data on 5,505 participants in 21 RCTs were included. Other than itraconazole capsule, all triazole antifungals were effective in reducing IFIs. Posaconazole was better than fluconazole (odds ratio [OR], 0.35 [95% confidence interval [CI], 0.16 to 0.73]) and itraconazole capsule (OR, 0.25 [95% CI, 0.06 to 0.97]), but not voriconazole (OR, 1.31 [95% CI, 0.43 to 4.01]), in preventing IFIs. Posaconazole significantly reduced all-cause deaths, compared to placebo, fluconazole, and itraconazole solution (OR, 0.49 to 0.54 [95% CI, 0.28 to 0.88]). The incremental cost-effectiveness ratio for itraconazole solution was lower than that for posaconazole (Singapore dollars [SGD] 12,546 versus SGD 26,817 per IFI avoided and SGD 5,844 versus SGD 12,423 per LY saved) for transplant patients. For leukemia patients, itraconazole solution was the dominant strategy. Voriconazole was dominated by posaconazole. All triazole antifungals except itraconazole capsule were effective in preventing IFIs. Posaconazole was more efficacious in reducing IFIs and all-cause deaths than were fluconazole and itraconazole. Both itraconazole solution and posaconazole were cost-effective in the Singapore health care setting.

Analysis of the efficiency and costs of antifungal prophylaxis and mycological diagnostics in patients undergoing allogeneic haematopoietic cell transplantation: "real life" evaluation.

Antifungal prophylaxis/therapy (AP/AT) raises the cost of allogeneic haematopoietic cell transplantation (alloHCT). Its efficacy, different approaches for AP/AT, diagnostic measures and cost-effectiveness must still be evaluated. In 2010, we conducted a prospective study with 106 consecutive patients receiving an alloHCT analysing AP/AT, choice and costs of diagnostics applied including CT scans, galactomannan (Gal) and ß-D-glucan (ß-D) testing. Antifungal prophylaxis in 91 patients consisted of fluconazole (FLU) or L-AMB (AmBisome™ 1 or 3 mg/kg/day b.w.), and antifungal therapy had to be initiated in 38 % of the FLU/L-AMB-1-mg patients but in none with L-AMB 3 mg. Empirical AT consisted of L-AMB 1 mg/kg (n = 12) and preemptive AT of L-AMB 3 mg/kg (n = 17) and proved very efficacious with no further antifungal drug escalation in 89.6 %. Mean costs of diagnostic measures were 402 €/alloHCT; however, only 22 % of the CT scans, 4 % of ß-D and 3 % of galactomannan testing were positive. We detected one proven, 17 probable and 14 possible fungal infections. Due to the German diagnosis-related group system with additional compensation, all our AP/AT strategies were adequately reimbursed. While clinical symptoms and CT scans are the most commonly used, inexpensive decision-making tools for starting AT, the expensive laboratory diagnostic procedures are ineffective; we have therefore discontinued regular GAL/ß-D testing and changed our AP in patients at risk.

The burden of serious human fungal infections in Brazil.

In Brazil, human fungal infections are prevalent, however, these conditions are not officially reportable diseases. To estimate the burden of serious fungal diseases in 1 year in Brazil, based on available data and published literature. Historical official data from fungal diseases were collected from Brazilian Unified Health System Informatics Department (DATASUS). For fungal diseases for which no official data were available, assumptions of frequencies were made by estimating based on published literature. The incidence (/1000) of hospital admissions for coccidioidomycosis was 7.12; for histoplasmosis, 2.19; and for paracoccidioidomycosis, 7.99. The estimated number of cryptococcal meningoencephalitis cases was 6832. Also, there were 4115 cases of Pneumocystis pneumonia in AIDS patients per year, 1 010 465 aspergillosis and 2 981 416 cases of serious Candida infections, including invasive and non-invasive diseases. In this study, we demonstrate that more than 3.8 million individuals in Brazil may be suffering from serious fungal infections, mostly patients with malignant cancers, transplant recipients, asthma, previous tuberculosis, HIV infection and those living in endemic areas for truly pathogenic fungi. The scientific community and the governmental agencies should work in close collaboration in order to reduce the burden of such complex, difficult-to-diagnose and hard to treat diseases.

Burden of serious fungal infections in Belgium.

We aimed to estimate the total number of serious fungal infections occurring yearly in Belgium. The number of cryptococcal infections was retrieved from the National Reference Center for Mycosis. Populations at risk and fungal infections frequencies in these populations were used to estimate incidence or prevalence of other fungal infections. The Belgian population consists of 11.10 million people. Cryptococcal meningitis is rare. In all, 15 of the 1227 newly diagnosed HIV/AIDS cases presented with Pneumocystis jirovecii pneumonia. This accounts for ±14% of total PCP cases (n = 120). The incidence of candidaemia is estimated as 5/100,000 resulting in 555 cases and 213 deaths. A total number of 675 invasive aspergillosis cases and ≥169 deaths attributed to this infection were calculated. Chronic pulmonary aspergillosis is estimated to be prevalent in 662 cases. Allergic bronchopulmonary aspergillosis cases were estimated to be 23,119 applying a 2.5% and 15% rate in adult asthma and cystic fibrosis patients respectively. Severe asthma with fungal sensitisation cases was estimated to be 30,402. There were 174,760 women with recurrent Candida vaginitis assuming a 6% rate in women aged between 15 and 50. Approximately 233,000 people of the Belgian population (2.1%) are estimated to suffer from a fungal infection on a yearly basis.

Burden of serious fungal infections in the Czech Republic.

We have estimated the number of serious fungal infections in the Czech Republic. All published epidemiology papers reporting Czech fungal infection rates were identified. Where no data existed, we used specific populations at risk and fungal infection frequencies in those populations. Population statistics were obtained from the 2011 Census data, prevalence and incidence data for at-risk conditions were obtained from publicly accessible healthcare statistics and relevant surveys. We estimate that 152,840 Czech women suffer with recurrent vaginal thrush. Allergic bronchopulmonary aspergillosis is likely in 4739 adults and 6581 more have severe asthma with fungal sensitisation. Hypersensitivity pneumonitits secondary to fungi is estimated in 1050 cases and 365 people may have chronic pulmonary aspergillosis. Oesophageal candidiasis is estimated in 210 HIV-positive people. There are 12 cases of Pneumocystis pneumonia in HIV population and 60 more cases in non-HIV population. There are an estimated 526 cases of candidaemia, 79 cases of Candida peritonitis and 297 cases of invasive aspergillosis a year. About 176,000 (1.67%) Czech people suffer from severe fungal infections each year, predominantly from recurrent vaginitis and allergic respiratory conditions. Substantial uncertainty surrounds these estimates except for invasive aspergillosis in haematology and candidaemia in critical care.

Pharmacoeconomic evaluation of voriconazole vs. liposomal amphotericin B in empiric treatment of invasive fungal infections in Turkey.

BACKGROUND: Invasive fungal infections (IFI) are associated with considerable expense and mortality on healthcare systems. There is a need to provide evidence of both clinical efficacy and value for money with any health technology. The current pharmacoeconomic evaluation investigated the use of liposomal amphotericin B (LAmB) and voriconazole for the empiric treatment of IFI in the Turkish setting. METHODS: Decision analytic modelling was used to create a pathway for patient treatment with a 5-point composite outcome measure. The data was obtained from a major non-inferiority multicentre randomised controlled study, with an expert panel of clinicians in Turkey providing transition probabilities and cost not available in the literature. Sensitivity analyses were performed on the inputs from the clinical trial and the expert panel. RESULTS: As per the base case analysis, voriconazole was preferred by Turkish Lira (TL) 2,523 per patient treated and TL2,520 per surviving patient. LAmB was the preferred alternative by TL5,362 per successfully treated patient. Removing fever resolution as part of the composite outcome measure resulted in voriconazole being the preferred alternative per successfully treated patient. Univariate sensitivity analysis highlighted that increasing the duration of voriconazole by >1.2 days or decreasing LAmB by >1.0 days changes the result. Monte Carlo Simulation resulted in 69.4% of simulations favouring voriconazole per patient treated. CONCLUSION: There is a strong likelihood that voriconazole is economically more favourable than LAmB in the empiric treatment of IFI in Turkey.

The case for antifungal stewardship.

PURPOSE OF REVIEW: Antimicrobial stewardship (AMS) has overwhelmingly focussed on antibiotics while antifungal agents have been largely neglected despite the few published audits of antifungal drug use demonstrating clear deficiencies in prescribing behaviour. In this review, we outline not only the elements of antifungal stewardship (AFS) in common with AMS but also features specific to antifungal drugs, combined with insights from our experience in AFS. RECENT FINDINGS: Invasive fungal diseases (IFDs) have a lower institutional incidence relative to infections caused by multiresistant bacteria, but their health and economic burden are substantial. Pharmacy costs inclusive of antifungal agents are a major determinant of IFD-attributable hospital cost. High drug costs and the toxicities of antifungal agents are the principal rationale for AFS while antifungal resistance is an emerging but less prevalent issue. The high mortality/morbidity associated with IFDs, including adverse impact on curative chemotherapy, combined with suboptimal diagnostic tools, has driven the overuse of antifungal drugs. De-escalation of empiric therapy is one of the most challenging aspects of AFS to implement. Nonculture-based tests may enhance AFS, but refinement of both target populations and clinical pathways incorporating their use is required. Performance indicators including structural, process and outcome measures are integral for demonstrating the value of AFS programmes. SUMMARY: Practice guidelines adapted to the local context are the cornerstone of AFS. Local epidemiology informs the choice of antifungal agents for the prevention and management of IFDs, underscoring the need for surveillance. Adherence to minimum standards of prescribing ensures that clinical outcomes are optimized and drug toxicities minimized, thus meeting healthcare quality and safety goals.

Hospital costs, length of stay and mortality attributable to invasive scedosporiosis in haematology patients.

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.

Posaconazole prophylaxis during front-line chemotherapy of acute myeloid leukemia: a single-center, real-life experience.

BACKGROUND: Posaconazole is effective as primary antifungal prophylaxis of invasive fungal diseases in patients with acute myeloid leukemia. DESIGN AND METHODS: The impact of primary antifungal prophylaxis administered during front-line chemotherapy for acute myeloid leukemia was evaluated by comparing 58 patients who received oral amphotericin B (control group) to 99 patients who received oral posaconazole (posaconazole group). The primary endpoint was the incidence of proven/probable invasive fungal diseases. Secondary endpoints included incidence of invasive aspergillosis, survival at 4 and 12 months after the diagnosis of acute myeloid leukemia and costs. RESULTS: Proven/probable invasive fungal diseases were documented in 51.7% of patients in the control group and in 23.2% in the posaconazole group (P=0.0002). Invasive aspergillosis was documented in 43% of patients in the control group and in 15% in the posaconazole group (P=0.002). No survival difference was observed in patients aged over 60 years. In patients aged 60 years or less, a statistically significant survival advantage was observed at 4 months, but no longer at 12 months, in the posaconazole group (P=0.03). It was calculated that in the posaconazole group there was a mean 50% cost reduction for the antifungal drugs. CONCLUSIONS: Primary antifungal prophylaxis with posaconazole during front-line chemotherapy was effective in preventing invasive fungal diseases in a "real-life" scenario of patients with acute myeloid leukemia, resulted in an early but transitory survival advantage in younger patients and was economically advantageous.

Treatment cost of invasive fungal disease (Ifd) in patients with acute myelogenous leukaemia (Aml) or myelodysplastic syndrome (Mds) in German hospitals.

Invasive fungal disease (IFD) causes increasing morbidity and mortality in haematological cancer patients. Reliable cost data for treating IFD in German hospitals is not available. Objective of the study was to determine the institutional cost of treating the IFD. Data were obtained by retrospective chart review in German hospitals. Patients had either newly diagnosed or relapsed acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Direct medical cost was calculated from hospital provider's perspective. A total of 108 patients were enrolled at 5 tertiary care hospitals, 36 IFD patients and 72 controls. The vast majority of IFD patients (74%) were diagnosed with invasive aspergillosis. On average, the hospital stay for IFD patients was 12 days longer than in control patients. All patients in the IFD group and 89% of patients in the control group received antifungal drugs. Mean direct costs per patient were €51,517 in the IFD group and €30,454 in the control group. Incremental costs of €21,063 were dominated by cost for antifungal drugs (36%), hospital stay (32%) and blood products (23%). From the perspective of hospitals in Germany the economic burden of IFD in patients with AML or MDS is substantial. Therefore, prevention of IFD is necessary with respect to both clinical and economic reasons.

Attributable hospital cost and antifungal treatment of invasive fungal diseases in high-risk hematology patients: an economic modeling approach.

Studies using patient-level data to determine the attributable cost of invasive fungal diseases (IFDs) are few. Using a case-control study with activity-based costing of patients admitted to a quaternary hospital from 2002 to 2007, we determined attributable hospitalization cost (and 12 weeks thereafter), length of stay (LOS), and costly antifungal treatment (C-AT; liposomal amphotericin B, voriconazole, posaconazole, caspofungin), expressed as defined daily doses (DDDs) per IFD episode, in patients with hematological malignancies and hematopoietic stem cell recipients. Matching criteria and median regression modeling controlled for confounding variables, including LOS prior to IFD onset. Multiple mycoses were identified in 43 matched case-control pairs (n=86). A separate sensitivity analysis included 22 unmatched patients. IFD status was associated with a median excess cost of AU$30,957 (95% confidence interval [CI]=AU$2,368 to AU$59,546; P=0.034), approximating at purchasing power parity US$21,203 (95% CI=US$1,622 to US$40,784) and €15,788 (95% CI=€1,208 to €30,368), increasing to AU$80,291 (95% CI=AU$33,636 to AU$126,946; P=0.001), i.e., US$54,993 (95% CI=US$23,038 to US$86,948) and €40,948 (95% CI=€17,154 to €64,742), with intensive care unit (ICU) requirement. Cost determinants were pharmacy costs (64%; P<0.001) inclusive of antifungal treatment (27%; P<0.001) and ward costs (27%; P=0.091), with proportions persisting through 12 weeks for 25 surviving matched pairs (pharmacy, 60% [P=0.12]; ward, 31% [P=0.21]). Median LOS was not significantly increased unless unmatched patients were included (8 days, 95% CI=1.8 to 14 days; P=0.012). Excess C-ATs were 17 DDDs (95% CI=15 to 19 DDDs; P<0.001) per case patient and 19 DDDs (95% CI=16 to 22 DDDs; P<0.001) per ICU patient. The sensitivity analysis was confirmatory (for median cost, AU$29,441, 95% CI=AU$5,571 to AU$53,310, P=0.016; for C-AT, 17 DDDs, 95% CI=16 to 18 DDDs, P<0.001). IFD results in increased hospital and ICU costs, with pharmacy costs, including antifungal treatment, being major determinants. Consumption of costly antifungal drugs may be a novel resource metric with wider generalizability than cost alone.

[Cost effectiveness of posaconazole versus fluconazole/itraconazole in the prophylactic treatment of invasive fungal infections in Mexico]. / Costo efectividad de posaconazol versus fluconazol/itraconazol en el tratamiento profiláctico de las infecciones fúngicas invasivas en México.

UNLABELLED: Cost effectiveness of posaconazole versus fluconazole/itraconazole therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. OBJECTIVE: To estimate the cost effectiveness and long-term combined effects of Posaconazole versus fluconazole/itraconazole (standard azole) therapy in the prophylaxis against invasive fungal Infections among high-risk neutropenic patients in Mexico. METHODS: A previously validated Markov model was used to compare the projected lifetime costs and effects of two theoretical groups of patients, one receiving Posaconazole and the other receiving standard azole. The model estimates total costs, numbers of IFIs, and QALY per patient in each prophylaxis group. To extrapolate trial results to a lifetime horizon, the model was extended with one-month Markov cycles in which mortality risk is specific to the underlying disease. Data on the probabilities of IFI were obtained from Study Protocol PO1899. Drug costs were taken from average wholesale drug reports for 2009. Cost and health effects were discounted at 5% according to the Mexican guideline. The analysis was conducted from the Mexican healthcare perspective using 2008 unit cost prices. RESULTS: Our model projects an accumulated cost to the Mexican healthcare system per patient receiving the Posaconazol regimen of $US 5,634 compared to $US 7,463 for the standard azole regimen. The accumulated discounted effect is 3.13 LY or 2.25 QALYs per patient receiving Posaconazol, compared to 2.96 LY or 2.13 QALYs per patient receiving standard azole. Posaconazol remained the dominant strategy across each scenario. Probabilistic sensitivity analysis tested numerous assumptions about the model cost and efficacy parameters and found that the results were robust to most changes. CONCLUSION: Posaconazole provides modest incremental benefits compared with standard azole therapy in the prophylaxis against IFIs among high-risk neutropenic patients. Routine Posaconazole use appears a cost saving when the likelihood of IFIs or the cost of treatment medications is high.

Medical cost analysis for antifungal prophylaxis in neutropenic patients with hematological malignancies: a systematic simulation analysis.

GOALS OF WORK: We assessed the medical costs of different antifungal agents for prophylaxis of invasive fungal infections in neutropenic patients in Japan with a cost simulation model designed for the study. PATIENTS AND METHODS: We used probabilities of prophylaxis failure, possible cases for empiric therapy, probable proportions of infections caused by fungus species among prophylaxis failure patients, and incidence of adverse events caused by any reason, based on systematic analysis of previously reported randomized trials identified by a computerized search of the PubMed database. Antifungal agents were limited to oral fluconazole, oral itraconazole, micafungin, and liposomal amphotericin B. The range of the expected medical cost was simulated as a sensitivity analysis using 95% of confidence interval of a mean. MAIN RESULTS: Fifteen studies were identified for our analysis. The prophylactic efficacy was comparable between the four agents. The simulated expected cost for invasive fungal infection prophylaxis and treatment of the infection was $1,035.74 when oral itraconazole was used for prophylaxis, $1,552.81 with oral fluconazole, $2,245.96 with micafungin, and $3,028.10 with liposomal amphotericin B. The total cost including treatment cost for adverse events related to each drug was $2,742.14, $3,547.91, $3,034.57, and $3,028.10, respectively. This result was confirmed in a sensitivity analysis in which IFI incidence and therapy duration were tested as parameters. CONCLUSIONS: Our analysis results suggest that oral itraconazole is the most cost-effective prophylactic antifungal agent for invasive fungal infections in neutropenic patients with hematological malignancies, and this result was robust by sensitivity analysis.

Posaconazole versus fluconazole or itraconazole for prevention of invasive fungal infections in patients undergoing intensive cytotoxic therapy for acute myeloid leukemia or myelodysplasia: a cost effectiveness analysis.

INTRODUCTION: Invasive fungal infections (IFI) remain a clinical concern in hematological patients with prolonged neutropenia because they are a major cause of morbidity and mortality. In a recent randomized trial, prophylaxis with posaconazole was associated with fewer IFI and related deaths relative to a fluconazole or itraconazole (Flu/Itra) control group (p < 0.001). In the current study, a cost effectiveness analysis was conducted to estimate the economic value of posaconazole as an alternative to Flu/Itra when used to prevent IFI in this patient population. METHODS: A decision analysis model was developed using clinical and economic data from randomized comparative trials, the economic literature, and from expert opinion. The data were then used to estimate the incremental cost per life year saved with oral posaconazole prophylaxis relative to Flu/Itra from the Canadian provincial health care system perspective. The base case results were then tested with a sensitivity analysis which evaluated extremes in the incidence of IFI as well as variations in their cost of management. RESULTS: Prophylaxis with posaconazole provides increased efficacy and an overall cost savings of approximately $Can4,259 per patient. Despite variations in the base case parameters, the sensitivity analysis suggested stability in the primary findings. Posaconazole was associated with an overall cost savings (range = $Can1,765 to $Can4,505) in all of the scenarios evaluated. Optimal cost effectiveness was obtained because the drug was able to avoid the more resource intensive Aspergillus infections. CONCLUSIONS: Prophylaxis with posaconazole in cancer patients with prolonged neutropenia is not only cost effective but also cost saving. The economic benefits were due to the drug's ability to reduce the incidence of high cost fungal infections, particularly Aspergillus species.

The disease and economic burden of neutropenic fever in adult patients in Australian cancer treatment centres 2008: analysis of the Victorian Admitted Episodes Dataset.

BACKGROUND: Although the incidence of neutropenic fever (FN) is estimated to be up to 80% for some malignancies, the epidemiological characteristics and economic burden are not well understood for Australian patients. AIMS: To describe underlying malignant conditions, potential aetiologies, clinical outcomes and healthcare utilization for an Australian population with FN, and to estimate the economic burden of this condition within the Australian healthcare sector. METHODS: Epidemiological features of FN were extracted from a population-based hospital morbidity dataset, the Victorian Admitted Episodes Dataset (VAED), for a 12-month period (2008). These were analysed according for a range of malignancy categories. Economic burden of hospitalizations was estimated according to data presented in the Round 12 National Hospital Cost Data Collection Report. RESULTS: A total of 2599 admitted episodes across 92 Victorian hospitals fulfilled inclusion criteria for FN. Metropolitan hospitalizations accounted for 79% episodes. FN illness comprised underlying solid tumours diagnoses (40%), followed by leukaemia (29.3%), lymphoma (22%) and myeloma (8.5%). Length of hospital stay was >15 days for approximately one-third of hospitalizations. intensive care unit admission rates were 5.9-11.7%. Weighted average costs of hospitalization (AUD) for solid tumours, lymphoma, myeloma and leukaemia were $8309 ± $391, 18,145 ± $1602, $21,764 ± $1289 and $22,596 ± $2618 respectively. CONCLUSIONS: Using VAED indices, epidemiological features of Australian patients with FN appear comparable with international reports. In contrast to US data, estimated healthcare costs are up to 50% lower in the Australian healthcare sector. These data offer important insights for prioritizing of research agendas and resource allocation.

Assessing the cost of an invasive forest pathogen: a case study with oak wilt.

Economic assessment of damage caused by invasive alien species provides useful information to consider when determining whether management programs should be established, modified, or discontinued. We estimate the baseline economic damage from an invasive alien pathogen, Ceratocystis fagacearum, a fungus that causes oak wilt, which is a significant disease of oaks (Quercus spp.) in the central United States. We focus on Anoka County, Minnesota, a 1,156 km(2) mostly urban county in the Minneapolis-Saint Paul metropolitan region. We develop a landscape-level model of oak wilt spread that accounts for underground and overland pathogen transmission. We predict the economic damage of tree mortality from oak wilt spread in the absence of management during the period 2007-2016. Our metric of economic damage is removal cost, which is one component of the total economic loss from tree mortality. We estimate that Anoka County has 5.92 million oak trees and 885 active oak wilt pockets covering 5.47 km(2) in 2007. The likelihood that landowners remove infected oaks varies by land use and ranges from 86% on developed land to 57% on forest land. Over the next decade, depending on the rates of oak wilt pocket establishment and expansion, 76-266 thousand trees will be infected with discounted removal cost of $18-60 million. Although our predictions of removal costs are substantial, they are lower bounds on the total economic loss from tree mortality because we do not estimate economic losses from reduced services and increased hazards. Our predictions suggest that there are significant economic benefits, in terms of damage reduction, from preventing new pocket establishment or slowing the radial growth of existing pockets.