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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., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

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., (© 2020 Blackwell Verlag GmbH.)

Purpose: To determine the cost-effectiveness of amphotericin B supplementation, we analyzed both current costs to treat postendothelial keratoplasty (EK) fungal infections and potential costs associated with amphotericin B supplementation., Methods: We collected 19 US cases of post-EK fungal eye infections from the published literature and assessed the associated costs from the literature. A survey of surgeons was also conducted with questions regarding their experiences in managing these infections., Results: We estimated that the costs to diagnose, manage, and treat post-EK fungal keratitis and post-EK fungal endophthalmitis are USD $21,113 and $34,850, respectively. The largest portion of the costs can be attributed to the need for additional surgical management, which is required in 79% of the cases. We estimated the total cost of amphotericin B supplementation to be $44.39 per graft with use of conventional amphotericin B and conservative assumptions regarding supplementation processes. Cost-effectiveness analysis demonstrated that amphotericin B supplementation is cost-effective at $100,000 per quality-adjusted life-year level only if amphotericin B supplementation can prevent more than 69.62% of post-EK fungal infections, assuming the incidence of post-EK fungal infection remains at the level it was between 2012 and 2017., Conclusions: We found that amphotericin B supplementation can be cost-effective under conservative assumptions if it is moderately effective in preventing post-EK fungal infections.

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., (© 2019 Blackwell Verlag GmbH.)

The burden of healthcare-associated infections (HCAIs) has traditionally been measured using clinical and economic outcomes. We conducted semi-structured interviews with 18 patients or their caregivers affected by HCAI caused by multidrug-resistant organisms to better understand the human impact of HCAI. Most patients had misconceptions about HCAI and antimicrobial resistance, leading to strong negative feelings towards HCAIs despite positive views of their healthcare providers. Communication issues across power imbalances need to be addressed to help deal with trauma of HCAIs. A holistic approach to HCAIs incorporating patient perspectives will likely help guide policymakers developing solutions to improve patient outcomes., (Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)

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.)

Competing Interests: The authors have declared that no competing interests exist.

Background: Posaconazole is used for the prophylaxis of invasive fungal disease (IFD). Previous studies have shown it to be cost-effective compared to fluconazole/itraconazole. However, posaconazole has never been economically evaluated in developing countries., Aims: The aim of the present study was to perform a cost-effectiveness analysis of posaconazole compared to fluconazole in public (SUS) and private hospitals (PHS) in Brazil., Methods: A cost-effectiveness simulation was conducted on the basis of a pivotal study on the use of posaconazole in acute myeloid leukemia (AML) patients, adjusting the costs to Brazilian data., Results: A pharmacoeconomic analysis was performed on a hypothetical sample of 100 patients in each drug group. The total cost of posaconazole use alone was USD$ 220,656.31, whereas that for fluconazole was USD$ 83,875.00. Our results showed that patients with IFD remain hospitalized for an additional 12 days, at an average cost of USD$ 850.85 per patient per day. The total money spent by PHS for 100 patients for 100 days was USD$ 342,318.00 for the posaconazole group and USD$ 302,039.00 for the fluconazole group. An analysis of sensitivity (10%) revealed no intergroup difference., Conclusions: In Brazil posaconazole is cost-effective, and should be considered for the prophylaxis of patients with AMD/myelodysplasia (AML/MDS) undergoing chemotherapy., (Copyright © 2018 Asociación Española de Micología. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objectives/hypothesis: Invasive fungal sinusitis is an uncommon entity among children. Early recognition is crucial for facilitating successful treatment with minimal morbidity. The goal of this analysis was to identify patient characteristics associated with high-risk surgical disease through a population-based examination into this rare and deadly disease process., Methods: A retrospective chart review of the 2009 and 2012 Kids' Inpatient Database (KID) was conducted. A series of queries (Fungal infection→immunocompromised diagnosis→sinus procedure) identified 102 patients with likely invasive fungal sinusitis. Outcomes included: species, invasive extension, death, and other clinical characteristics., Results: Patients with leukemia/lymphoma constituted 90.2% of individuals evaluated in this analysis. Nearly a quarter of pediatric patients receiving surgical treatment for invasive fungal sinusitis died during their hospital stay -24.9%. Aspergillus was the most commonly recorded mycotic species. Average hospital stay was 59.3 days, and associated hospital costs averaged $746,299 per stay. Patients 0-5 years old were more likely to have orbital involvement -56.3%. Brain extension was noted in 33.7% of this cohort as well. Mucormycosis was an independent predictor of death (p = 0.03), with an odds ratio of 3.835., Conclusion: To the best of our knowledge, this is the largest pediatric cohort with invasive fungal sinusitis in the literature. Patient demographics, cytology, and disease extension offer predictive information regarding patient outcomes for invasive fungal sinusitis. A high clinical suspicion and early treatment may decrease the lengthy and costly hospitalizations in this population., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To assess the economic impact of urinary tract infections (UTIs) and genital mycotic infections (GMIs) among patients with type 2 diabetes mellitus (T2DM) initiated on canagliflozin., Methods: Administrative claims data from April 2013 through June 2014 MarketScan ® databases were extracted. Adults with ≥1 claim for canagliflozin, T2DM diagnosis, and ≥90 days enrollment before and after canagliflozin initiation were propensity score matched to controls with T2DM initiated on other anti-hyperglycemic agents (AHAs). UTI and GMI healthcare costs were evaluated 90-days post-index and reported as cohort means., Results: Rates of UTI claims 90 days post-index were similar in patients receiving canagliflozin for T2DM (n = 31,257) and matched controls (2.7% vs 2.8%, p = .677). More canagliflozin than control patients had GMI claims (1.2% vs 0.6%, p < .001) and antifungal utilization (5.3% vs 2.6%, p < .001). Mean post-index costs to treat UTIs were lower but not significantly different for canagliflozin patients vs matched controls ($27.61 vs $37.33, p = .150). GMI treatment costs were higher for the canagliflozin cohort ($3.68 vs $2.44, p = .041). Combined costs to treat either UTI and/or GMI averaged $31.29 per patient for the canagliflozin cohort v $39.77 for controls (p = .211). Rates and costs of UTIs and GMIs were higher for females than males, but the canagliflozin vs control trends observed for the overall sample were similar for both sexes. There were no significant cost differences between the canagliflozin and control cohorts among patients aged 18-64. Among patients aged 65 and above, GMI treatment costs were not significantly different, but costs to treat UTIs and either UTI and/or GMI were significantly lower for canagliflozin patients vs controls., Conclusions: In a real-world setting, the costs to payers of treating UTIs and GMIs are generally similar for patients with T2DM initiated on canagliflozin vs other AHAs.

Background: The burden of fungal disease in the UK is unknown. Only limited data are systematically collected. We have estimated the annual burden of invasive and serious fungal disease., Methods: We used several estimation approaches. We searched and assessed published estimates of incidence, prevalence or burden of specific conditions in various high risk groups. Studies with adequate internal and external validity allowed extrapolation to estimate current UK burden. For conditions without adequate published estimates, we sought expert advice., Results: The UK population in 2011 was 63,182,000 with 18% aged under 15 and 16% over 65. The following annual burden estimates were calculated: invasive candidiasis 5142; Candida peritonitis complicating chronic ambulatory peritoneal dialysis 88; Pneumocystis pneumonia 207-587 cases, invasive aspergillosis (IA), excluding critical care patients 2901-2912, and IA in critical care patients 387-1345 patients, <100 cryptococcal meningitis cases. We estimated 178,000 (50,000-250,000) allergic bronchopulmonary aspergillosis cases in people with asthma, and 873 adults and 278 children with cystic fibrosis. Chronic pulmonary aspergillosis is estimated to affect 3600 patients, based on burden estimates post tuberculosis and in sarcoidosis., Conclusions: Uncertainty is intrinsic to most burden estimates due to diagnostic limitations, lack of national surveillance systems, few published studies and methodological limitations. The largest uncertainty surrounds IA in critical care patients. Further research is needed to produce a more robust estimate of total burden., (Copyright © 2016 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Introduction: The treatment of fungal infections in severely ill patients is a clinical and economic challenge worldwide. Liposomal amphotericin B and caspofungin are highly effective antifungal drugs; however, they are very expensive and health systems must select the drug that results in the best clinical outcomes and is economically feasible., Areas Covered: A systematic search was conducted in PubMed, Scopus, Web of Science, Cochrane Library, Health Economic Evaluation Database, and Centre for Review and Dissemination to find complete economic evaluations that directly compared the two treatment strategies. Expert commentary: Because of the high cost, patients in developing countries experience difficulty accessing highly effective treatments. These data can subsidize a decision for an effective antifungal treatment with reduced costs from all perspectives.

Objective: In the phase III SECURE trial, isavuconazole was non-inferior to voriconazole for all-cause mortality for the primary treatment of invasive mold disease (IMD) caused by Aspergillus spp. and other filamentous fungi. This analysis assessed whether hospital resource utilization was different between patients treated with isavuconazole vs voriconazole in SECURE., Methods: The analysis population comprised adults with proven/probable/possible IMD enrolled in SECURE. The primary endpoint was hospital length of stay (LOS) in the overall trial population. Patients were also stratified by estimated glomerular filtration rate-modification of diet in renal disease category (< 60 mL/min/1.73 m(2) [moderate-to-severe impairment] and ≥60 mL/min/1.73 m(2) [mild or no impairment]), body mass index (BMI; <25, ≥25-<30, and ≥30 kg/m(2)), and age (≤45, >45-≤65, and >65 years)., Results: Data from 516 patients (258 per arm) were evaluated. Overall, median LOS was not statistically significantly different between the isavuconazole (15.0 days) and voriconazole (16.0 days; p = 0.607) arms. Median LOS was statistically significantly shorter in patients with moderate-to-severe renal impairment treated with isavuconazole (9.0 days) vs voriconazole (19.0 days; hazard ratio [HR]: 3.44; 95% confidence interval [CI] = 1.51-7.83). Median LOS was shorter, but not significantly, in patients with a BMI ≥30 kg/m(2) (isavuconazole 13.5 days vs voriconazole 22 days; HR = 1.57; 95% CI = 0.70-3.52) or aged >65 years (isavuconazole 15.0 days vs voriconazole 20.0 days; HR = 1.37; 95% CI = 0.87-2.16)., Limitations: As the patient subgroups analyzed were small, sub-group findings should be interpreted with caution in light of the lack of statistical significance for each sub-group-by-treatment interaction., Conclusions: Isavuconazole may reduce hospital LOS in certain subgroups of patients with IMD, especially those with moderate-to-severe renal impairment.

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., (© 2015 Blackwell Verlag GmbH.)

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 β-D-glucan (β-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 β-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/β-D testing and changed our AP in patients at risk.

Background: Invasive fungal disease (IFD) causes significant morbidity and mortality in hematologic malignancy patients with high-risk febrile neutropenia (FN). These patients therefore often receive empirical antifungal therapy. Diagnostic test-guided pre-emptive antifungal therapy has been evaluated as an alternative treatment strategy in these patients., Methods: We conducted an electronic search for literature comparing empirical versus pre-emptive antifungal strategies in FN among adult hematologic malignancy patients. We systematically reviewed 9 studies, including randomized-controlled trials, cohort studies, and feasibility studies. Random and fixed-effect models were used to generate pooled relative risk estimates of IFD detection, IFD-related mortality, overall mortality, and rates and duration of antifungal therapy. Heterogeneity was measured via Cochran's Q test, I2 statistic, and between study τ2. Incorporating these parameters and direct costs of drugs and diagnostic testing, we constructed a comparative costing model for the two strategies. We conducted probabilistic sensitivity analysis on pooled estimates and one-way sensitivity analyses on other key parameters with uncertain estimates., Results: Nine published studies met inclusion criteria. Compared to empirical antifungal therapy, pre-emptive strategies were associated with significantly lower antifungal exposure (RR 0.48, 95% CI 0.27-0.85) and duration without an increase in IFD-related mortality (RR 0.82, 95% CI 0.36-1.87) or overall mortality (RR 0.95, 95% CI 0.46-1.99). The pre-emptive strategy cost $324 less (95% credible interval -$291.88 to $418.65 pre-emptive compared to empirical) than the empirical approach per FN episode. However, the cost difference was influenced by relatively small changes in costs of antifungal therapy and diagnostic testing., Conclusions: Compared to empirical antifungal therapy, pre-emptive antifungal therapy in patients with high-risk FN may decrease antifungal use without increasing mortality. We demonstrate a state of economic equipoise between empirical and diagnostic-directed pre-emptive antifungal treatment strategies, influenced by small changes in cost of antifungal therapy and diagnostic testing, in the current literature. This work emphasizes the need for optimization of existing fungal diagnostic strategies, development of more efficient diagnostic strategies, and less toxic and more cost-effective antifungals.

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., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

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., (© 2015 Blackwell Verlag GmbH.)

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., (© 2015 Blackwell Verlag GmbH.)

Background: Liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) are both indicated for treating invasive fungal infections (IFIs) caused by Aspergillus, Candida and Cryptococcus spp. among patients who are refractory to or intolerant of conventional amphotericin B (CAB). Prior studies have suggested similar efficacies but differences in adverse event (AE) profiles between L-AMB and ABLC., Objective: Our objective was to conduct a cost-minimisation and budget impact analysis for the treatment of IFIs with L-AMB and ABLC in a US hospital setting., Methods: A Microsoft® Excel-based budget impact model was developed to estimate the costs associated with using L-AMB and ABLC for the treatment of adult patients with Aspergillus, Candida and Cryptococcus spp. infections, who are refractory to or intolerant of CAB, during a hospital stay. The model was built from a hospital perspective, and included drug costs of L-AMB and ABLC, and costs for treating drug-related AEs (i.e. nephrotoxicity with/without dialysis, infusion-related reactions, anaphylaxis, hypomagnesaemia and hypokalaemia). Average sales price was used as the drug cost estimate in the base-case analyses. The treatment duration and rates of AEs for L-AMB and ABLC were mainly obtained from a retrospective study of these two drugs in the target population using the Cerner Health Facts data. Treatment costs of AEs were obtained from the publicly available sources. The budget impact ($US, year 2011 values) was evaluated for a hypothetical hospital with 100 administrations where L-AMB and ABLC are used for the treatment of the target population by changing the market share of L-AMB and ABLC from 32/68% to an anticipated market share of 60/40% in the base-case analysis. Sensitivity analyses were conducted by varying drug costs, rates of AEs, costs of AEs and anticipated market shares of L-AMB and ABLC., Results: The estimated per-patient cost per hospital episode associated with L-AMB and ABLC use were $US14,563 and $US16,748, respectively. Cost of AEs accounted for 68.7% of the costs for L-AMB and 85.4% for ABLC. In a hypothetical hospital with 100 annual admissions of patients using these two drugs for IFIs, changing the market shares from 32/68% for L-AMB and ABLC, respectively, to 60/40% yielded a 3.8% cost reduction, which corresponded to an absolute cost savings of $US61,191. Sensitivity analyses indicated that the results were robust to changes in input parameter values in most cases., Conclusions: This study suggests that hospitals can realize cost savings by substituting L-AMB for ABLC in the treatment of IFIs. The cost savings are driven by the lower rates of AEs associated with L-AMB use compared with ABLC.

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.

Invasive fungal infections (IFIs) are a major concern within healthcare systems. This pharmacoeconomic study evaluated the use of caspofungin (CAS) versus liposomal amphotericin B (L-AmB) in the empirical treatment of IFIs within the Turkish healthcare system. A decision-analytic model was adopted, utilising data from a randomised, non-inferiority clinical trial and a panel of clinical experts in Turkey. A five-point composite outcome measure was used to evaluate both agents. Sensitivity analyses were performed. In the base-case scenario, CAS was preferred over L-AmB by Turkish Lira (TL) 3961 per patient treated, TL 12 904 per successfully treated patient and TL 3972 per death averted. One-way sensitivity analysis did not change the study outcome. Monte Carlo simulation concluded a 71.0% chance of the outcome favouring CAS. The results were most sensitive to changes in length of stay. This is the first economic evaluation of the empirical treatment of IFIs in Turkey and suggests that CAS is more cost effective than L-AmB., (Copyright © 2013 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

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.

Objective: The pricing of follow-on drugs, that offer only limited health benefits over existing therapeutic alternatives, is a recurring health policy debate. This study investigates whether follow-on therapeutic substitutes create price competition between branded hospital medicines., Methods: New follow-on drugs and their incumbent therapeutic competitors were identified from Danish sales and product registration data on hospital pharmaceuticals using medically relevant criteria. We examined whether follow-on drugs adopt lower prices than their incumbent competitors, and whether incumbent competitors react to entry of follow-ons through price adjustments using a random intercept panel model., Results: We found no evidence that follow-on drugs adopt lower prices than their incumbent competitors. Furthermore, potentially due to low sample size, we found no evidence that prices for incumbent pioneer products were significantly reduced as a reaction to competition from follow-on drugs., Conclusion: Competition between patented therapeutic substitutes did not seem to increase price competition and containment of pharmaceutical expenditures in the Danish hospital market. Strengthening hospitals' incentives to consider the price of alternative treatment options paired with a more active formulary management may increase price competition between therapeutic substitutes in the Danish hospital sector in the future., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Invasive fungal infections incur considerable costs to healthcare and are associated with high mortality. These infections are increasing, due in part to more intensive immunosuppressive regimens with longer periods of neutropenia for patients treated for conditions such as cancer and hematopoietic stem cell transplantation. Therapeutic strategies in treating invasive fungal infections include the initiation of empiric antifungal therapy. This early treatment is triggered by fever that is unresponsive to 48-72 h of broad-spectrum antibiotic therapy in high-risk patients, prior to diagnosis. Several antifungal agents are available for this purpose. Informed decisions with respect to the choice of antifungal drug require clinicians to consider both efficacy data of a particular drug and the economic consequences of using the drug. This enables a treatment decision to be based not only on drug acquisition cost, but also expenses associated with hospitalization, monitoring and managing adverse effects to the treatment(s) chosen.

Background: Febrile neutropenia (FN) is a serious complication following chemotherapy and is associated with significant mortality and financial expenditure. The aim of this study was to evaluate risk factors for longer length of stay (LOS) and mortality and cost of treatment among hospitalized adults with cancer who developed febrile neutropenia in Thailand., Materials and Methods: Information on illness of inpatients and casualties came from hospitals nationwide and from hospital withdrawals from the 3 health insurance schemes in fiscal 2010. The data covered 96% of the population and were analyzed by age groups, hospital level, and insurance year schemes in patients with febrile neutropenia., Results: A total of 5,809 patients were identified in the study. The mortality rate was 14%. The median LOS was 8.67 days and 69% of patients stayed for longer than 5 days. On bivariate analysis, age, cancer type, and infectious complications (bacteremia/sepsis, hypotension, fungal infections, and pneumonia) were significantly associated with longer LOS and death. On multivariate analysis, acute leukemia and infectious complications were linked with longer LOS and death significantly. The median cost of hospitalized FN was THB 33,686 (USD 1,122) with the highest cost observed in acute leukemia patients., Conclusions: FN in adult patients results in significant mortality in hospitalized Thai patients. Factors associated with increased mortality include older age (>70), acute leukemia, comorbidity, and infectious complications.

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., (© 2012 Blackwell Verlag GmbH.)

Background: Superficial fungal infections are common and treatment imposes economic burden on the patients. Government of India had introduced price control over griseofulvin and tolnaftate in 1995; however, this measure can only benefit the needy if the policy is harmonized with the health-care service provider, that is, dermatologists. The aim of this study was to evaluate the existing Government mechanisms over price control of antifungal medications and its reach to the people-in-need., Materials and Methods: A questionnaire-based, cross-sectional study was carried out over a period of 6 months. Questionnaire was mailed to members of a state branch of Indian Association of Dermatologists, Venereologists, and Leprologists. Responses reaching investigators within 2 months from the date of mailing were finally analyzed., Results: Among 93 (41.33%) respondents, only 6 (6.5%) were aware of existing price control over griseofulvin but none about tolnaftate. Thirty-nine (41.9%) respondents were in favor of introducing price control on terbinafine and 42 (45.2%) for itraconazole. The topically preferred antifungals were primarily azoles and terbinafine, while among systemic antifungals, dermatologists mostly preferred fluconazole and terbinafine. The choice of antifungals by the dermatologists matched with the evidence-based dermatology data., Conclusion: Currently, price-controlled antifungal drugs are less commonly used by practitioners. Although the dermatologists favor price control, the initiative undertaken by the Government has not reached them. This shows the need to bridge the gap between policy makers and health-care service providers to help the ailing population.

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.

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.

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.

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.

Background: The risks and benefits of infection prophylaxis are uncertain in children with cancer and thus, preferences should be considered in decision making. The purpose of this report was to describe the attitudes of parents, children and healthcare professionals to infection prophylaxis in pediatric oncology., Methods: THE STUDY WAS COMPLETED IN THREE PHASES: 1) An initial qualitative pilot to identify the main attributes influencing the decision to use infection prophylaxis, which were then incorporated into a discrete choice experiment; 2) A think aloud during the discrete choice experiment in which preferences for infection prophylaxis were elicited quantitatively; and 3) In-depth follow up interviews. Interviews were recorded verbatim and analyzed using an iterative, thematic analysis. Final themes were selected using a consensus approach., Results: A total of 35 parents, 22 children and 28 healthcare professionals participated. All three groups suggested that the most important factor influencing their decision making was the effect of prophylaxis on reducing the chance of death. Themes of importance to the three groups included antimicrobial resistance, side effects of medications, the financial impact of outpatient prophylaxis and the route and schedule of administration., Conclusion: Effect of prophylaxis on risk of death was a key factor in decision making. Other identified factors were antimicrobial resistance, side effects of medication, financial impact and administration details. Better understanding of factors driving decision making for infection prophylaxis will help facilitate future implementation of prophylactic regiments.

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.

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.

Invasive fungal infections are an important cause of mortality in oncology and haematology unit care. Immunosuppression allows the occurrence of Candida or Aspergillus infectious disease. Treatment is based on antifungal agents (liposomal amphotericin B, azoles and caspofungin) administrated alone. The lack of study does not yet validate the combination of two drugs which are not recommended in medical practice. The aim of this pharmacoeconomics study is to assess different therapeutic strategies compared to standard treatment. Health care system point of view is used. Results show that liposomal amphotericin B is the reference standard drug during no documented infection in term of cost. But, voriconazole does not have significative cost variation for Aspergillus disease. Same conclusion can be showed, in case of candidosis for caspofungin. The sensitivity analysis shows that daily cost treatment and body weight are variables with important impact on results. This preliminary analysis must be continued by a clinical study in order to assess different antifungal treatments., (Copyright © 2011 Elsevier Masson SAS. All rights reserved.)

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., (Copyright © 2011 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Background: Patients with a solid organ transplant (SOTs) and hematopoietic stem cell or bone marrow transplants (HSC/BMTs) are at risk of contracting invasive fungal infections (IFIs). Data on the economic burden of IFIs in the United States are sparse., Methods: We conducted a retrospective matched cohort study using the 2004-2005 Healthcare Cost and Utilization Project Nationwide Inpatient Sample. The IFI cohort included patients with ICD-9-CM codes indicating a transplant procedure and an IFI. Matched controls (transplant recipients without an IFI) were chosen based on age (10 year categories), sex, region, hospital type, year, and transplant type. Mortality, length of stay, and costs were reported overall, by transplant type, and by type of mycosis., Results: Nine thousand eight hundred ninety-six patients underwent SOT, and 4661 underwent HSC/BMT. Of these, 80 (0.8%) SOT and 111 (2.4%) HSC/BMT patients had an IFI. Mean age was 41.8 years (SOT) and 37.8 years (HSC/BMT). Aspergillosis was the most common infection. Patients with an IFI had a 5-fold increase in mortality, an additional 19.2 hospital days, and $55,400 in excess costs compared with patients without an IFI. Excess mortality, length of stay, and costs varied by type of transplant and mycosis., Conclusion: The clinical and economic burden of IFIs in transplant recipients may be high., (Copyright © 2011 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Mosby, Inc. All rights reserved.)

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.

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.

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., (© 2011 The Authors. Internal Medicine Journal © 2011 Royal Australasian College of Physicians.)

This review compares the pharmacology, spectrum of antifungal activity, pharmacokinetic and pharmacodynamic properties, safety and clinical efficacy of the three licensed echinocandins: caspofungin, micafungin and anidulafungin. Echinocandins inhibit the synthesis of 1,3-β-D-glucan, an essential component of the fungal cell wall, and represent a valuable treatment option for fungal infections. The echinocandins exhibit potent in vitro and in vivo fungicidal activity against Candida species, including azole-resistant pathogens. For all agents, strains with drug minimum inhibitory concentrations (MICs) of ≤ 2 μg/mL are considered susceptible; the MIC at which 90% of isolates tested were inhibited (MIC₉₀) values are typically <2 μg/mL but 100-fold higher MIC₉₀ values are seen with Candida parapsilosis (1-2 μg/mL) and Candida guilliermondii (1-4 μg/mL). Activity is comparable between the three agents, although limited data indicate that anidulafungin may have low MICs against C. parapsilosis and Candida glabrata strains that demonstrate elevated MICs to caspofungin and micafungin. All three drugs have good fungistatic activity against Aspergillus spp., although minimal effective concentrations of micafungin and anidulfungin are 2- to 10-fold lower than those for caspofungin. Synergistic/additive in vitro effects of echinocandins when combined with a polyene or azole have been observed. Clinical resistance to the echinocandins is rare despite case reports of caspofungin resistance in several Candida spp. Resistance has been attributed to mutations in the FKS1 gene within two hot spot regions, leading to amino acid substitutions, mostly at position 645 (serine), yet not all FKS1 mutants have caspofungin MICs of >2 μg/mL. Of the three echinocandins, the in vitro 'paradoxical effect' (increased growth at supra-MIC drug concentrations) is observed least often with anidulafungin. All echinocandins have low oral bioavailability, and distribute well into tissues, but poorly into the CNS and eye. Anidulafungin is unique in that it undergoes elimination by chemical degradation in bile rather than via hepatic metabolism, has a lower maximum concentration and smaller steady state under the concentration-time curve but longer half-life than caspofungin or micafungin. In children, dosing should be based on body surface area. Daily doses of caspofungin (but not micafungin and anidulafungin) should be decreased (from 50 to 35 mg) in moderate liver insufficiency. All echinocandins display concentration-dependent fungicidal (for Candida) or fungistatic (for Aspergillus) activity. The postantifungal effect is 0.9-20 hours against Candida and <0.5 hours against Aspergillus. The echinocandins are well tolerated with few serious drug-drug interactions since they are not appreciable substrates, inhibitors or inducers of the cytochrome P450 or P-glycoprotein systems. In parallel with the greater clinical experience with caspofungin, this agent has a slightly higher potential for adverse effects/drug-drug interactions, with the least potential observed for anidulafungin. Caspofungin (but not micafungin or anidulafungin) dosing should be increased if coadministered with rifampicin and there are modest interactions of caspofungin with calcineurin inhibitors. All three agents are approved for the treatment of oesophageal candidiasis, candidaemia and other select forms of invasive candidiasis. Only micafungin is licensed for antifungal prophylaxis in stem cell transplantation, whereas caspofungin is approved for empirical therapy of febrile neutropenia. Caspofungin has been evaluated in the salvage and primary therapy of invasive aspergillosis. Combination regimens incorporating an echinocandin showing promise in the treatment of aspergillosis. However, echinocandins remain expensive to use.

The incidence of invasive fungal infection has risen in recent years with the introduction of more intensive chemotherapy regimens and the advent of stem cell and solid-organ transplants. In patients undergoing chemotherapy, mortality rates ranging from 50 to 90% have been associated with documented invasive fungal infection. Voriconazole is a second-generation triazole, which is a synthesized derivative of fluconazole. It was first approved for marketing in the USA in 2002. Voriconazole has excellent bioavailability and is available in oral and intravenous dosage form. It has extended-spectrum antifungal activity whereby it is highly effective against a variety of fungal organisms, including Candida, Fusarium, Paecilomyces and Scedosporium species, but it is especially known for its activity against the Aspergillu s species. Voriconazole has become widely used for three types of treatment strategies (i.e., targeted, empirical and prophylactic). However, voriconazole is a high-cost antifungal agent and, therefore, its effectiveness should be scrutinized, taking into consideration its cost in relation to the costs of other comparable antifungal agents. This article summarizes the 18 identified peer-reviewed publications on the pharmacoeconomics of voriconazole in the English literature, up to March 2010, and provides a view on its future role in therapy. Comparisons with existing antifungals are provided when possible to illustrate the potential role of voriconazole in a clinical setting. The studies took place in a variety of countries and were all retrospective in nature, with the majority suggesting that voriconazole is a more cost-effective option for antifungal treatment. Of the 18 evaluations, 11 were related to the economic impact of voriconazole against invasive aspergillosis only. Economic data to guide the use of voriconazole as prophylaxis or empirical therapy as well as targeted therapy against invasive candidiasis remain limited.

The objective of this study is to determine a protocol for collecting acid-fast bacilli (AFB) and fungal intraoperative cultures during orthopedic procedures. An observational study was undertaken. Four hundred forty-six AFB cultures and 486 fungal cultures were processed over a 2-year period. The number of positive cultures was determined. A protocol specific to handling these types of specimens was developed. Cost analysis was completed to determine both the time and money saved if the new protocol was implemented. The infrequency of positive AFB and fungal cultures in this study suggests that it is only necessary to routinely request AFB and fungal cultures on 1 of 5 samples. Implementation of this protocol has potential to lead to substantial cost reduction and resource savings without diminishing patient outcomes., (Copyright © 2010. Published by Elsevier Inc.)

Posaconazole has been proven to be as effective as fluconazole in the prevention of invasive fungal infections (IFI) in allogeneic haematopoietic SCT patients with GVHD. We assessed, from the perspective of the Spanish National Health Service, the cost-effectiveness of posaconazole vs fluconazole in preventing IFI. A decision-analytic model was developed to assess the average per patient treatment costs, IFIs avoided, life-years gained (LYG) and incremental cost per LYG for each prophylactic treatment used (in euros at 2007 prices). Patients are assumed to have received either posaconazole or fluconazole. The probabilities of IFI, IFI-related death and death from other causes were obtained from a single clinical trial. Long-term mortality and costs were estimated from secondary sources. Posaconazole was associated with fewer IFIs (5.3 vs 9%), increased LYG (8.01 vs 7.78) and higher IFI-related costs ([euro]11 585 vs [euro]6 959) per patient compared with fluconazole. The incremental cost-effectiveness of posaconazole vs fluconazole was estimated at [euro]20 246 per LYG. There was a 70% probability that posaconazole is cost-effective at a [euro]30 000 per LYG threshold. In conclusion, compared with fluconazole, posaconazole prophylaxis is a cost-effective strategy for the prevention of IFI in 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.