Budget Impact of Microbial Cell-Free DNA Testing Using the Karius® Test as an Alternative to Invasive Procedures in Immunocompromised Patients with Suspected Invasive Fungal Infections.

BACKGROUND: Invasive fungal infection is a major source of morbidity and mortality. The usage of microbial cell-free DNA for the detection and identification of invasive fungal infection has been considered as a potential alternative to invasive procedures allowing for rapid results. OBJECTIVE: This analysis aimed to assess the budget implications of using the Karius® Test in patients suspected of invasive fungal infection in an average state in the USA from a healthcare payer perspective. METHODS: The analysis used a decision tree to capture key stages of the patient pathway, from suspected invasive fungal infection to either receiving treatment for invasive fungal infection or being confirmed as having no invasive fungal infection. The analysis used published costs and resource use from a targeted review of the literature. Because of the paucity of published evidence on the reduction of diagnostic tests displaced by the Karius Test, the analysis used a 50% reduction in the use of bronchoscopy and/or bronchoalveolar lavage. The impact of this reduction was tested in a scenario analysis. RESULTS: The results of the analysis show that the introduction of the Karius Test is associated with a cost saving of US$2277 per patient; when multiplied by the estimated number of cases per year, the cost saving is US$17,039,666. The scenario analysis showed that the Karius Test only had an incremental cost of US$87 per patient when there was no reduction in bronchoscopy and bronchoalveolar lavage. CONCLUSIONS: The Karius Test may offer a valuable and timely option for the diagnosis of invasive fungal infection through its non-invasive approach and subsequent cost savings.

Cost-effectiveness of antifungal prophylaxis, preemptive therapy, or empiric treatment following allogeneic hematopoietic stem cell transplant.

BACKGROUND: Invasive fungal infection (IFI) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation (HSCT) that is also associated with excess healthcare costs. Current approaches include universal antifungal prophylaxis, preemptive therapy based on biomarker surveillance, and empiric treatment initiated in response to clinical signs/symptoms. However, no study has directly compared the cost-effectiveness of these treatment strategies for an allogeneic HSCT patient population. METHODS: We developed a state transition model to study the impact of treatment strategies on outcomes associated with IFIs in the first 100 days following myeloablative allogeneic HSCT. We compared three treatment strategies: empiric voriconazole, preemptive voriconazole (200 mg), or prophylactic posaconazole (300 mg) for the management of IFIs. Preemptive treatment was guided by scheduled laboratory surveillance with galactomannan (GM) testing. Endpoints were cost and survival at 100 days post-HSCT. RESULTS: Empiric treatment was the least costly ($147 482) and was equally effective (85.2% survival at 100 days) as the preemptive treatment strategies. Preemptive treatments were slightly more costly than empiric treatment (GM cutoff ≥ 1.0 $147 910 and GM cutoff ≥ 0.5 $148 108). Preemptive therapy with GM cutoff ≥ 1.0 reduced anti-mold therapy by 5% when compared to empiric therapy. Posaconazole prophylaxis was the most effective (86.6% survival at 100 days) and costly ($152 240) treatment strategy with a cost of $352 415 per life saved when compared to empiric therapy. CONCLUSIONS: One preemptive treatment strategy reduced overall anti-mold drug exposure but did not reduce overall costs. Prevention of IFI using posaconazole prophylaxis was the most effective treatment strategy and may be cost-effective, depending upon the willingness to pay per life saved.

Treatment of immunocompromised patients with suspected invasive fungal infections: economic analysis of diagnostic-driven versus empirical strategies in Algeria and Egypt.

Background: Invasive fungal infections (IFIs) in immunocompromised patients are associated with high mortality and treatment costs. Identifying appropriate, cost-effective treatment strategies is crucial to reduce the burden of IFIs. This economic assessment compared strategies for treating immunocompromised patients in Algeria and Egypt.Methods: We developed a decision analytic model incorporating clinical and cost inputs associated with a diagnostic-driven (DD) and standard empirical (SE) strategy. Costs and clinical outcomes were used to calculate incremental cost-effectiveness ratios (ICERs) per death avoided.Results: In both countries, 73.8 (DD) and 125.3 (SE) hypothetical patients per 1,000 received antifungal therapy; 73.8 (DD) and 32.7 (SE) had diagnosed IFIs. Survival at 180 days was similar between DD and SE strategies in Algeria (92.0% vs 91.6%) and Egypt (90.2% vs 90.0%). Total costs per patient were lower with the DD than SE strategy (Algeria: $839 vs $1,591; Egypt: $4,077 vs $4,717). ICERs indicated that the DD compared with SE strategy was associated with better clinical outcomes at a lower overall cost in both countries.Conclusion: Diagnostic-driven compared to empirical therapy may be cost-saving in Algeria and Egypt for the management of immunocompromised patients with persistent neutropenic fever, with no increase in mortality.

Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden.

BACKGROUND: Voriconazole is well established as standard treatment for invasive aspergillosis (IA). In 2017, isavuconazole, a new antifungal from the azole class, with a broader pathogen spectrum, was introduced in Sweden. A model has therefore been developed to compare the cost-effectiveness of isavuconazole and voriconazole in the treatment of possible IA in adults in Sweden. METHODS: The cost-effectiveness of isavuconazole versus voriconazole was evaluated using a decision-tree model. Patients with possible IA entered the model, with 6% assumed to actually have mucormycosis. It was also assumed that pathogen information would become available during the course of treatment for only 50% of patients, with differential diagnosis unavailable for the remainder. Patients who were considered unresponsive to first-line treatment were switched to second-line treatment with liposomal amphotericin-B. Data and clinical definitions included in the model were taken from the published randomised clinical trial comparing isavuconazole with voriconazole for the treatment of IA and other filamentous fungi (SECURE) and the single-arm, open-label trial and case-control analysis of isavuconazole for the treatment of mucormycosis (VITAL). A probabilistic sensitivity analysis was used to estimate the combined parameter uncertainty, and a deterministic sensitivity analysis and a scenario analysis were performed to test the robustness of the model assumptions. The model followed a Swedish healthcare payer perspective, therefore only considering direct medical costs. RESULTS: The base case analysis showed that isavuconazole resulted in an incremental cost-effectiveness ratio (ICER) of 174,890 Swedish krona (SEK) per additional quality adjusted life-year (QALY) gained. This was mainly due to the efficacy of isavuconazole against IA and mucormycosis, as opposed to voriconazole, which is only effective against IA. Sensitivity and scenario analyses of the data showed that the average ICER consistently fell below the willingness to pay (WTP) threshold of 1,000,000 SEK. The probability of isavuconazole being cost-effective at a WTP of 170,000 SEK per QALY gained was 50% and at a WTP of 500,000 SEK per QALY gained was 100%. CONCLUSIONS: This model suggests that the treatment of possible IA with isavuconazole is cost-effective compared with treatment with voriconazole from a Swedish healthcare payer perspective.

The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan.

Patients with invasive fungal diseases (IFDs) generally have a high mortality rate, and resistance to antifungal drugs and the high costs associated with it have led to recent problems, necessitating the appropriate use of antifungals. To this end, we launched Antifungal Stewardship Programs (AFSPs) in our hospital. Patients who were systemically administered antifungals from January 2011 to December 2016 were enrolled this study and divided into pre-intervention and intervention groups. No significant difference was observed in defined daily doses per 1000 patient-days (23.3 ± 8.0 vs 20.4 ± 10.8, p = 0.251) between the groups. The monthly average for the days of therapy per 1000 patient-days was significantly lower in the intervention group (15.1 ± 3.1 vs 12.7 ± 4.3, p = 0.009). The cost of the antifungals reduced over the 3-year period by $260,520 (13.5%). Furthermore, a decreasing trend was observed in both the 30-day mortality (40.9% vs 30.0%, p = 0.414) and in-hospital mortality (63.6% vs 36.7%, p = 0.054) in patients with candidemia. Our results indicate that AFSPs are efficacious and cost-effective approaches.

Cost analysis of bronchoalveolar lavage and respiratory tract biopsies in the diagnosis and management of suspected invasive fungal infection in children with cancer or who have undergone stem cell transplant.

BACKGROUND: Identification of an organism is the gold standard for the diagnosis of fungal infection; however, we have previously shown that invasive procedures infrequently lead to a change in management in children with cancer or who have undergone stem cell transplant with suspected respiratory tract invasive fungal infection (RT-IFI). There is also a paucity of data on the cost of RT-IFI in this population. We therefore compared the costs of RT-IFI diagnosed based on CT scan alone versus those who underwent a bronchoalveolar lavage (BAL) or respiratory tract biopsy (RTB). PROCEDURE: We collected cost data on patients at a single center undergoing chemotherapy or who were post-hematopoietic stem cell transplant (HSCT) and were suspected of having RT-IFI between 2007 and 2012. Cost data were included for 14 days from the day of their diagnostic CT scan or procedure. RESULTS: Cost data were available for 76 patients. Thirty-six patients were diagnosed with suspected RT-IFI based on CT only, and 40 patients underwent BAL or RTB. Costs related to chest X-rays (CXRs), inpatient/intensive care unit (ICU) beds, anesthesia, operating room (OR) time, and procedures were significantly higher in the BAL/RTB group versus CT scan group (all P < 0.01). Costs related to CT scans were significantly higher in the CT scan group (P = 0.0002). Overall costs were significantly higher for patients who underwent BAL or RTB versus CT scan only (P < 0.0001). CONCLUSION: Our previous data showed that BAL and RTB infrequently led to a change in management in this population. We now demonstrate that this strategy is costly as well.

Impact of supplemental parenteral nutrition early during critical illness on invasive fungal infections: a secondary analysis of the EPaNIC randomized controlled trial.

OBJECTIVE: In the EPaNIC RCT (N=4640), postponing the administration of parenteral nutrition (PN) to beyond 1 week in the intensive care unit (ICU) (late-PN) reduced the number of ICU-acquired infections and the costs for antimicrobial drugs compared with initiation of PN within 24-48 hours of admission (early-PN). In a secondary analysis, we hypothesize that late-PN reduces the odds to acquire an invasive fungal infection (IFI) in the ICU. METHODS: The impact of late-PN (N=2328) versus early-PN (N=2312) on acquired IFI and on the likelihood to acquire an IFI over time was assessed in univariable and multivariable analyses. Subsequently, we performed multivariable analyses to assess the effect of the mean total daily administered calories from admission until day 3, day 5, and day 7 on the likelihood over time of acquiring an IFI. RESULTS: Fewer late-PN patients acquired an IFI compared with early-PN patients (77/2328 versus 112/2312) (p 0.008). After adjusting for risk factors, the odds to acquire an IFI and the likelihood of acquiring an IFI at any time were lower in late-PN (adjusted odds ratio 0.66, 95% CI 0.48-0.90, p 0.009; adjusted hazard ratio (HRadj) 0.70, 95% CI 0.52-0.93, p 0.02). Larger caloric amounts from admission until day 7 were associated with a higher likelihood to acquire an IFI over time (HRadj 1.09, 95% CI 1.02-1.16, p 0.009). CONCLUSION: Postponing PN to beyond 1 week and smaller caloric amounts until day 7 in the ICU reduced ICU-acquired IFIs and the likelihood to develop an IFI over time.

Healthcare burden of probable and proven invasive mucormycosis: a multi-centre cost-of-illness analysis of patients treated in tertiary care hospitals between 2003 and 2016.

BACKGROUND: Invasive mucormycosis (IM) is a rare invasive fungal infection with a high mortality rate. However, data concerning the clinical and economic burden of IM are scarce. AIM: To evaluate the direct treatment costs and additional expenditures of patients with IM. METHODS: A retrospective cost-of-illness analysis of cases with IM extracted from FungiScope - Global Registry for Emerging Fungal Infections, accessible through the epidemiological research platform www.ClinicalSurveys.net, was undertaken. Results of patients with IM were compared with those of matched patients with similar underlying conditions based on the German Diagnosis Related Group (G-DRG) coding. FINDINGS: Out of 46 patients with probable/proven IM, 31 (67%) patients were male and the median age was 53 years (range 11-88 years). Forty-two patients (92%) had haematological diseases as the most common risk factor. Analysis of cost factors identified antifungal treatment due to IM as the primary cost driver [€22,816, 95% confidence interval (CI) €15,036-32,346], with mean overall direct treatment costs of €53,261 (95% CI €39,660-68,825). Compared with matched patients, patients with IM were treated in hospital for 26.5 additional days (standard deviation 31.8 days; P < 0.001), resulting in mean additional costs of €32,991 (95% CI €21,558-46,613; P < 0.001). Probable IM, as well as absence of chemotherapy, surgical measures due to IM, and antifungal prophylaxis were associated with lower overall costs. Nineteen patients (41.3%) died during hospitalization. CONCLUSION: This study demonstrates the considerable healthcare burden of IM. The choice of antifungal agent for treatment of IM had no impact on overall cost.

[Evaluation of the prescription, consumption and costs of antifungal drugs in a pediatric hospital in Chile]. / Evaluación de la indicación, consumo y costos de antifúngicos en un hospital pediátrico de Chile.

BACKGROUND: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. AIM: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. METHODS: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. RESULTS: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. CONCLUSIONS: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.

Monetary costs and hospital burden associated with the management of invasive fungal infections in Mexico: a multicenter study.

BACKGROUND: Invasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim To report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. METHODS: This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. RESULTS: Two-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p<0.0001). The overall incidence of IFIs was 4.8 cases (95% CI=0.72-8.92) per 1000 discharges and 0.7 cases (95% CI=0.03-1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI=-1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI=-3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI=-0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). CONCLUSIONS: IFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

Monetary costs and hospital burden associated with the management of invasive fungal infections in Mexico: a multicenter study

ABSTRACT Background: Invasive fungal infections (IFIs) affect >1.5 million people per year. Nevertheless, IFIs are usually neglected and underdiagnosed. IFIs should be considered as a public-health problem and major actions should be taken to tackle them and their associated costs. Aim To report the incidence of IFIs in four Mexican hospitals, to describe the economic cost associated with IFIs therapy and the impact of adverse events such as acute kidney injury (AKI), liver damage (LD), and ICU stay. Methods: This was a retrospective, transversal study carried-out in four Mexican hospitals. All IFIs occurring during 2016 were included. Incidence rates and estimation of antifungal therapy's expenditure for one year were calculated. Adjustments for costs of AKI were done. An analysis of factors associated with death, AKI, and LD was performed. Results: Two-hundred thirty-eight cases were included. Among all cases, AKI was diagnosed in 16%, LD in 25%, 35% required ICU stay, with a 23% overall mortality rate. AKI and LD showed higher mortality rates (39% vs 9% and 44% vs 18%, respectively, p < 0.0001). The overall incidence of IFIs was 4.8 cases (95% CI = 0.72-8.92) per 1000 discharges and 0.7 cases (95% CI = 0.03-1.16) per 1000 patients-days. Invasive candidiasis showed the highest incidence rate (1.93 per 1000 discharges, 95% CI = −1.01 to 2.84), followed by endemic IFIs (1.53 per 1000 discharges 95% CI = −3.36 to 6.4) and IA (1.25 per 1000 discharges, 95% CI = −0.90 to 3.45). AKI increased the cost of antifungal therapy 4.3-fold. The total expenditure in antifungal therapy for all IFIs, adjusting for AKI, was $233,435,536 USD (95% CI $6,224,993 to $773,810,330). Conclusions: IFIs are as frequent as HIV asymptomatic infection and tuberculosis. Costs estimations allow to assess cost-avoidance strategies to increase targeted driven therapy and decrease adverse events and their costs.

Evaluación de la indicación, consumo y costos de antifúngicos en un hospital pediátrico de Chile / Evaluation of the prescription, consumption and costs of antifungal drugs in a pediatric hospital in Chile

Resumen Introducción: El incremento de la enfermedad fúngica invasora (EFI) en pacientes inmunocomprometidos ha conducido a la frecuente prescripción de fármacos altamente activos pero de elevado costo económico. Objetivo: Caracterizar el uso de antifúngicos, evaluar su indicación y determinar consumo y costos asociados. Métodos: Estudio descriptivo, retrospectivo, desde enero de 2015 a abril de 2016. Auditoría de prescripciones y revisión de fichas clínicas; cada prescripción se clasificó de acuerdo a si correspondía a una EFI posible, probable o probada. Se calcularon consumos y costos de tratamientos. Resultados: Se auditaron 152 prescripciones de antifúngicos en 79 pacientes. El costo total de los medicamentos antifúngicos fue de US$ 714.413. El 52,1% del gasto (US $ 372.319) correspondió a indicaciones en EFI probada, 10,7% (US $ 76.377) EFI probable, 0.8% (US $ 5.638) no-EFI, 12,2% (US $ 87.459) EFI posibles y 1,5% (US $ 10.896) EFI descartada y 22,6% (US$ 161.723) fue profilaxis. El mayor consumo fue en indicaciones relacionadas a EFI probada con un DOT probada de 10,54 días, siendo anfotericina B liposomal y voriconazol iv los fármacos con mayor consumo con un DOTprobada AnBL de 3,15 y DOT probada voriconazol iv de 3,01. Conclusiones: El consumo de medicamentos antifúngicos genera altos costos correspondiente al 12% del presupuesto total de farmacia de nuestra institución. El gasto se asoció principalmente a indicaciones en EFI probadas, voriconazol y anfotericina B liposomal los con mayor consumo, lo que sumado a su alto costo y días prolongados de terapia generan un gran impacto en el presupuesto.

Background: The increase of invasive fungal disease (IFD) in immunocompromised patients has led to the frequent prescription of highly active antifungal drugs but with a high economic cost. Aim: To characterize the use of antifungals drugs, evaluate its prescription and determine consumption and associated costs. Methods: Retrospective descriptive study from January 2015 to April 2016. Audit of prescriptions and review of clinical files. Each prescription was classified according to whether it corresponded to a possible, probable or proven invasive fungal disease (IFD). Consumptions and treatment costs were calculated. Results: 152 antifungal prescriptions were audited in 79 patients. The total cost of antifungal medications was US $ 714,413. 52.1% of the expenditure (US $ 372,319) corresponded to indications in proven IFD, 10.7% (US $ 76,377) probable IFD, 0.8% (US $ 5,638) non-IFI, 12.2% (US $ 87,459) IFD possible and 1.5% (US $ 10,896) non-IFD and 22.6% (US $ 161,723) was prophylaxis. The highest consumption was in indications related to IFD tested with a proven DOT of 10.54 days, with liposomal amphotericin B and iv voriconazole the drugs with the highest consumption with a DOT probable_AnBL of 3.15 and DOT proven voriconazole iv of 3.01. Conclusions: The consumption of antifungal drug medications generates high costs at 12% of the total pharmacy budget of our institution. The expense was associated mainly with the indications in IFI tested the voriconazole and amphotericin B liposomal with the highest consumption which added to its high cost and prolonged days of general therapy a big impact in the budget.

Epidemiology and Outcomes of Hospitalizations With Invasive Aspergillosis in the United States, 2009-2013.

Background: Though invasive aspergillosis (IA) complicates care of up to 13% of patients with immunocompromise, little is known about its morbidity and mortality burden in the United States. Methods: We analyzed the Health Care Utilization Project's data from the Agency for Healthcare Research and Quality for 2009-2013. Among subjects with high-risk conditions for IA, IA was identified via International Classification of Diseases, Ninth Revision, Clinical Modification codes 117.3, 117.9, and 484.6. We compared characteristics and outcomes between those with (IA) and without IA (non-IA). Using propensity score matching, we calculated the IA-associated excess mortality and 30-day readmission rates, length of stay, and costs. Results: Of the 66634683 discharged patients meeting study inclusion criteria, 154888 (0.2%) had a diagnosis of IA. The most common high-risk conditions were major surgery (50.1%) in the non-IA and critical illness (41.0%) in the IA group. After propensity score matching, both mortality (odds ratio, 1.43; 95% confidence interval, 1.36-1.51) and 30-day readmission (1.39; 1.34-1.45) rates were higher in the IA group. IA was associated with 6.0 (95% confidence interval, 5.7-6.4) excess days in the hospital and $15542 ($13869-$17215) in excess costs per hospitalization. Conclusions: Although rare even among high-risk groups, IA is associated with increased hospital mortality and 30-day readmission rates, excess duration of hospitalization, and costs. Given nearly 40000 annual admissions for IA in the United States, the aggregate IA-attributable excess costs may reach $600 million annually.

Antifungal treatment in haematological and oncological patients: Need for quality assessment in routine care.

Invasive fungal infections in haematological and oncological patients have a major impact on morbidity, mortality and treatment costs. Therefore, rational use of antifungal agents is important for optimal patient care and resource use. The study's objective was to analyse antifungal usage in a German tertiary teaching hospital, department of haematology and oncology, to evaluate quality of antifungal treatment and to assess the need for an antifungal stewardship programme. This retrospective observational study included patients ≥18 years receiving systemic antifungals for prophylaxis or therapy of invasive fungal infection between January and June 2016. Appropriateness of antifungal prescriptions was evaluated in accordance with guidelines of the German Society of Haematology and Oncology (DGHO) and drug labelling. In total, 104/1278 (8.1%) patients received antifungals. One hundred seventy-one antifungals were prescribed: 48 for prophylaxis, 104 for empirical and 19 for targeted therapy. In 127 (74.3%) prescriptions, indication was appropriate, and in 132 (77.2%), choice of drug. Antifungals were correctly dosed in 131 prescriptions (76.6%). Thirty-four antifungals (20.0%) were co-administrated with interacting drugs (5 mild to moderate, 29 severe interactions). Results of this analysis demonstrate that use of systemic antifungals in routine care differs in a substantial number of patients from guideline and labelling recommendations. To optimise antifungal use, the implementation of antifungal stewardship programmes seems to be justified.

Economic evaluation of azoles as primary prophylaxis for the prevention of invasive fungal infections in Spanish patients undergoing allogeneic haematopoietic stem cell transplant.

Patients undergoing allogeneic haematopoietic stem cell transplantation (alloHSCT) are at risk of developing invasive fungal infections (IFIs). Even with introduction of oral triazole antifungal agents (fluconazole, itraconazole, posaconazole and voriconazole) IFI-associated morbidity and mortality rates and economic burden remain high. Despite their proven efficacy, it is currently unknown which is the most cost-effective antifungal prophylaxis (AFP) agent. To determine the costs and outcomes associated with AFP, a decision-analytic model was used to simulate treatment in a hypothetical cohort of 1000 patients undergoing alloHSCT from the perspective of the Spanish National Health System. Generic itraconazole was the least costly AFP (€162) relative to fluconazole (€500), posaconazole oral suspension (€8628) or voriconazole (€6850). Compared with posaconazole, voriconazole was associated with the lowest number of breakthrough IFIs (36 vs 60); thus, the model predicted fewer deaths from breakthrough IFI for voriconazole (24) than posaconazole (33), and the lowest predicted costs associated with other licensed antifungal treatment and IFI treatment in a cohort of 1000. Voriconazole resulted in cost savings of €4707 per patient compared with posaconazole. Itraconazole demonstrated a high probability of being cost-effective. As primary AFP in alloHSCT patients 180 days posttransplant, voriconazole was more likely to be cost-effective than posaconazole regarding cost per additional IFI and additional death avoided.