Clinical and health economic impact of isavuconazole for treatment of invasive aspergillosis and mucormycosis: a retrospective, matched multicentre cohort study in Germany.

Introduction

The treatment of invasive fungal diseases (IFDs), such as invasive aspergillosis (IA) and mucormycosis (IM), is challenging due to emerging resistance and the need for early therapeutic intervention [ 1 – 3 ]. IFDs are life-threatening infections that particularly affect immunocompromised individuals, with mortality rates reaching up to 75% [ 4 – 8 ]. A major reason for fatal outcomes is the considerable low rate of response to first-line treatment (e.g., due to nephrotoxicity), which often necessitates salvage therapy with a poor prognosis [ 9 , 10 ]. The incidence of IM, which is also known for high morbidity and mortality, has increased over the past years [ 8 , 11 ]. In addition to the clinical burden of IFDs, recent studies have demonstrated high treatment costs [ 12 , 13 ]. Additionally, the rising prevalence of immunocompromised patients and the overall increase in IFDs underscore the urgent need to develop new treatment strategies [ 8 ].

Isavuconazole, a triazole antifungal agent, has a broad spectrum of activity against many pathogenic fungi and a favourable side-effect profile [ 2 , 14 – 16 ]. It was approved in 2015 by the U.S. Food and Drug Administration (FDA) for treating IA and IM and by the European Medicines Agency (EMA) for IA and IM in patients for whom L-AmB is not appropriate [ 16 – 19 ]. The pivotal phase III SECURE trial demonstrated that isavuconazole is non-inferior to voriconazole for the primary treatment of IA and has a better safety profile. For IM, the single-arm phase III VITAL trial showed favourable efficacy for isavuconazole compared to a matched cohort of patients treated with L-AmB [ 17 , 18 ].

Despite this, real-world data on the clinical and health economic outcomes of isavuconazole in treatment of IA and IM, particularly outside of clinical trials, remain scarce [ 8 , 17 ]. To date, only a few studies have modelled its cost-effectiveness based on the SECURE and VITAL trials [ 13 , 20 – 22 ]. We therefore performed a multicentre, retrospective matched cohort study to evaluate the clinical effectiveness and health economic burden of isavuconazole as a first-line treatment for IA and IM of patients with haematological malignancies in a real-world setting in Germany.

Methods

Study design and study population

This retrospective, multicentre cohort study was conducted at six German tertiary care centres with extensive experience in the treatment of haematological and oncological diseases. We applied modified intention-to-treat approach using a matched-pair design with a 1:1 ratio, comparing patients who received first-line treatment with isavuconazole (case group) to those treated with L-AmB or voriconazole (control group) between January 2016 and May 2021.

We included patients at the age of 18 years or older with a haematological or oncological disease and the evidence of proven, probable, or possible IA or IM, as defined by the 2008EORTC/MSG revised criteria [ 23 ]. Matching was performed based on the concordance of the following criteria in descending order of priority: (i) type and grade of fungal infection; (ii) APACHE (Acute Physiology and Chronic Health Evaluation) II score, if treated on intensive care unit (ICU); (iii) underlying condition favouring fungal infection (haematopoietic cell transplantation [HCT], aplasia following chemotherapy, other forms of immunosuppression, other reason); (iv) age; and (v) sex. The study was conducted in line with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement, the Consolidated Health Economic Evaluation Reporting Standards 2022 (CHEERS), as well as national and international recommendations for health economic evaluation [ 24 – 27 ].

Study objectives

The primary objective was to compare the clinical effectiveness and overall direct treatment costs of patients with IA or IM receiving first-line treatment with isavuconazole vs. L-AmB or voriconazole in a real-world setting. Clinical outcomes included risk factors for IFD, grade of IA and IM, clinical symptoms, diagnostic tests, and length of hospitalisation. The health economic analysis assessed the direct costs incurred during the hospital stay.

Data collection and management

Data collection was performed retrospectively after regular hospital discharge or death by using data from standard-of-care medical records. Data were documented into a web-based electronic case report form (eCRF) in anonymised form accessible via www.clinicalsurveys.net , by internal medicine specialists at each participating centre. Data monitoring and query management were centrally performed by the lead study site, University Hospital Cologne.

Healthcare resource utilization and cost analysis

The healthcare resource utilization and cost analysis was conducted from the perspective of the German healthcare system [ 26 ]. Costs for treatment on hospital ward were calculated based on the German Diagnosis Related Groups (G-DRG) systematic provided by Institute for the Hospital Renumeration System (InEK, Institut für das Entgeltsystem im Krankenhaus) and represented personnel and material costs for the years 2016 to 2021 [ 28 ]. Drug acquisition costs for IFD treatment were calculated by using the pharmacy retail price from 2024 extracted from the Rote Liste ® , a comprehensive German drug directory [ 29 ]. To ensure comparability of hospitalisation and antifungal drug acquisition costs, the micro-costing approach used year 2024 values expressed in Euros (€). Indirect costs, such as productivity losses due to illness related disability or death before retirement age, were excluded from the analysis due to the severity of haematological and oncological diseases.

Statistical analysis

RStudio version 4.5.0 (from 2025-04-11) was used for data analysis. Descriptive statistics were reported as mean with 95% confidence interval (95% CI) and median with interquartile range (IQR) and range. Sociodemographic and clinical differences between the case and control groups were assessed using the Pearson’s chi-squared test, Mann-Whitney-U test, log rank test or Student’s t-test (two-sided), as appropriate, applying a significance level of p < 0.05. Non-normally distributed cost values were analysed and compared by using Welch’s bootstrapped t-test with 10,000 replications and a starting point for the Mersenne twister at 1,000. A multivariate generalised linear model (GLM) with gamma distribution and log-link function was used to identify predictors of overall direct treatment costs. Results from the GLM were reported as odds ratios (OR) with 95% CIs. Only predictors with a significance level of p ≤ 0.1 in univariate regression analyses were evaluated in the GLM.

Results

Study population

A total of 198 patients with IA or IM were included in this retrospective matched cohort study. Ninety-nine cases treated with isavuconazole were matched with 99 controls that received L-AmB or voriconazole as first-line treatment. For seven patients in the case group, no suitable patients in the control group could be identified at the same study site and therefore they were matched with patients in the control group from other study sites. Patient characteristics are presented in Table 1 , with the classification of IFD being the only variable showing significant differences between the two groups ( p = 0.039).

Table 1 Patient characteristics of the total study population Isavuconazole group ( n = 99) Control group ( n = 99) p value Age in years; Median (Range) 57 (19–86) 59 (28–77) 0.306 a Female sex; n (%) 34 (34) 32 (32) 0.763 b Ethnic origin; n (%) 1.000 c Caucasian 91 (92) 92 (93) Asian 2 (2) 2 (2) Sub-saharan African/Afro-American 1 (1) 0 (0) Body Mass Index; Mean (95% CI) 24.1 (23.2–25.1) 24.3 (23.4–25.2) 0.732 d Risk factor**; n (%) Neutropenia 46 (46) 37 (37) 0.195 b Immunosuppressive therapy 38 (38) 45 (45) 0.313 b Allogeneic HCT 32 (32) 23 (23) 0.153 b Acute kidney injury 23 (23) 19 (19) 0.487 b Intensive Care Treatment 15 (15) 13 (13) 0.683 b Diabetes mellitus 13 (13) 13 (13) 1.000 b Lymphocytopenia 12 (12) 14 (14) 0.674 b Chronic pulmonary disease 8 (8) 11 (11) 0.469 b Invasive ventilation 10 (10) 7 (7) 0.447 b Acute GvHD grade 1–2 13 (13) 4 (4) 0.224 b Acute GvHD grade 3–4 6 (6) 5 (5) 0.756 b Chronic graft versus host disease 7 (7) 4 (4) 0.352 b Autologous HCT 2 (2) 6 (6) 0.149 b Underlying haematological/ oncological disease; n (%) 0.711 b Haematological 95 (96) 95 (96) Oncological 3 (3) 4 (4) Haematological disease; n (%) 95 (96) 95 (96) 0.267 b Acute myeloid leukaemia 44 (46) 49 (52) Non-Hodgkin-Lymphoma 13 (14) 12 (13) Acute lymphoblastic leukaemia 8 (8) 5 (5) Chronic lymphoblastic leukaemia 7 (7) 8 (8) Multiple Myeloma 2 (2) 7 (7) Other 21 (22) 13 (14) Invasive fungal disease; n (%) Invasive aspergillosis 88 (89) 92 (93) 0.323 b Invasive mucormycosis 13 (13) 7 (7) 0.157 b Classification of invasive mycosis; n (%) 0.039 b * Possible 34 (34) 33 (33) Probable 44 (44) 57 (58) Proven 21 (21) 9 (9) Host factors***; n (%) Neutropenia (neutrophil cells < 500 µl) 60 (61) 62 (63) 0.840 b Immunosuppressive therapy 51 (52) 54 (55) 0.725 b Persistent fever (> 96 h) 28 (28) 36 (36) 0.243 b Therapy with corticosteroids ( > = 2 weeks) 24 (24) 15 (15) 0.100 b Signs and symptoms of GvHD after allogeneic HCT 18 (18) 13 (13) 0.313 b Mycological criteria; n (%) Conventional mycological examinations 76 (77) 75 (76) 0.766 b Non-culture-based antigen tests and molecular methods 70 (71) 78 (79) 0.232 b Tissue samples and liquid materials 85 (86) 91 (92) 0.238 b Abbreviations: CI, Confidence Interval; GvHD, graft-versus-host-disease; HCT, hematopoietic cell transplantation a Mann-Whitney U-test b Pearson chi-square test (two-tailed) c Fisher´s exact test d Student t-test * p -value < 0.05 ** Risk factors denote conditions or exposures present prior to the diagnosis of invasive aspergillosis or mucormycosis *** Host factors are defined as conditions present at the time of diagnosis of invasive aspergillosis or mucormycosis

Across both groups, the most common risk factors for IA or IM were neutropenia, immunosuppressive therapy, allogeneic HCT and acute kidney injury. 96% of the patients in both groups had an underlying haematological disease, with acute myeloid leukaemia and non-Hodgkin lymphoma being the most prevalent diagnoses. Most of the patients in both groups had IA, while IM was diagnosed in 13% ( n = 13) of patients in the case group compared to 7% ( n = 7) in the control group with proven and probable cases only ( p = 0.157). Two patients (2%) in the isavuconazole group had a concurrent diagnosis of both, IA and IM. The most commonly reported symptoms of IM and IA patients in the isavuconazole and control group were fever (64% vs. 68%), cough (30% vs. 30%), dyspnoea (29% vs. 30%), and pain (15% vs. 16%).

Treatment and hospitalisation

The median length of hospital stay (LOS) was 44 days (IQR 27–74 days) in the isavuconazole group and 39 days (IQR 26–56 days) in the control group ( p = 0.091, Table 2 ). Median treatment durations in the intermediate care unit and ICU did not differ between both groups, while patients in the control group required significantly longer durations of mechanical ventilation compared to the isavuconazole group.

Table 2 Hospitalisation and treatment details Isavuconazole group ( n = 99) Control group ( n = 99) p value Hospitalisation I ; n (%) 97 (98) 98 (99) 1.000 d Total days; Median (IQR) 44 (27–74) 39 (26–56) 0.091 a Normal ward; n (%) 89 (90) 84 (85) 0.285 Total days; Median (IQR) 38 (22–67) 33 (19–50) 0.161 a Intermediate care unit; n (%) 34 (34) 38 (38) 0.555 Total days; Median (IQR) 6 (3–12) 8 (2–27) 0.529 a Intensive care unit; n (%) 41 (41) 43 (43) 0.774 Total days; Median (IQR) 15 (6–22) 15 (6–29) 0.778 a Mechanical ventilation; n (%) 24 (24) 30 (30) 0.338 Total hours; Median (IQR) 233 (41–448) 358 (226–697) 0.044 a * Antifungal treatment Isavuconazole I ; n (%) 92 (93) - - Duration (days); Median (IQR) 12 (5–23) - - Liposomal Amphotericin B; n (%) 47 (47) 60 (61) 0.064 b Duration (days); Median (IQR) 20 (10–33) 13 (8–28) 0.551 a Voriconazole; n (%) 31 (31) 67 (68) < 0.001 b *** Duration (days); Median (IQR) 9 (6–27) 12 (4–29) 0.111 a Abbreviations: IQR, interquartile range I n -values differ due to missing data a Mann-Whitney U-test b Pearson chi-square test (two-tailed) c Student t-test d Fisher´s exact test * p -value < 0.05; *** p -value < 0.001

Patients in the case group were treated with isavuconazole orally ( n = 52; 53%) or intravenously ( n = 63; 64%) for an average of 12 days (IQR 5–23). For seven patients, no data were provided regarding the duration and dosage of isavuconazole and were therefore not considered in cost analyses. Notably, treatment regimens often evolved during hospitalisation. 47% of patients were treated with L-AmB and 31% received voriconazole after first-line treatment with isavuconazole during their hospital stay. While 31% ( n = 31) of the patients were treated exclusively with isavuconazole, 17% received all of the three antifungal agents during the observation period. Patients in the control group received exclusively L-AmB and voriconazole of which 32% ( n = 32) received both drugs. The durations of each antifungal therapy are shown in Table 2 for the whole study population, in Table S1 for the subgroup of patients with IA and in Table S2 for the subgroup of patients with IM.

Clinical effectiveness

Antifungal treatment was stopped at discharge in 36% ( n = 36) and 39% ( n = 39) in the isavuconazole and control group ( p = 0.451). The response to antifungal therapy was comparable between the two groups across all observation timepoints when comparing the total study population (Table 3 ). Data were most complete at day 14: 64% ( n = 47) of patients in the isavuconazole group and 70% ( n = 48) in the control group achieved at least stable clinical disease, whereas treatment failure occurred in 36% ( n = 26) and 29% ( n = 20) of patients, respectively ( p = 0.098). Since therapeutic drug monitoring (TDM) for isavuconazole is not routinely performed in clinical practice, sufficient data on this aspect could not be retrieved. TDM for voriconazole was performed in 8% ( n = 8) in the isavuconazole and 19% ( n = 19) in the voriconazole group. Among those patients, TDM was performed a median of four times in the isavuconazole group and three times in the control group. The median voriconazole drug levels were 1,000 mg/L (IQR 227–2,408) in the isavuconazole group and 2,246 mg/L (IQR 1,000–5,853, p < 0.001) in the control group. Only adverse events attributed to the treatment with isavuconazole by the responsible investigator were recorded. Those were observed in three patients (3%, n = 3), all of whom had to discontinue the treatment with isavuconazole subsequently. Documented adverse events were kidney dysfunction in the first, confusion and disorientation in the second, and erythema and facial oedema in the third patient.

Table 3 Response to antifungal treatment and outcome Isavuconazole group ( n = 99) Control group ( n = 99) p value Therapy response on day 14; n (%) 73 (74) 68 (69) 0.098 a Complete remission 6 (8) 9 (13) Partial remission 11 (15) 20 (29) Clinical stabilisation 30 (41) 19 (28) Therapy failure 26 (36) 20 (29) Therapy response on day 28; n (%) 49 (49) 43 (43) 0.976 a Complete remission 8 (16) 7 (16) Partial remission 15 (31) 13 (30) Clinical stabilisation 13 (27) 10 (23) Therapy failure 13 (27) 13 (30) Therapy response on day 42; n (%) 32 (32) 24 (24) 0.682 a Complete remission 8 (25) 4 (17) Partial remission 13 (41) 8 (33) Clinical stabilisation 6 (19) 6 (25) Therapy failure 5 (16) 6 (25) Therapy response on day 84; n (%) 15 (15) 13 (13) 0.317 b Complete remission 7 (47) 5 (39) Partial remission 8 (53) 5 (39) Clinical stabilisation 0 (0) 1 (8) Therapy failure 0 (0) 2 (15) End of therapy response; n (%) 26 (26) 34 (34) 0.563 b Complete remission 12 (46) 10 (29) Partial remission 1 (4) 3 (9) Clinical stabilisation 1 (4) 1 (3) Therapy failure 12 (46) 20 (59) Antifungal treatment stopped at discharge; n (%) 36 (36) 39 (39) 0.451 a Outcome; n (%) Regular discharge 63 (64) 58 (59) 0.411 a Transfer to other institution 6 (6) 10 (10) 0.307 a Death 29 (29) 31 (31) 0.793 a a Pearson chi-square test (two-tailed) b Fisher´s exact test

In-hospital mortality was similar in both groups (29%, n = 29 vs. 31%, n = 31, p = 0.793). Among the deceased, IM or IA was considered the reason of death in 21% ( n = 6) and 23% ( n = 7, p = 0.862). In patients with IM, mortality was notably lower in the isavuconazole group (15%, n = 2) compared to the control group (57%, n = 4, p = 0.052). For IA patients, approximately one third died during their hospital stay in both groups (32%, n = 28 vs. 29%, n = 27, p = 0.681).

A comparison of treatment durations and outcomes between case and control patients with IA (Table S1 and S3 ) and those with IM (Table S2 and S4 ), respectively, revealed no significant differences.

Hospitalisation and antifungal treatment costs

Direct cost factors, including hospitalisation and treatment costs, can be found in Table 4 . After adjusting to 2024 values, the hospital stay was the most expensive factor in both groups. Overall antifungal drug acquisition costs were significantly higher in the isavuconazole group, with an average cost difference of €9,588 per patient, compared to the control group. Notably, drug acquisition costs for voriconazole were significantly lower in the isavuconazole compared to the control group (€2,035, 95% CI €1,030-€3,309 vs. €5,551, 95% CI €3,519-€7,980, p = 0.002) With €49,042 (95% CI €42,475-€56,449), the overall treatment costs were significantly higher in the isavuconazole group compared to the control group with €39,369 (95% CI €34,437-€44,826, p = 0.030). Among the 31 patients treated exclusively with isavuconazole, mean drug acquisition costs per patient were at €9,532 (95% CI €5,335-€14,979).

Table 4 Costs for hospitalisation and treatment in Euro Isavuconazole group ( n = 99) Control group ( n = 99) p value a Hospitalisation costs I, b ; n (%) 91 (92) 86 (87) 0.249 d Costs per patient; Mean (95% CI) 30,440 (25,210 − 35,670) 31,528 (26,110 − 36,945) 0.781 Hospitalisation costs (Year 2024) Costs per patient; Mean (95% CI) 28,570 (24,592 − 32,548) 31,160 (26,238 − 36,083) 0.406 Antifungal drug acquisition costs c Costs per patient; mean (95% CI) Isavuconazole 10,785 (8,364 − 13,518) - - Liposomal Amphotericin B 9,689 (6,379 − 13,337) 7,250 (5,202-9,614) 0.253 Voriconazole 2,035 (1,030 − 3,309) 5,551 (3,519-7,980) 0.002** Overall antifungal drug acquisition costs c ; n (%) 90 (91) 82 (83) 0.092 d Costs per patient; Mean (95% CI) 22,389 (17,587 − 27,525) 12,801 (9,589 − 16,823) 0.003** Overall direct treatment costs I, b, c ; n (%) 91 (92) 86 (87) 0.249 d Costs per patient; Mean (95% CI) 50,912 (43,418 − 59,451) 39,736 (34,242 − 45,675) 0.026* Overall direct treatment costs (Year 2024) Costs per patient; Mean (95% CI) 49,042 (42,475 − 56,449) 39,369 (34,437 − 44,826) 0.030* Abbreviations: CI, Confidence Interval I n -values differ due to missing data a Bootstrapped t-test (independent samples, two sided) b Based on G-DRGs from 2016 to 2021 c Based on pharmacy retail prices from Rote Liste ® 2024 d Pearson chi-square test (two-tailed) * p -value < 0.05; ** p -value < 0.01

To identify cost differences among different IFDs, detailed cost analyses for patients with IA ( n = 180) and IM ( n = 20) were provided in Table S5 and Table S6 . Costs in IA patients were comparable to those observed in the total study population. Regarding the subgroup of patients with IM, hospitalisation costs remained similar, while drug acquisition costs and overall treatment costs were higher compared to the total study population. When regarding costs separated by classification of IFD, overall costs in the subgroup of patients with proven IFD were with €59,156 (95% CI 47,457 − 71,674) in the isavuconazole and €49,041 (95% CI 33,997 − 65,484) in the control group higher compared to the total study population and the subgroup of patients with IM ( p = 0.332) due to both higher hospitalisation and antifungal drug acquisition costs.

The GLM presented predictors influencing overall direct treatment costs for patients with IA and IM (Table 5 ). Intensive care treatment, a longer hospital LOS, as well as treatment with isavuconazole or L-AmB were independently associated with significantly higher overall direct treatment costs.

Table 5 Generalised linear model of variables influencing overall direct treatment costs of total study population Overall direct treatment costs Univariate GLM Multivariate GLM OR 95% CI p OR 95% CI p Age 0.992 0.985–0.999 0.033* 1.000 0.995–1.005 0.976 Sex (Reference = Male) Female 0.909 0.735–1.131 0.387 - - - Body Mass Index 1.000 0.977–1.024 0.995 - - - IFD (Reference = IA) IM 1.302 0.937–1.869 0.135 - - - Classification of IFD (Reference = Possible IFD) Probable IFD 1.323 1.056–1.653 0.015* 1.142 0.972–1.341 0.106 Proven IFD 1.579 1.168–2.159 0.004** 1.226 0.987–1.531 0.072 Acute kidney injury 1.059 0.835–1.359 0.643 Intensive care treatment 1.515 1.248–1.844 < 0.001*** 1.466 1.267–1.698 < 0.001*** Hospital LOS 1.012 1.009–1.014 < 0.001*** 1.010 1.008–1.013 < 0.001*** Isavuconazole treatment 1.316 1.085–1.596 0.006** 1.178 1.017–1.363 0.028* Liposomal Amphotericin B treatment 1.283 1.051–1.567 0.015* 1.243 1.074–1.438 0.004** Voriconazole treatment 1.166 0.956–1.421 0.131 Response to antifungal treatment on day 14 (Reference = Complete remission) Partial remission 0.720 0.443–1.139 0.172 - - - Clinical stabilisation 1.042 0.657–1.594 0.856 - - - Therapy failure 1.102 0.694–1.693 0.669 - - - Note: n = 174; Akaike information criterium: 3,910; Bayes information criterium: 3,939; deviation: 40.7; likelihood quotient chi-square: 116.5 ( p < 0.001) Abbreviations: CI, confidence interval; GLM, generalised linear model; IA, invasive aspergillosis; IFD, invasive fungal disease; IM, invasive mucormycosis; OR, Odds ratio * p value < 0.05; ** p -value < 0.01; *** p -value < 0.001

Discussion

In this retrospective case-control study, we analysed the clinical effectiveness and health economic impact of first-line treatment with isavuconazole in patients with IA and IM treated in tertiary care centres in Germany. While clinical outcomes such as the hospital LOS, mortality, and response to antifungal treatment were comparable between the two groups, drug acquisition costs and overall direct treatment costs were significantly higher in the isavuconazole group compared to the control group. Notably, overall treatment of patients with IM was about €12,100 and €4,300 more expensive compared to treatment of patients with IA in the case and control groups, respectively. The most significant cost drivers were intensive care treatment, the hospital LOS and initiating treatment with L-AmB and isavuconazole.

Previous studies found similar clinical outcomes in patients with IFD treated with isavuconazole compared to those treated with voriconazole and/or L-AmB [ 17 , 18 , 30 ]. In the SECURE trial, mortality rates at day 84 of 28% and 29% are comparable to our study results [ 17 ]. Moreover, treatment success rates (partial and complete) at the end of therapy of 35% and 36% are comparable to our findings with 50% and 38%, with a higher success rate in our isavuconazole-treated population [ 17 ]. The VITAL trial, which compared treatment with isavuconazole to L-AmB in IM patients, found mortality rates at day 42 of 33% and 41% ( p = 0.595) and complete and partial responses at the end of treatment of 14% and 17% in the total study population [ 18 ]. Based on patients enrolled in the SECURE trial, a prospective study from Horn et al. observed a shorter hospital LOS with a median of 13 and 15 days in the isavuconazole and voriconazole group compared to our study population (44 vs. 39 days) [ 31 ]. This is likely because our study population consisted exclusively of patients with haematological or oncological diseases requiring prolonged inpatient treatment for their underlying condition, whereas in the referenced study, only a proportion of patients had haematological malignancies. In the SECURE trial, the treatment durations in the intention-to-treat population were higher for isavuconazole and voriconazole, with a median of 45 (IQR 13–83) and 47 (IQR 13–83) days compared to our analysis with 12 (IQR 5–23) and 12 (IQR 4–29) days in the respective groups [ 17 ]. This may be due to treatment changes in cases of non-response. At day 14, 36% of patients in the isavuconazole group experienced therapy failure, resulting in a therapy switch to voriconazole or L-AmB. Less frequently, therapy changes were due to adverse events attributed to the treatment with isavuconazole in three patients. Additionally, the real-world design of our study may have contributed, as ongoing therapies could not always be continued following patient discharge. Nevertheless, we did not detect significant differences in therapy response between the two study groups.

These trials are characterised by a randomised-controlled study design, but real-world data on the clinical outcomes of IFD after treatment with isavuconazole remain limited. To date, few observational studies have been published that reported similar [ 32 ] or even better [ 33 ] clinical outcomes when treating IFDs with isavuconazole compared to other antifungal drugs. Other studies were only descriptive, focusing on clinical experience and adverse event rates of isavuconazole without comparison to other antifungal drugs [ 3 , 34 – 38 ]. Our study contributes new insights into the clinical effectiveness of isavuconazole compared to voriconazole or L-AmB in treating IFDs in a real-world, multicentre design.

In our study, hospitalisation costs for patients initiating first-line treatment with isavuconazole were comparable to those of patients treated with L-AmB and/or voriconazole. The economic model from Azanza et al. also indicated that hospitalisation costs were comparable in the groups, while drug acquisition costs and total costs were about €5,000 higher in the isavuconazole-treated group [ 21 ]. Their reported drug acquisition cost for isavuconazole (€12,883 per patient) was similar to our findings, while their cost for voriconazole (€7,644) was higher [ 21 ]. The economic analysis from Moya-Alarcón et al. described cost savings per patient treated with isavuconazole of €5,038 compared to treatment with liposomal L-AmB, which was attributed to a shorter duration in intravenous treatment [ 2 ]. Bagshaw et al. came to similar conclusions, reporting lower treatment costs of £3,770 or 20% in their groups (isavuconazole group: £14,842 per patient vs. L-AmB group: £18,612 per patient) [ 30 ]. When interpreting the results, it is important to consider that our study also included patients treated with voriconazole in the control group, which has substantially lower drug acquisition costs than isavuconazole and L-AmB. Besides L-AmB, which was plausibly identified as a cost driver in our GLM due to its high acquisition costs, our study confirms the high financial burden of isavuconazole treatment compared to generic voriconazole. This finding aligns with results from other studies and is largely driven by the drug’s ongoing patent protection [ 21 ].

Nevertheless, several studies have suggested that isavuconazole is cost-effective compared to voriconazole at a willingness-to-pay threshold (WPT) of €25,000/quality-adjusted life year (QALY) in Spain [ 21 ], $50,000 per death avoided in the United States [ 13 ] and £30,000/QALY in the United Kingdom [ 22 ]. The cost-effectiveness analysis from Azanza et al. conducted in Spain demonstrated that treatment with isavuconazole leads to 0.49 more life year gains (LY) and 0.41 more QALYs compared to treatment with voriconazole in patients with IA and IM [ 21 ]. Another study conducted in the United Kingdom came to similar conclusions (LYs = 0.48; QALYs = 0.39). In the deterministic sensitivity analyses from Harrington et al., isavuconazole was associated with lower total costs per treated patient than voriconazole, except for when the initial hospital LOS was increased by 25% in the isavuconazole group [ 13 ]. These results emphasise our findings in identifying hospital LOS as a key cost driver. Additionally, when focusing exclusively on patients treated with isavuconazole monotherapy in our study, mean antifungal drug acquisition costs per patient of €9,532 were lower compared to those who also received voriconazole and/or liposomal amphotericin B (€22,389). Consequently, overall antifungal drug acquisition costs in this subgroup were lower than those observed in the control group (€12,801).

Our findings demonstrated higher drug acquisition and overall treatment costs for IM patients compared to IA patients, suggesting that IM is more challenging to treat due to the difficulty in pathogen detection, which is compounded by non-specific symptoms and the rapid progression of disease [ 22 ]. Definite diagnosis of proven and probable cases requires direct sampling of infected tissue [ 23 ]. Consequently, the need for multiple diagnostic measures and the initiation of treatment before definitive diagnosis contribute to higher treatment costs [ 12 ]. Since the proportion of patients with proven IFD was higher in the isavuconazole group, costs were also expected to be higher. Heimann et al. compared direct treatment costs from patients with proven or probable IM to matched patients with similar underlying conditions based on G-DRGs in a cost-of-illness analysis [ 12 ]. They concluded that mean costs of patients with IM were significantly higher compared to those of matched patients (€53,261, 95% CI 39,660 − 68,825 vs. €20,269, 95% CI 14,707 − 26,653, p < 0.001). Antifungal drug acquisition costs for IM patients in their study were €22,819 (95% CI 15,036 − 32,346), which is slightly higher than the costs in our control group (€18,127, 95% CI 19,103 − 26,101). When interpreting these numbers, it should be noted that the study from Heimann et al. also considered treatment costs with posaconazole and caspofungin [ 12 ].

Our analysis is subject to important limitations. First, and most critically, the retrospective matching did not result in fully comparable cohorts. The isavuconazole group contained a significantly higher proportion of patients with ‘proven’ IFD (21% vs. 9%), introducing a strong potential for selection bias that likely confounds both clinical and cost comparisons. Second, our analysis compares treatment strategies, not just single drugs. The high rate of treatment switching means the costs attributed to the ‘isavuconazole group’ also include expensive subsequent therapies, making direct cost comparisons challenging. Third, our economic analysis was limited to the index hospitalisation and could not capture potential downstream cost savings from oral step-down therapy, a key feature of isavuconazole. Fourth, the inclusion of a large number of ‘possible’ IFD cases, who may not have had a fungal infection, likely diluted any true differences in treatment efficacy. Fifth, as this is a real-world study, data regarding TDM of voriconazole and isavuconazole were not comprehensively collected. It is reasonable to assume that TDM was performed more frequently in clinical practice. As TDM was not the primary focus of this study, this limitation has not influenced the main study outcomes. Finally, our findings are from the German inpatient setting and may not be generalizable to other health care systems.

In conclusion, our study found that a treatment strategy starting with isavuconazole was associated with higher overall treatment costs for IA and IM patients compared to treatment with L-AmB and/or voriconazole, while clinical outcomes were comparable. To our knowledge, this is the first study comparing treatment costs for IM patients to those of IA patients in a real-world inpatient setting in Germany. Clinical practice should focus on improving treatment strategies and early detection of IFD [ 18 ], especially in IM patients, to (i) decrease infection incidence, the hospital LOS, and mortality, and to (ii) reduce the identified cost drivers.

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary Material 1

Supplementary Material 2

Tables and Figures of Statistical Analysis by using R Studio version 4.5.0 (from 2025-04-11).

Marie Engelhard and Sebastian M. Wingen-Heimann contributed equally to this work.

J. Janne Vehreschild and Sina M. Pütz contributed equally to this work.

Author contributions

ME: writing – original draft, formal analysis. SMWH: writing – review & editing, conceptualization, investigation, methodology, project administration, funding acquisition. BG: writing - review & editing, investigation. MJGTV: writing - review & editing, investigation. JK: writing - review & editing, investigation. SE: writing - review & editing, investigation. KS: writing - review & editing, investigation. ES: writing - review & editing, investigation. BNB: writing - review & editing, Investigation. JJV: writing – original draft, conceptualization, investigation, methodology, supervision. SMP: writing – original draft, conceptualization, investigation, methodology, formal analysis, project administration, funding acquisition.

Funding

Open Access funding enabled and organized by Projekt DEAL. This study was supported by an unrestricted research grant from Pfizer Pharma GmbH, 10785 Berlin, Germany. It was designed, planned, and performed by the academic authors of the University Hospital Cologne, Germany.

Data availability

The authors are not permitted to disclose the study data beyond the research team. However, the data can be accessed through direct request to the corresponding author, and R scripts used to analyse the data can be made available on reasonable request.

Declarations

Ethics approval

A primary ethics vote was obtained at the Ethics Committee of the Department of Medicine at the University of Cologne on 2021-06-22 (local ethics ID approval 21–1369-retro), as the University Hospital Cologne was the leading study site. The participating study site received their local ethics vote at the respective ethics commission.

Competing interests

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ME has received travel grants from Tillotts and Pfizer. SMWH has received research and travel grants from Astellas, MSD, and Tillotts; research grants from Basilea, Gilead, and 3 M; travel grants from Pfizer, and lecture honoraria from Astellas, MSD, and Tillotts. MJGTV has received research grants from MSD, Heel, Roche, Tillotts, and consulting fees from GILEAD, Tillotts, Pfizer, Bioaster, GSK, Ecraid, and meeting and travel support from Akademie für Infektionsmedizin, Astra Zeneca, bioMerieux, DGI, European Society of Neurogastroenterology, Falk Foundation, FomF GmbH, GILEAD, GSK, Helios Kliniken, Hessisches Landessozialgericht, Infektio Forum, Janssen Cilag GmbH, Klinikum Kassel, Landesärztekammer Hessen, LMU Kliniken, MSD, Pfizer, Streamed up, St. Vincent Hospital, Tillotts. JK has received organisation and speaker fees from Landesärztekammer Hessen. SE has received speaker honoraria from Gilead. KS received speaker honoraria and/or travel grants by and/or has been consultant to Abbvie, Alexa, Bristol Myers Squibb, Jazz Pharmaceuticals, Leo, Pfizer, Sanofi, Servier, Sobi, Stemline, Takeda, MSD, Gilead. BNB received speaker honoraria, travel grants and has consulted to Beigene, Gilead, Jazz Pharmaceuticals, Bristol Myers Squibb, Incyte, Janssen Cilag. JJV received research grants from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zentrum für Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, German Network University Medicine, German Cancer Consortium (DKTK), German Federal Ministry of Health (BMG), European Union, speaker fees from MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Centre for Infection Research (DZIF), University Hospital Freiburg/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), Ärztekammer Nordrhein, Ärztekammer Hessen, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universitätsmedizin, Janssen, NordForsk, Biontech, APOGEPHA, German Cancer Consortium (DKTK), University Hospital Oldenburg, and meeting and travel support from German Centre for Infection Research (DZIF), University Manchester, German Society for Infectious Diseases (DGI), University Hospital Aachen, German Society for Internal Medicine (DGIM), Netzwerk Universitätsmedizin, German Cancer Consortium (DKTK). SMP received travel grants and lecture honoraria from Tillotts. BG and ES have no conflicts of interest.

References

1. Kably B Antifungal drugs TDM: trends and update Ther Drug Monit 2022 44 1 166 97 10.1097/FTD.0000000000000952 34923544 Kably B, et al. Antifungal drugs TDM: trends and update. Ther Drug Monit. 2022;44(1):166–97. 34923544 10.1097/FTD.0000000000000952

2. Moya-Alarcón C Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain Expert Rev Anti Infect Ther 2024 22 8 713 20 10.1080/14787210.2024.2327517 38494912 Moya-Alarcón C, et al. Economic impact of managing invasive mold disease with isavuconazole compared with liposomal amphotericin B followed by posaconazole in Spain. Expert Rev Anti Infect Ther. 2024;22(8):713–20. 38494912 10.1080/14787210.2024.2327517

3. Jeck J Health economic analysis of patients treated with isavuconazole in a German comprehensive cancer centre Mycoses 2023 66 5 405 11 10.1111/myc.13567 36670539 Jeck J, et al. Health economic analysis of patients treated with isavuconazole in a German comprehensive cancer centre. Mycoses. 2023;66(5):405–11. 36670539 10.1111/myc.13567

4. Lass-Flörl C Steixner S The changing epidemiology of fungal infections Mol Aspects Med 2023 94 101215 10.1016/j.mam.2023.101215 37804792 Lass-Flörl C, Steixner S. The changing epidemiology of fungal infections. Mol Aspects Med. 2023;94:101215. 37804792 10.1016/j.mam.2023.101215

5. Roden MM Epidemiology and outcome of zygomycosis: a review of 929 reported cases Clin Infect Dis 2005 41 5 634 53 10.1086/432579 16080086 Roden MM, et al. Epidemiology and outcome of zygomycosis: a review of 929 reported cases. Clin Infect Dis. 2005;41(5):634–53. 16080086 10.1086/432579

6. Zilberberg MD Epidemiology and outcomes of hospitalizations with invasive aspergillosis in the united States, 2009–2013 Clin Infect Dis 2018 67 5 727 35 10.1093/cid/ciy181 29718296 PMC7190884 Zilberberg MD, et al. Epidemiology and outcomes of hospitalizations with invasive aspergillosis in the United States, 2009–2013. Clin Infect Dis. 2018;67(5):727–35. 29718296 10.1093/cid/ciy181 PMC7190884

7. Skiada A Zygomycosis in europe: analysis of 230 cases accrued by the registry of the European confederation of medical mycology (ECMM) working group on zygomycosis between 2005 and 2007 Clin Microbiol Infect 2011 17 12 1859 67 10.1111/j.1469-0691.2010.03456.x 21199154 Skiada A, et al. Zygomycosis in europe: analysis of 230 cases accrued by the registry of the European Confederation of Medical Mycology (ECMM) Working Group on Zygomycosis between 2005 and 2007. Clin Microbiol Infect. 2011;17(12):1859–67. 21199154 10.1111/j.1469-0691.2010.03456.x

8. Jenks JD Mehta SR Hoenigl M Broad spectrum Triazoles for invasive mould infections in adults: which drug and when? Med Mycol 2019 57 Supplement2 S168 78 10.1093/mmy/myy052 30816967 Jenks JD, Mehta SR, Hoenigl M. Broad spectrum triazoles for invasive mould infections in adults: which drug and when? Med Mycol. 2019;57(Supplement2):S168–78. 30816967 10.1093/mmy/myy052

9. Heimann SM Intravenous and tablet formulation of posaconazole in antifungal therapy and prophylaxis: A retrospective, non-interventional, multicenter analysis of hematological patients treated in tertiary-care hospitals Int J Infect Dis 2019 83 130 8 10.1016/j.ijid.2019.04.006 30978465 Heimann SM, et al. Intravenous and tablet formulation of posaconazole in antifungal therapy and prophylaxis: a retrospective, non-interventional, multicenter analysis of hematological patients treated in tertiary-care hospitals. Int J Infect Dis. 2019;83:130–8. 30978465 10.1016/j.ijid.2019.04.006

10. Reid G Mucormycosis Semin Respir Crit Care Med 2020 41 1 99 114 10.1055/s-0039-3401992 32000287 Reid G, et al. Mucormycosis. Semin Respir Crit Care Med. 2020;41(1):99–114. 32000287 10.1055/s-0039-3401992

11. Seidel D FungiScope(™) -Global emerging fungal infection registry Mycoses 2017 60 8 508 16 10.1111/myc.12631 28730644 Seidel D, et al. FungiScope(™) -global emerging fungal infection registry. Mycoses. 2017;60(8):508–16. 28730644 10.1111/myc.12631

12. Heimann SM 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 J Hosp Infect 2019 101 3 339 46 10.1016/j.jhin.2018.11.003 30423409 Heimann SM, et al. 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. J Hosp Infect. 2019;101(3):339–46. 30423409 10.1016/j.jhin.2018.11.003

13. Harrington R Cost-Effectiveness analysis of isavuconazole vs. Voriconazole as First-Line treatment for invasive aspergillosis Adv Ther 2017 34 1 207 20 10.1007/s12325-016-0443-1 27913989 PMC5216061 Harrington R, et al. Cost-effectiveness analysis of isavuconazole vs. Voriconazole as First-Line treatment for invasive aspergillosis. Adv Ther. 2017;34(1):207–20. 27913989 10.1007/s12325-016-0443-1 PMC5216061

14. Skiada A Challenges in the diagnosis and treatment of mucormycosis Med Mycol 2018 56 suppl1 93 101 10.1093/mmy/myx101 29538730 PMC6251532 Skiada A, et al. Challenges in the diagnosis and treatment of mucormycosis. Med Mycol. 2018;56(suppl1):93–101. 29538730 10.1093/mmy/myx101 PMC6251532

15. Lewis JS New perspectives on antimicrobial agents: isavuconazole Antimicrob Agents Chemother 2022 66 9 e0017722 10.1128/aac.00177-22 35969068 PMC9487460 Lewis JS 2, et al. New perspectives on antimicrobial agents: isavuconazole. Antimicrob Agents Chemother. 2022;66(9):e0017722. 35969068 10.1128/aac.00177-22 PMC9487460

16. Seyedmousavi SR, Ilkit H, Tolooe M, Hedayati A, Verweij MT. P. Systemic Antifungal Agents: Current Status and Projected Future Developments , in Human Fungal Pathogen Identification. Methods in Molecular Biology , T. Lion, Editor. 2017. pp. 107–139. 10.1007/978-1-4939-6515-1_5 27837500

17. Maertens JA Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial Lancet 2016 387 10020 760 9 10.1016/S0140-6736(15)01159-9 26684607 Maertens JA, et al. Isavuconazole versus voriconazole for primary treatment of invasive mould disease caused by Aspergillus and other filamentous fungi (SECURE): a phase 3, randomised-controlled, non-inferiority trial. Lancet. 2016;387(10020):760–9. 26684607 10.1016/S0140-6736(15)01159-9

18. Marty FM Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis Lancet Infect Dis 2016 16 7 828 37 10.1016/S1473-3099(16)00071-2 26969258 Marty FM, et al. Isavuconazole treatment for mucormycosis: a single-arm open-label trial and case-control analysis. Lancet Infect Dis. 2016;16(7):828–37. 26969258 10.1016/S1473-3099(16)00071-2

19. Desai AV et al. Exposure-response relationships for isavuconazole in patients with invasive aspergillosis and other filamentous fungi. Antimicrob Agents Chemother. 2017;61(12). 10.1128/AAC.01034-17 PMC5700339 28923872

20. Floros L Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden BMC Infect Dis 2019 19 1 134 10.1186/s12879-019-3683-2 30744563 PMC6371439 Floros L, et al. Cost-effectiveness analysis of isavuconazole versus voriconazole for the treatment of patients with possible invasive aspergillosis in Sweden. BMC Infect Dis. 2019;19(1):134. 30744563 10.1186/s12879-019-3683-2 PMC6371439

21. Azanza JR The cost-effectiveness of isavuconazole compared to voriconazole, the standard of care in the treatment of patients with invasive mould diseases, prior to differential pathogen diagnosis in Spain Mycoses 2021 64 1 66 77 10.1111/myc.13189 32989796 PMC7894146 Azanza JR, et al. The cost-effectiveness of isavuconazole compared to voriconazole, the standard of care in the treatment of patients with invasive mould diseases, prior to differential pathogen diagnosis in Spain. Mycoses. 2021;64(1):66–77. 32989796 10.1111/myc.13189 PMC7894146

22. Floros L The cost-effectiveness of isavuconazole compared to the standard of care in the treatment of patients with invasive fungal infection prior to differential pathogen diagnosis in the united Kingdom J Med Econ 2020 23 1 86 97 10.1080/13696998.2019.1638789 31262225 Floros L, et al. The cost-effectiveness of isavuconazole compared to the standard of care in the treatment of patients with invasive fungal infection prior to differential pathogen diagnosis in the United Kingdom. J Med Econ. 2020;23(1):86–97. 31262225 10.1080/13696998.2019.1638789

23. De Pauw B Revised definitions of invasive fungal disease from the European organization for research and treatment of Cancer/Invasive fungal infections cooperative group and the National Institute of allergy and infectious diseases mycoses study group (EORTC/MSG) consensus group Clin Infect Dis 2008 46 12 1813 21 10.1086/588660 18462102 PMC2671227 De Pauw B, et al. Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis. 2008;46(12):1813–21. 18462102 10.1086/588660 PMC2671227

24. von Elm E The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies Lancet 2007 370 9596 1453 7 10.1016/S0140-6736(07)61602-X 18064739 von Elm E, et al. The strengthening the reporting of observational studies in epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. 18064739 10.1016/S0140-6736(07)61602-X

25. Husereau D Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations Value Health 2022 25 1 3 9 10.1016/j.jval.2021.11.1351 35031096 Husereau D, et al. Consolidated health economic evaluation reporting standards 2022 (CHEERS 2022) statement: updated reporting guidance for health economic evaluations. Value Health. 2022;25(1):3–9. 35031096 10.1016/j.jval.2021.11.1351

26. von der Graf JM German recommendations on health economic evaluation: third and updated version of the Hanover consensus Value Health 2008 11 4 539 44 10.1111/j.1524-4733.2007.00301.x 18194408 von der Graf JM, et al. German recommendations on health economic evaluation: third and updated version of the Hanover consensus. Value Health. 2008;11(4):539–44. 18194408 10.1111/j.1524-4733.2007.00301.x

27. Drummond MF, et al. Methods for the economic evaluation of health care programmes. Oxford University Press; 2015.

28. InEK - Institut für das Entgeltsystem im Krankenhaus . 2025 [cited 2025; Available from: https://www.g-drg.de/

29. Arzneimittelinformation für. Deutschland . 2025; Available from: https://www.rote-liste.de/

30. Bagshaw E The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK Future Microbiol 2017 12 515 25 10.2217/fmb-2016-0231 28191796 Bagshaw E, et al. The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK. Future Microbiol. 2017;12:515–25. 28191796 10.2217/fmb-2016-0231

31. Horn D Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial J Med Econ 2016 19 7 728 34 10.3111/13696998.2016.1164175 26960060 Horn D, et al. Hospital resource use of patients receiving isavuconazole vs voriconazole for invasive mold infections in the phase III SECURE trial. J Med Econ. 2016;19(7):728–34. 26960060 10.3111/13696998.2016.1164175

32. Batista MV et al. Comparing the real-world use of isavuconazole to other anti-fungal therapy for invasive fungal infections in patients with and without underlying disparities: a multi-center retrospective study. J Fungi (Basel). 2023;9(2). 10.3390/jof9020166 PMC9958690 36836281

33. Qin J et al. Real-World effectiveness and safety of isavuconazole versus amphotericin B for patients with invasive mucormycosis. Microorganisms, 2025. 13(1). 10.3390/microorganisms13010055 PMC11767576 39858823

34. Dagher H et al. Real-world use of isavuconazole as primary therapy for invasive fungal infections in high-risk patients with hematologic malignancy or stem cell transplant. J Fungi (Basel). 2022;8(1). 10.3390/jof8010074 PMC8779319 35050014

35. Neofytos D Effectiveness, Safety, and patterns of Real-World isavuconazole use in Europe (2015–2019) Infect Dis Ther 2024 13 12 2527 43 10.1007/s40121-024-01064-4 39443403 PMC11582280 Neofytos D, et al. Effectiveness, safety, and patterns of real-world isavuconazole use in Europe (2015–2019). Infect Dis Ther. 2024;13(12):2527–43. 39443403 10.1007/s40121-024-01064-4 PMC11582280

36. Hassouna H Athans V Brizendine KD Real-world use-Isavuconazole at a large academic medical center Mycoses 2019 62 6 534 41 10.1111/myc.12910 30851214 Hassouna H, Athans V, Brizendine KD. Real-world use-isavuconazole at a large academic medical center. Mycoses. 2019;62(6):534–41. 30851214 10.1111/myc.12910

37. Kwon M Real-World experience with isavuconazole in allogeneic stem cell transplantation in Spain Transpl Cell Ther 2024 30 10 1033 10.1016/j.jtct.2024.06.009 38871055 Kwon M, et al. Real-world experience with isavuconazole in allogeneic stem cell transplantation in Spain. Transpl Cell Ther. 2024;30(10):1033.e1-1033.e8. 10.1016/j.jtct.2024.06.009 38871055

38. Ergün M Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study J Antimicrob Chemother 2024 79 8 1801 10 10.1093/jac/dkae139 38935893 PMC11290874 Ergün M, et al. Isavuconazole as prophylaxis and therapy for invasive fungal diseases: a real-life observational study. J Antimicrob Chemother. 2024;79(8):1801–10. 38935893 10.1093/jac/dkae139 PMC11290874