Isavuconazole is a new broad-spectrum antifungal triazole with a better safety profile in terms of drug–drug interactions, adverse effects, and tolerance compared to other azoles. Increasing evidence supports the usefulness of isavuconazole in the treatment of invasive fungal diseases. In this review, we aim to analyze the influence of this new evidence on the main clinical guidelines. We reviewed the most recent consensus guidelines issued by the major infectious diseases societies worldwide, focusing on the novelties regarding the recommendations for the use of isavuconazole in different invasive fungal infections and management strategies.
Isavuconazole has been included as first-line therapy for invasive aspergillosis, with slight differences in preference for voriconazole or isavuconazole depending on the clinical scenario. In mucormycosis, isavuconazole is considered an alternative first-line therapy to liposomal amphotericin B, especially in those patients with underlying renal impairment. Additionally, the use of isavuconazole is suggested in salvage scenario for both conditions, and the combination with other mold-active drugs is considered. The guidelines report the promising results obtained with the use of this drug for treating mycoses caused by other molds and rare yeasts, as well as endemic mycoses, but since solid evidence is still lacking, the recommendations in this area are generally weak.
Isavuconazole is a suitable therapeutic option for invasive fungal infections, offering efficacy against a range of pathogens, including Aspergillus and fungi within the order Mucorales. Its safety profile and its favorable drug interaction profile make it a valuable alternative to traditional agents like voriconazole or liposomal amphotericin B in certain scenarios. However, continued research is essential to better understand its role in combination therapies and to assess its effectiveness against other fungal species.
El isavuconazol es un nuevo antifúngico triazólico de amplio espectro con un mejor perfil de seguridad en términos de interacciones farmacológicas, efectos adversos y tolerancia en comparación con otros azoles. Cada vez existe más evidencia que apoya la utilidad del isavuconazol en el tratamiento de la enfermedad fúngica invasiva. En esta revisión se pretende analizar la influencia de estas nuevas evidencias en las principales guías clínicas. Se revisan las guías de consenso más recientes emitidas por las principales sociedades de enfermedades infecciosas a nivel mundial, enfocando las novedades en cuanto a las recomendaciones para el uso de isavuconazol en diferentes infecciones fúngicas invasivas y en las estrategias de manejo.
El isavuconazol se ha incluido como tratamiento de primera línea de la aspergilosis invasiva, con ligeras diferencias en la preferencia por voriconazol o isavuconazol dependiendo del escenario clínico. En la mucormicosis, el isavuconazol se considera un tratamiento de primera línea alternativo a la anfotericina B liposomal, especialmente en aquellos pacientes con insuficiencia renal subyacente. Además, se sugiere el uso de isavuconazol en situaciones de rescate de ambas entidades clínicas, y se considera la combinación con otros fármacos activos frente a hongos. Las pautas reconocen los resultados prometedores obtenidos con el uso de este antifúngico para el tratamiento de infecciones fúngicas por otros hongos y levaduras raras, y de micosis endémicas. No obstante, aún faltan evidencias sólidas, por lo que las recomendaciones en esta área son generalmente débiles.
El isavuconazol es una opción terapéutica adecuada para las infecciones fúngicas invasivas y eficaz contra una variedad de patógenos, incluidos Aspergillus y hongos del orden Mucorales. Su rango de seguridad y su favorable perfil de interacción farmacológica lo convierten en una alternativa valiosa frente a los fármacos antifúngicos tradicionales, como el voriconazol o la anfotericina B liposomal, en ciertos escenarios. Sin embargo, es esencial continuar la investigación para comprender mejor su papel en terapias combinadas y evaluar su efectividad contra otras especies de hongos.
Since the Food and Drug Administration in the United States approved isavuconazole for the treatment of invasive aspergillosis (IA) in 2016, it has been progressively incorporated into the clinical practice given its favorable profile of adverse effects, the more predictable pharmacokinetics, and its limited spectrum of drug interactions. The evidence favoring the use of this antifungal is increasing, and the majority of published clinical guidelines regarding invasive fungal disease have included isavuconazole into the antifungal armamentarium. Some of them have already included it as first-line treatment, at the same level of evidence as voriconazole. However, many guidelines still consider isavuconazole a second-line option compared to conventional treatment, generally voriconazole, posaconazole or liposomal amphotericin B (L-AmB), due to the broader clinical experience with these antifungals. Invasive aspergillosis is the main clinical scenario where isavuconazole is being used, but patients with other infections such as mucormycosis, other less frequent infections by molds or rare yeasts, or endemic mycoses, are likely to benefit from this antifungal. Herein we review the specific considerations of the main clinical guidelines for invasive fungal disease regarding the recommendations for the use of isavuconazole.
1MethodA comprehensive review of the major clinical guidelines for invasive fungal infections (IFI), the guidelines from leading medical and infectious disease organizations specifically, including the Infectious Diseases Society of America (IDSA), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), the ECIL (European Conference on Infections in Leukemia) guidelines, the Australasian guidelines for the management of IFI, and other relevant national or international societies was conducted. The recommendations were categorized according to the assessments provided in the respective clinical guidelines, considering the strength of recommendation (grade A: strong; B: moderate; and C: weak or marginal recommendation) and the quality of evidence supporting them (I: at least one randomized, controlled trial supporting the recommendation being made; II: at least one well-designed clinical trial without randomization, or from cohort or case-controlled studies; and III: expert opinions based on clinical experience or descriptive case studies). The review focuses on the recommended use of isavuconazole in the treatment of various IFI, including IA, mucormycosis, and other invasive fungal infections. In addition, data from pivotal clinical trials evaluating isavuconazole were included to provide context on the drug's role in the current antifungal therapy.
2Invasive aspergillosisSince the introduction of mold-active azole drugs, the treatment of IA has notably evolved. Amphotericin B was replaced by voriconazole as first-line agent following a randomized trial in which voriconazole demonstrated superior efficacy and better survival at 12 weeks (71% vs. 58%) and a higher rate of response (55% vs. 38%) with less side effects than amphotericin B.17 Notably, voriconazole showed better outcomes in neutropenic and allogenic stem cell transplantation recipients. Although in this study the comparative agent was amphotericin B deoxycholate (d-AmB) with a high discontinuation rate, the median duration of treatment with this drug was 10 days, subsequent studies have confirmed the efficacy of voriconazole compared to amphotericin B for the treatment of IA.12,27
In the SECURE trial, where isavuconazole was compared to voriconazole to treat IA in hematologic patients, similar all-cause mortality rates were reported: 19% for isavuconazole vs. 20% for voriconazole. However, isavuconazole demonstrated a better safety profile, with fewer discontinuations (8% vs. 14%).22 Following this trial, the main clinical guidelines have included isavuconazole among the treatment options for IA, though the strength of recommendation and level of evidence vary depending on the specific patient scenario and the publication year of the consensus (as appreciated in Table 1), reflecting the growing experience and data on the use of isavuconazole.10,13,19,29,38,39
Summary of recommendations for the treatment of invasive aspergillosis.
| Clinical context | First line | Second line | Guideline |
|---|---|---|---|
| General consideration | Voriconazole (AI) | Isavuconazole and L-AmB (AII) | IDSA 2016 (5) |
| Voriconazole 1st option (AI)Isavuconazole or posaconazole (AI) as alternative 1st-line options | AmB (AII) | Australasian 2020 (10) | |
| Hematological patients | Isavuconazole or voriconazole (AI) | L-AmB (AII) | ECIL 2017 (6)European 2018 (7)SEIMC 2019 (8) |
| SOT and non-hematological patients | Voriconazole (AII) | L-AmB (AII-AIII) | European 2018 (7)SEIMC 2019 (8) |
| Voriconazole (AI) | Isavuconazole or AmB (particularly if liver insufficiency) (AII) | American transplant 2020 (9) | |
| Pediatrics | Voriconazole (AI)Isavuconazole (AII)L-AmB* (AII, AIII, BI and BII),particularly for <2-year-old | AmB (BI) | SEIMC 2019 (8) ECIL-8 2020 (12), Australasian 2020 (10)IDSA 2016 (5) |
| AmB (BI) | ECIL-8 2020 (12) | ||
| ICU setting | Voriconazole (BII) | Isavuconazole (BII) (particularly if renal insufficiency) | SEIMC 2019 (8) |
| Extrapulmonary | Voriconazole (AII-AIII) | L-AmB (AII-AIII) | SEIMC 2019 (8) European 2019 (7) |
| Salvage therapy/breakthrough IA | TDM, switching antifungal class or combination, nebulized, reduce immunosuppression. Isavuconazole, posaconazole, L-AmB | IDSA 2016 (5)SEIMC 2019 (8)Australasian 2020 (10) | |
IA: invasive aspergillosis; L-AmB: liposomal amphotericin B; AmB: amphotericin B; SOT: solid organ transplantation; ICU: intensive care unit; TDM: therapeutic drug monitoring; IDSA: Infectious Diseases Society of America; ESCMID: European Society of Clinical Microbiology and Infectious Diseases; ECIL: European Conference on Infections in Leukemia; SEIMC: Infectious Diseases and Clinical Microbiology Spanish Society.
IDSA guidelines, published in 2016, still consider isavuconazole a second-line option (AII: strong recommendation, moderate-quality of evidence).29 They recommend voriconazole as the primary treatment (AI; strong recommendation, high-quality evidence). Treatment with L-AmB or isavuconazole are considered alternative options (AII; strong recommendation, moderate-quality evidence). This more favorable recommendation for voriconazole is based on the favorable results of voriconazole over d-AmB, as well as the greater clinical experience accumulated with voriconazole at the time of publication, shortly after the SECURE trial.17,22 Regarding isavuconazole, the guidelines note that it demonstrated non-inferiority to voriconazole in the treatment of IA in the SECURE trial, showing similar survival and treatment response outcomes, regardless of diagnostic certainty and with fewer drug-related adverse effects, particularly in hepatobiliary, eye and skin disorders (Table 1).
ECIL-6 guidelines, published in 2017, recommends either voriconazole or isavuconazole (AI) as first-line treatment for IA in patients with hematological malignancies (Table 1), considering them equally effective, with isavuconazole offering a better safety profile.38
The ESCMID and the European Respiratory Society Joint Clinical (ESCMID-ECMM-ERS) guideline, and the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC, by its Spanish acronym) guidelines provide specific considerations for different patient groups.13,39 For the treatment of IA in hematological patients (hematological malignancy or stem cell transplantation), isavuconazole is recommended as first-line treatment, alongside with voriconazole (AI). However, for the treatment of IA in patients without hematological malignancies, particularly in solid organ transplant (SOT) recipients, voriconazole is recommended as first-line treatment (AII) due to the lack of clinical data on isavuconazole for this patient group at the time of the guideline's publication (as observed in Table 1). The guidelines emphasize the need to individualize treatment, taking into account the type of transplant, the immunosuppressive therapy, and the severity of IA. Therapeutic drug monitoring is recommended when a treatment with voriconazole is started given its potential drug–drug interactions and toxicity. If hepatotoxicity or concerns about drug interactions arise, a lipid formulation, such as L-AmB, is suggested, with careful consideration of the potential nephrotoxicity. The guidelines also report the lack of clinical experience with isavuconazole for treating IA in transplant patients at the time of publication.
However, in the context of SOT, the more recent guidelines of the American Society of Transplantation Infectious Diseases Community of Practice include isavuconazole, as well as L-AmB as alternative option to voriconazole, which remains the first-line treatment.19 This marks the first consensus to include isavuconazole for the treatment option for IA in SOT recipients (as stated in Table 1).
Finally, the Australasian guidelines, published in 2021, recommend voriconazole as the first-line therapy for IA in patients not receiving anti-mold prophylaxis (AI). However, isavuconazole is considered a reasonable first-line option, particularly in cases of severe and prolonged immunosuppression where there is concern about coinfection with more than one fungus.10 A recently published trial comparing posaconazole to voriconazole as first-line therapy for IA demonstrated the non-inferiority of posaconazole in terms of mortality and global clinical response, with better tolerance compared to voriconazole.23 Based on this evidence, the Australasian guidelines include posaconazole as an alternative first-line agent (AI).10
For paediatric patients, although isavuconazol is not yet approved, a provisional grade A recommendation with level II evidence, contingent upon regulatory approval by the European Medicine Agency, has been provided.14
Regarding combination therapy, all guidelines agree that it should not be generally recommended as the primary treatment for IA (CIII; weak recommendation, low level of evidence).10,13,19,29,38,39
In hematologic patients, the only combination regimen that has shown positive results is voriconazole plus anidulafungin, observed in a selected subset of patients with positive galactomannan tests. Mortality rates were 15.7% for the combination therapy compared to 27.3%, voriconazole monotherapy.23 Based on this study, the IDSA and ECIL-6 guidelines recommend considering this combination in cases of documented IA and severe disease, particularly in patients with hematologic malignancies or profound and persistent neutropenia (CII). However, the study failed to achieve its primary endpoint of reduced all-cause mortality at week 6, with rates of 19.3% for combination therapy and 27.5% for monotherapy (difference of −8.2% in favor of combination therapy, p=0.087).24 In contrast, the European and the SEIMC guidelines upgrade the recommendation for this combination to CI, despite acknowledging the study's failure to meet the primary endpoint. The European guidelines, in particular, emphasizes the critical role of therapeutic drug monitoring.13,39
In SOT recipients, the combination of voriconazole and caspofungin failed to obtain improved 90-day survival compared to a historical cohort treated with L-AmB monotherapy. However, in the subgroup of patients with renal failure or IA caused by Aspergillus fumigatus, this combination was independently associated with reduced mortality.34 As a result, the European and SEIMC guidelines recommend this therapy with a BII level of recommendation.13,39 Additionally, both the SEIMC and the American Transplantation Society suggest initiating antifungal combination therapy in severe forms of IA, such as central nervous system (CNS) involvement or disseminated disease, at least until therapeutic concentrations of voriconazole are achieved. In case of CNS involvement, echinocandins should be avoided due their limited ability to cross the blood–brain barrier. Isavuconazole is not mentioned at this point due to the lack of experience with its use in the combination therapy. However, given its favorable safety profile and lower rate of drug–drug interactions, it could be considered an alternative when other azoles are not suitable due to concerns about interactions.
2.1Salvage therapy and breakthrough IAAn individualized approach is recommended, taking into account the rapidity, severity, and extent of infection, patient comorbidities, and the exclusion of other emerging pathogens (AIII; strong recommendation; low-quality evidence).29 The general management strategy includes therapeutic drug monitoring, switching to a different class of antifungal or using combination therapy (CII), administration of antifungals by nebulized aerosol route when possible, tapering or reversing underlying immunosuppression when feasible (Table 1), performing susceptibility testing on any Aspergillus isolates (clinically significant) recovered from the patient, and resecting accessible lesions.10,29,39
At this point, isavuconazole is included among the potential salvage agents for IA if not used in primary therapy, alongside with L-AmB, posaconazole, itraconazole, and the echinocandins caspofungin and micafungin.13,29 While the limited experience with isavuconazole is recognized, it may be a reasonable option for patients currently receiving a different azole and experiencing adverse effects, such as prolonged QT interval, which is less likely to occur with isavuconazole therapy (it may rather cause a shortening of the QT interval). In the more recent guidelines of the Australasian committee, a switch to isavuconazole is recommended in cases of suspected breakthrough IA occurring under voriconazole, posaconazole or, particularly, L-AmB therapy.10
2.2Invasive aspergillosis in the ICU settingVoriconazole is the first-line antifungal agent for critically ill patients with IA (BII) as it has been identified as an independent variable associated with improved survival in hematology patients requiring mechanical ventilation.5 Isavuconazole is considered a reasonable alternative (BII) due to the better tolerance and cyclodextrin-free formulation, which eliminates concerns about its use in patients with severe renal dysfunction (Table 1). While the limited clinical experience with isavuconazole in this scenario is acknowledged, its ability to achieve high concentrations in the lungs is of significant interest.13
2.3Extrapulmonary and central nervous system IAVoriconazole and L-AmB are the primary options for the treatment of extrapulmonary IA.13,39 Surgical intervention should be pursued if the lesions are accessible. For CNS-IA, voriconazole constitutes the standard of treatment due to its small molecular size, which allows an adequate diffusion into the CNS. L-AmB is considered the best alternative (AIII). The combination of voriconazole and L-AmB may also be considered, as it has demonstrated superiority over other combinations or monotherapy (CIII).13,32 Isavuconazole is not included in this scenario due to insufficient evidence supporting its use.13 The diffusion of isavuconazole into the CNS reaches a maximum concentration (Cmax) in cerebrospinal fluid (CSF) obtained by lumbar puncture of 30% in comparison to the serum Cmax; this concentration is considerably lower than that reached by voriconazole, which is equal to or greater than 50%.21,31,33 The concentration of isavuconazole may be almost undetectable or null when determined in intraventricular CSF or in brain abscesses, although it is known to reach the brain parenchyma.
3Non-Aspergillus molds3.1MucormycosisThere is strong consensus on the need for surgical intervention in mucormycosis whenever possible, in addition to administering systemic antifungal treatment. L-AmB (5–10mg/kg per day) is the first-line antifungal treatment for mucormycosis (AII).4,9 However, following the positive and favorable outcomes of the VITAL study, isavuconazole is considered an alternative first-line therapy (AII, per the Global guideline and BII per the Australasian guideline; Table 2), particularly for patients with underlying renal impairment.9,4,25 The VITAL trial matched 21 patients with proven or probable mucormycosis treated with isavuconazole as primary therapy with 33 external controls from the FungiScope registry who received L-AmB.25 Complete or partial response at the end of treatment occurred in 32% (6/19) of patients in the isavuconazole group. Crude all-cause mortality at day 42 was 33% (7/21) for the isavuconazole group, compared to 39% (13/33) in the matched control group.
Summary of recommendations for the treatment of mucormycosis and other rare fungal invasive diseases.a
| Microorganism/Fungal infection | First line | Alternative/second line |
|---|---|---|
| Mucormycosis | L-AmB or isavuconazole (AII)* | Posaconazole (BII)Isavuconazole (BII)*Combination therapy (BIII) |
| Scedosporium spp. | Voriconazole (AII) | L-AmB+voriconazole (B)Isavuconazole (C) |
| Lomentospora prolificans | Voriconazole+terbinafine (AIII) | Voriconazole +/− another antifungal (B)Isavuconazole or posaconazole (C) |
| Fusarium spp. | Voriconazole or L-AmB (AII) | Voriconazole+L-AmB (AIII)Isavuconazole (C) |
| Scopulariopsis spp. | Voriconazole, L-AmB or isavuconazole (BII)** | |
| Phaeohyphomycosis (dematiaceous fungi) | Voriconazole or L-AmB (BIII), L-AmB+azole or echinocandin (BIII) | L-AmB (BIII)Isavuconazole (C) |
In all cases early surgical debridement, if possible, is strongly recommended. B: moderately recommended; C: marginally recommended; L-AmB: liposomal amphotericin B; AmB: amphotericin B.
Evidence supporting the use of antifungal combination therapy for mucormycosis is limited.4,9,38 Potential combinations include polyenes with azoles, or polyenes with echinocandins. In case of extensive disease, rapid progression, or poor general condition, guidelines suggest considering the addition of isavuconazole or posaconazole due to their favorable safety profiles and the absence of increased toxicity, despite the lack of proven benefit. ECIL-6 guidelines specifically mention the combination of posaconazole and amphotericin B with a BIII level of recommendation (Table 2), based on a short study that reported a 40% one-year survival rate with this treatment combination.28,38
In the salvage therapy scenario, isavuconazole and posaconazole have demonstrated efficacy in patients previously treated with L-AmB (AII).4,9,25,40 The VITAL trial included 11 patients treated with isavuconazole for refractory disease and 5 patients that due to intolerance to other treatments were treated with isavuconazole. The mortality rate at six weeks was 36% for those with refractory disease and 40% for those intolerants to other antifungals, comparable to the 39% mortality rate observed in the control group treated with L-AmB.25
Once response or stable disease is achieved, isavuconazole in its oral formulation, as well as posaconazole in the modified-released tablet form, is considered a reasonable option for step-down maintenance therapy.9
3.2IFI caused by other non-Aspergillus, non-Mucor molds or by rare emerging yeasts and dimorphic fungiFor scedosporiosis, voriconazole is strongly recommended as first-line treatment due to its superior outcomes compared with amphotericin B monotherapy (AII).4 Isavuconazole is noted as a potential future option since positive experience has been reported in a limited number of cases, but more information is considered to be required before it can be recommended as first-line therapy.8 For salvage therapy, voriconazole is recommended for Scedosporium spp. infections previously treated with amphotericin B. At this stage, no mention to isavuconazole is provided.
Invasive fungal disease caused by Lomentospora prolificans is recommended to be treated with a combination of voriconazole and terbinafine, with dosing guided by therapeutic drug monitoring (AII).4,18 Amphotericin B resulted in poorer outcomes than voriconazole monotherapy, therefore the recommendation is against its use. Similarly to Scedosporium invasive infections, success with isavuconazole has been reported with this azole in individual cases, but further evidence is still required.26
Fusariosis is treated with either voriconazole or amphotericin B, as there is insufficient data to recommend one over the other (AII).4,18 Given the variable minimum inhibitory concentrations of voriconazole exhibited by Fusarium species, combination therapy with both agents, followed by de-escalation to monotherapy, is considered the standard of care in some centers (BII). Isavuconazole has been used to treat fusariosis, but no solid evidence is available to make any recommendation.8
In Scopulariopsis invasive infections, isavuconazole is considered a first-line treatment, same as voriconazole.18 In phaeohyphomycosis, isavuconazole is marginally recommended. A summary of most of these management recommendations for non-Aspergillus molds invasive infections is provided in Table 2.
Regarding other microorganisms, in vitro activity of isavuconazole against Cryptococcus and other rare yeasts such as Trichosporon, Rhodotorula, Geotrichum, Saccharomyces and Pichia species is noted, but the evidence to consider its use is only enough for Trichosporon.6,7,36 However, reports describing reduced activity of isavuconazole compared to voriconazole and itraconazole are of concern.15
For endemic mycoses, case reports have described successful treatment of Blastomyces infections with isavuconazol, but L-AmB is considered the mainstay of management.37Sporothrix species have exhibited high in vitro minimum inhibitory concentrations to both voriconazole and isavuconazole,6 leading to a recommendation against their use.
Treatment of infections caused by species of the endemic dimorphic fungus Histoplasma continues to be based on guidelines for the use of itraconazole, although in severe infections or in profound immunosuppressed patients there is sufficient experience and the use of amphotericin B formulations is accepted.2,37 The use of voriconazole or posaconazole as initial or maintenance therapy has been scarce in histoplasmosis and the use of isavuconazole is even more anecdotal, so there are no agreed recommendations in this regard.16,35 A retrospective observational study on the use of isavuconazole in patients diagnosed with histoplasmosis has started recently in Spain (2024) to fill the lack of evidence in this endemic mycosis and to evaluate its potential usefulness and indication.
4Prophylaxis strategyFor anti-mold prophylaxis in high-risk hematologic patients, posaconazole (AI) and voriconazole (AII), remain the first-line agents, given the experience and positive outcomes from previous studies.13,29,39 No mention in clinical guidelines is made regarding the use of isavuconazole in this context. However, there is published experience on the use of isavuconazole in prophylaxis regimens different from those authorized by regulatory agencies, with contradictory and not always satisfactory results concerning breakthrough IFIs.3,11,20,30 Nonetheles, emergence of new anti-leukemia treatments (such as midostaurin, venetoclax, gilterinib, quizartinib, glasdegib, ivosidenib, etc.) has introduced challenges related to their potential drug–drug interactions and the risk of reduced efficacy when dose adjustments are made or when drug concentration, often unmeasurable or difficult to monitor, are affected. In this context, the use of isavuconazole in prophylaxis should be considered due to its lower potential in drug interactions via cytochrome P450 isoenzymes.1 However, further evaluations in this setting are needed.
Regarding prophylaxis in SOT patients, antifungal prophylaxis should be considered only for high-risk patients, such as lung transplant recipients, heart transplant recipients with acute graft rejection, cytomegalovirus disease or those who suffered a previous IA episode within the program in the previous two months. In lung transplant recipients, nebulized AmB (AII) is the drug of choice. For heart transplant recipients, itraconazole or caspofungin are preferred over voriconazole or posaconazole, although these recommendations appear to be based on the lack of experience with the newer triazole agents in this setting.13,19,39 In general, isavuconazole is not included as a suitable prophylactic option due the insufficient data. However, the latest guidelines suggest it could be considered an alternative and gather its increasingly use in clinical practice.10,19
5ConclusionIsavuconazole has emerged as a valuable antifungal therapy offering a safer profile, more predictable pharmacokinetics, and fewer drug interactions than other azoles. The increasing evidence available on its use has resulted in its incorporation into major clinical guidelines, particularly for the treatment of IA. Notably, the most recent consensus documents recommend isavuconazole at the same level as voriconazole. This trend reflects the fact that clinical guidelines recommendations often lag behind the reality of clinical practice. Furthermore, isavuconazole has shown promising results in mucormycosis and other rare fungal infections, though data in some areas remain limited. The lack of evidence in some circumstances highlights the importance of individualized treatment decisions guided by patient-specific factors and concomitant medications. Ongoing research and real-world experience are expected to further define isavuconazole's role across the spectrum of invasive fungal disease, including prophylaxis and treatment in diverse at-risk populations.
6FundingThe publication of this article has been funded by Pfizer. Pfizer has neither taken part, nor intervened in the content of this article.
7Conflicts of interestSdC declares no conflicts of interest. MS has participated in scientific consultancies and held conferences at meetings organised or under the sponsorship of Angelini, GSK, Gilead, Menarini, MSD, Pfizer and Shionogi.
