Successful treatment with isavuconazole of subcutaneous phaeohyphomycosis in a kidney transplant recipient

Gasperina, Daniela Dalla; Lombardi, Doménico; Rovelli, Cristina; Rosa, Zaira Di; Lepera, Valentina; Baj, Andreina; Nava, Alice; Lombardi, Giuseppe; Grossi, Paolo

doi:10.1111/tid.13197

Cited by 11 publications

(6 citation statements)

References 19 publications

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“…21 Other advantages lie in its lower potential for drug–drug interactions and the lack of sulfobutyl-ether β-cyclodextrin. 15 Nevertheless, the available experience for the treatment of IMD in SOT recipients is scarce and restricted to case reports 22 and PK studies. 23,24 The only cohort study reported to date was performed in a single center where lung transplant (LuT) recipients with Aspergillus tracheobronchitis were overrepresented.…”

Section: Introductionmentioning

confidence: 99%

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice

et al. 2022

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Background. Isavuconazole has theoretical advantages over other mold-active triazoles for the treatment of invasive aspergillosis and mucormycosis after solid organ transplantation (SOT). The available clinical experience, nevertheless, is scarce. Methods. We performed a retrospective study including all adult SOT recipients with proven or probable invasive mold disease (IMD) that received isavuconazole for ≥24 h as first-line or salvage therapy at 10 Spanish centers between September 2017 and November 2021. The primary efficacy outcome was clinical response (complete or partial resolution of attributable symptoms and findings) by weeks 6 and 12. Safety outcomes included the rates of treatment-emergent adverse events and premature isavuconazole discontinuation. Results. We included 81 SOT recipients that received isavuconazole for a median of 58.0 days because of invasive aspergillosis (n = 71) or mucormycosis (n = 10). Isavuconazole was used as first-line (72.8%) or salvage therapy due because of previous treatment-emergent toxicity (11.1%) or refractory IMD (7.4%). Combination therapy was common (37.0%), mainly with an echinocandin or liposomal amphotericin B. Clinical response by weeks 6 and 12 was achieved in 53.1% and 54.3% of patients, respectively, and was more likely when isavuconazole was administered as first-line single-agent therapy. At least 1 treatment-emergent adverse event occurred in 17.3% of patients, and 6.2% required premature discontinuation. Daily tacrolimus dose was reduced in two-thirds of patients by a median of 50.0%, although tacrolimus levels remained stable throughout the first month of therapy. Conclusions. Isavuconazole is a safe therapeutic option for IMD in SOT recipients, with efficacy comparable to other patient groups.

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Section: Introductionmentioning

confidence: 99%

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice

et al. 2022

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“…As a result, we reviewed 228 published reports. We identified and included 149 reports on 201 cases of dematiaceous fungal infections in SOT recipients 21–169 . The majority (134/149; 90%) of included reports scored ≥ 2 of three possible points on our bias assessment (Table S4).…”

Section: Resultsmentioning

confidence: 99%

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta‐analysis

Radcliffe

Azar

et al. 2022

Transplant Infectious Dis

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Background: Dematiaceous fungi cause a number of infectious syndromes referred to as phaeohyphomycosis among both immunocompetent and immunocompromised hosts. We performed a systematic review to characterize these infections in solid organ transplant recipients (SOTR). Methods:We searched PubMed database (last searched 1/6/2022) for Englishlanguage reports on dematiaceous fungal infections in SOTR. Included reports needed individualized demographic, treatment, and outcome data; pediatric reports were excluded. A universally applicable bias assessment was performed on reports. Models for infection type and outcome were created using the Bayesian paradigm. Results:We included 149 reports on 201 cases of dematiaceous fungal infections in SOTR. The mean age was 54 years, 72% were men, and kidney recipients accounted for 61% of cases. Skin and soft tissue infection (SSTI) was the most common infectious syndrome (73%). Death from infection occurred in 7% of cases (14/201), with disseminated (32%) cases having the highest mortality. Our model for infection type predicted the relative probability of central nervous system infection to be highest in liver recipients. Across all transplant types, higher relative probabilities of disseminated and pulmonary infections occur in the early post-transplant period, and the predicted probabilities for these infection types decreased after 100 months post-transplantation.Discussion: We identified SSTI as the most common dematiaceous fungal infections in SOTR. Disseminated infections carried the worst prognosis. The evidence in this review is limited by the heterogeneity of included cases. No funding source was used, and this review's protocol was not registered.

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“…However, PSZ tablets, which are widely used and unlikely to result in underexposure, may not justify routine TDM. 168,169,234,235,236,[238][239][240][241][244][245][246] Blood Trough 261,262,268,[281][282][283][284]314,315,320,323,327,330,331,333,340 Concentrations Targets 341,344,347,350,352,353,355,[358][359][360][361] and TDM Indications 364,522,[526][527][528][529][530][531][532][533][534][535][536]…”

Section: Discussionmentioning

confidence: 99%

“…2.2 (tablet) 533,534 2.5 234,245,366,[530][531][532]540,542 25-50 534,539 4-5 537 Documented exposure in CNS infection 2-5.8 69,535,536 3.6 236,[238][239][240][241]536 Concentration target ranges are, indicative; multidisciplinary approaches facilitate the real-life personalization of management, addressing one clinical condition in one patient at a given time. TDM access is of growing recognized interest, depending on disease severity, but cost and availability limit its use worldwide.…”

Section: Discussionmentioning

confidence: 99%

“…AF TDM cases in real-life settings (pathogens, underlying diseases, 69,71–73,75,81 trends per year, 84,234,235,236,238,239,241,244,245,344–348 CNS 532–539 localization 541–566 ) 364,370,499,522,527–530 Trends are concerning a majority of mucomycosis and aspergillosis, in oncohematology and transplantation. VRZ, more recently PSZ tablets and ISZ are the most represented.…”

Section: Tdm For Af Drugsmentioning

confidence: 99%

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Antifungal Drugs TDM: Trends and Update

Kably

Launay

Derobertmasure

et al. 2022

Therapeutic Drug Monitoring

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The increasing burden of invasive fungal infections results in growing challenges to antifungal (AF) therapeutic drug monitoring (TDM). This review aims to provide an overview of recent advances in AF TDM. Methods:We conducted a PubMed search for articles during 2016-2020 using "TDM" or "pharmacokinetics" or "drug-druginteraction" with "antifungal," consolidated for each AF. Selection was limited to English language articles with human data on drug exposure.Results: More than 1000 articles matched the search terms. We selected 566 publications. The latest findings tend to confirm previous observations in real-life clinical settings. The pharmacokinetic variability related to special populations is not specific but must be considered. AF benefit-to-risk ratio, drug-drug interaction (DDI) profiles, and minimal inhibitory concentrations for pathogens must be known to manage at-risk situations and patients. Itraconazole has replaced ketoconazole in healthy volunteers DDI studies. Physiologically based pharmacokinetic modeling is widely used to assess metabolic azole DDI. AF prophylactic use was studied more for Aspergillus spp. and Mucorales in oncohematology and solid organ transplantation than for Candida (already studied). Emergence of central nervous system infection and severe infections in immunocompetent individuals both merit special attention. TDM is more challenging for azoles than amphotericin B and echinocandins. Fewer TDM requirements exist for fluconazole and isavuconazole (ISZ); however, ISZ is frequently used in clinical situations in which TDM is recommended. Voriconazole remains the most challenging of the AF, with toxicity limiting high-dose treatments. Moreover, alternative treatments (posaconazole tablets, ISZ) are now available.Conclusions: TDM seems to be crucial for curative and/or longterm maintenance treatment in highly variable patients. TDM poses fewer cost issues than the drugs themselves or subsequent treatment issues. The integration of clinical pharmacology into multidisciplinary management is now increasingly seen as a part of patient care.

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Successful treatment with isavuconazole of subcutaneous phaeohyphomycosis in a kidney transplant recipient

Cited by 11 publications

References 19 publications

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice

Isavuconazole for the Treatment of Invasive Mold Disease in Solid Organ Transplant Recipients: A Multicenter Study on Efficacy and Safety in Real-life Clinical Practice

Dematiaceous fungal infections in solid organ transplantation: Systematic review and Bayesian meta‐analysis

Antifungal Drugs TDM: Trends and Update

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