Successful treatment of <i>Aspergillus fumigatus</i> sternal osteomyelitis with isavuconazole in a heart transplant recipient

Assaf, Ady; Faure, Emmanuel; Sermet, Kevin; Loridant, Séverine; Leroy, Jordan; Goéminne, Céline; Dozier, Aurelie; Chopin, Marie‐Charlotte; Panaget, Sophie; Faure, Karine; Vuotto, Fanny

doi:10.1111/tid.13313

Cited by 11 publications

(6 citation statements)

References 20 publications

(35 reference statements)

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“…A total of 63 patients (46 males; 73%), with a mean age of 37.9 years [standard deviation (SD) = 25.3], suffering osteomyelitis due to Aspergillus spp. were identified during the study period [ 1 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 ].…”

Section: Resultsmentioning

confidence: 99%

Osseous Infections Caused by Aspergillus Species

et al. 2022

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Background: Osteomyelitis caused by Aspergillus spp. is a severe, but rare, clinical entity. However, clear guidelines regarding the most effective medical management have not yet been established. The present study is a literature review of all such cases, in an effort to elucidate epidemiology, as well as the therapeutic management and the infection’s outcome. Methods: A thorough review of all reports of osteomyelitis of the appendicular and the axial skeleton, without the skull and the spine, caused by Aspergillus spp. was undertaken. Data about demographics, imaging techniques facilitating diagnosis, causative Aspergillus, method of mold isolation, antifungal treatment (AFT), surgical treatment, as well as the infection’s outcome were recorded and evaluated. Results: A total of 63 cases of osseous infection due to Aspergillus spp. were identified. The studied population’s mean age was 37.9 years. The most commonly affected site was the rib cage (36.8%). Most hosts suffered immunosuppressive conditions (76.2%). Regarding imaging methods indicating diagnosis, computer tomography (CT) was performed in most cases (42.9%), followed by plain X-ray (41.3%) and magnetic resonance imaging (MRI) (34.9%). The most frequent isolated mold was Aspergillus fumigatus (49.2%). Cultures and/or histopathology were used for definite diagnosis in all cases, while galactomannan antigen test was additionally used in seven cases (11.1%), polymerase chain reaction (PCR) in four cases (6.3%), and beta-d-glucan testing in three cases (4.8%). Regarding AFT, the preferred antifungal was voriconazole (61.9%). Most patients underwent surgical debridement (63.5%). The outcome was successful in 77.5%. Discussion: Osteomyelitis due to Aspergillus spp. represents a severe infection. The available data suggest that prolonged AFT in combination with surgical debridement is the preferred management of this infection, while identification of the responsible mold is of paramount importance.

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Section: Resultsmentioning

confidence: 99%

Osseous Infections Caused by Aspergillus Species

et al. 2022

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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%

“…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%

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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“…The child had no obvious adverse effects, and the brain infection foci shrank. Similarly, Assaf et al (2020) reported a patient with invasive Aspergillus fumigatosis and sternal osteomyelitis after heart transplantation who discontinued VOR due to severe cutaneous and neurotoxicity and subsequently improved after switching to ISA monotherapy. Therefore, patients intolerant or resistant to other triazole antifungal drugs should also consider switching to ISA therapy.…”

Section: Clinical Efficacy Iamentioning

confidence: 91%

Clinical research advances of isavuconazole in the treatment of invasive fungal diseases

Zhang

Shen

Feng

2022

Front. Cell. Infect. Microbiol.

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PurposeInvasive fungal diseases (IFD) are a major global public health concern. The incidence of IFD has increased the demand for antifungal agents. Isavuconazole (ISA) is a new triazole antifungal agent that has shown promising efficacy in the prophylaxis and treatment of invasive fungal diseases. The aim of this review is to summarize the recent real-world experiences of using ISA for the treatment and prevention of IFD.MethodsWe performed a comprehensive literature search of the MEDLINE, PubMed, Embase, and Cochrane databases for clinical applications of ISA in the real world. Tables and reference lists are presented for this systematic review.ResultsIFD poses a major threat to public health and causes high mortality rates. ISA may provide a good treatment. For example, the efficacy of ISA in the treatment of invasive aspergillosis (IA) is comparable to that of voriconazole, and its efficacy in the treatment of invasive mucormycosis (IM) is similar to that of liposomal amphotericin B (L-AmB); therefore, ISA is recommended as the first-line treatment for IA and IM. ISA can also achieve good efficacy in the treatment of invasive candidiasis (IC) and can be used as an alternative to de-escalation therapy after first-line drug therapy. In addition, most studies have shown the efficacy and safety of ISA for the prophylaxis of IFD.ConclusionTaken together, ISA are expected to become a new choice for the treatment and prevention of IFD because of their good tolerability, high bioavailability, and few drug interactions.

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Successful treatment of Aspergillus fumigatus sternal osteomyelitis with isavuconazole in a heart transplant recipient

Cited by 11 publications

References 20 publications

Osseous Infections Caused by Aspergillus Species

Osseous Infections Caused by Aspergillus Species

Antifungal Drugs TDM: Trends and Update

Clinical research advances of isavuconazole in the treatment of invasive fungal diseases

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