Cerebral Rhizomucor Infection Treated by Posaconazole Delayed-Release Tablets in an Allogeneic Stem Cell Transplant Recipient

Andrey, Diego O.; Kaiser, Laurent; Emonet, Stéphane; Erard, Véronique; Chalandon, Yves; Delden, Christian van

doi:10.1016/j.ijid.2016.12.014

Cited by 12 publications

(7 citation statements)

References 17 publications

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“…70 Rapid and aggressive treatment with combined surgical debridement/resection and medical therapy is essential for a successful outcome from ROCM. 46,94,101,151,157,162,[165][166][167] High-dose LFAB should be given concurrently. 168,169 Amphotericin B 110,170 and ISAV 171,172 are Food and Drug Administration (FDA)-approved agents for the treatment of mucormycosis, while POSA has been used off-label as salvage or step-down therapy.…”

Section: Rhino-orbital-cerebral Mucormycosismentioning

confidence: 99%

Mucormycosis

Reid

Lynch

Fishbein

et al. 2020

Semin Respir Crit Care Med

151

108

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Mucormycosis is an infection caused by a group of filamentous molds within the order Mucorales. Infections may result from ingestion of contaminated food, inhalation of spores into the nares or lungs, or inoculation into disrupted skin or wounds. In developed countries, mucormycosis occurs primarily in severely immunocompromised hosts (e.g., those with hematological malignancies, organ transplantation, neutropenia, autoimmune disorders, or other impairments in immunity). Only 6 to 10% of cases occur in subjects with no underlying disease. In contrast, in developing countries, most cases of mucormycosis occur in persons with poorly controlled diabetes mellitus or in immunocompetent subjects following trauma. Mucormycosis exhibits a marked propensity to invade blood vessels, leading to thrombosis, necrosis, and infarction of tissue. Mortality associated with invasive mucormycosis is high (> 30–50%), with 90% mortality associated with disseminated disease. Mortality rates are much lower, though still significant (10–30%), among patients with localized cutaneous disease.The diagnosis of mucormycosis relies upon histopathology and culture. Blood tests are of limited diagnostic value. Even with disseminated disease, blood cultures are usually negative. Mucorales have a distinct histological appearance, with irregular, nonseptate hyphae that branch at right angles. Cultures and/or polymerase chain reaction (PCR) are important to identify the genera.Based on anatomic localization, mucormycosis can be classified as one of six forms: (1) rhino-orbital-cerebral mucormycosis (ROCM), (2) pulmonary, (3) cutaneous, (4) gastrointestinal (GI), (5) disseminated, and (6) mucormycosis of uncommon sites. Among diabetics, ROCM is the most common clinical presentation, whereas lung involvement is uncommon. In contrast, among organ transplant recipients or patients with hematological malignancies (HemeM), pulmonary and disseminated diseases are most common. Mucormycosis can progress rapidly, and delay in initiation of treatment by even a few days markedly worsens outcomes.Due to the rarity of mucormycosis, randomized controlled therapeutic trials have not been performed. Lipid formulations of amphotericin B (LFAB) are the mainstay of therapy, but the newer triazoles, posaconazole (POSA) and isavuconazole (ISAV) (the active component of the prodrug isavuconazonium sulfate), may be effective in patients refractory to or intolerant of LFAB. Early surgical debridement or excision plays an important adjunctive role. Additional studies are required to assess the optimal duration of therapy as well as the specific roles of LFAB and the triazoles in the treatment of mucormycosis.

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Section: Rhino-orbital-cerebral Mucormycosismentioning

confidence: 99%

Mucormycosis

Reid

Lynch

Fishbein

et al. 2020

Semin Respir Crit Care Med

151

108

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“…127 Rapid and aggressive treatment with combined surgical debridement/resection and medical therapy is essential for successful outcome of ROCM. 147,184,[187][188][189] High-dose lipid formulation of AmB (LFAB) should be given concurrently. 190,191 POSA is considered salvage therapy, but complete responses were achieved with POSA in 8 of 12 cases in a recent series of ROCM.…”

Section: Rhino-orbital-cerebral Involvementmentioning

confidence: 99%

Fungal Infections Complicating Lung Transplantation

Clark

Weigt

Fishbein³

et al. 2018

Semin Respir Crit Care Med

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Lung transplantation is an increasingly utilized modality for treating advanced lung disease. However, lung transplant recipients (LTRs) experience high rates of infection-related mortality and, compared with other solid organ transplant recipients, are at increased risk of infectious complications given the intensity of immunosuppression employed, the presence of airway abnormalities after surgery and exposure of the allograft to the environment. Fungal infections, particularly mold infections, are problematic after transplantation as they are often associated with limited treatment options and poor outcomes. We describe the non- fungal infections occurring in LTRs, including their epidemiology, clinical features, and treatment.

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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%

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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Cerebral Rhizomucor Infection Treated by Posaconazole Delayed-Release Tablets in an Allogeneic Stem Cell Transplant Recipient

Cited by 12 publications

References 17 publications

Mucormycosis

Mucormycosis

Fungal Infections Complicating Lung Transplantation

Antifungal Drugs TDM: Trends and Update

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