Isavuconazole Diffusion in Infected Human Brain

Rouzaud, Claire; Jullien, Vincent; Herbrecht, Anne; Palmier, B.; Lapusan, Simona; Morgand, Marjolaine; Guéry, Romain; Dureault, Amélie; Danion, François; Puget, Stéphanie; Goldwirt, Lauriane; Lanternier, Fanny; Lortholary, Olivier

doi:10.1128/aac.02474-18

Cited by 27 publications

(23 citation statements)

References 14 publications

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“…In patients with adverse events ISA plasma concentrations were always below 5.5 µg/mL. Recently, increased dosage up to 300 mg of ISA per day for treatment of cerebral invasive aspergillosis has been suggested based on two cases [ 25 ]. As ISA concentrations within the brain abscess and inflamed meninges were close to ISA plasma concentration but were much lower in normal brain tissue, we assume that ISA TDM might help to adequately dose and manage adverse events in central nervous system aspergillosis cases.…”

Section: Discussionmentioning

confidence: 99%

Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations

Zurl

Waller

Schwameis³

et al. 2020

JoF

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Isavuconazole (ISA) is a triazole antifungal agent recommended for treatment of invasive aspergillosis or mucormycosis. The objective of this study was to evaluate ISA levels in a real world setting in a mixed patient cohort including patients with non-malignant diseases and extracorporeal treatments, and to correlate findings with efficacy and safety outcomes. We investigated 33 ISA treatment courses in 32 adult patients with hematological and other underlying diseases and assessed the clinical response, side effects and ISA trough plasma concentrations. ISA treatment led to complete and partial response in 87% of patients and was well tolerated. The median ISA plasma concentration was 3.05 µg/mL (range 1.38–9.1, IQR 1.93–4.35) in patients without renal replacement therapy (RRT) or extracorporeal membrane oxygenation (ECMO) and significantly lower in patients with RRT including cases with additional ECMO or Cytosorb® adsorber therapy (0.88 µg/mL, range 0.57–2.44, IQR 0.71–1.21). After exclusion of values obtained from four patients with ECMO or Cytosorb® adsorber the median concentration was 0.91 µg/mL (range 0.75–2.44, IQR 0.90–1.36) in the RRT group. In addition to previous recommendations we propose to monitor ISA trough plasma concentrations in certain circumstances including RRT, other extracorporeal treatments and obesity.

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Section: Discussionmentioning

confidence: 99%

Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations

Zurl

Waller

Schwameis³

et al. 2020

JoF

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“…However, some providers may prefer adding a triazole with anti-Mucorales activity, such as posaconazole or isavuconazole, to initial treatment, as was done in Case 2 in this series [ 61 , 62 ]. Because of potentially better CNS penetration [ 63 ], isavuconazole is preferred to posaconazole by some clinicians, but both triazoles demonstrate good clinical outcomes in CNS infections [ 64–67 ]. Echinocandins show in vitro synergy with AmB against Rhizopus oryzae but display poor CNS penetration [ 68 ].…”

Section: Discussionmentioning

confidence: 99%

Isolated Cerebral Mucormycosis in Immunocompetent Adults who Inject Drugs: Case Reports and Systematic Review of the Literature

Meyerowitz

Sanchez

Mansour

et al. 2020

Open Forum Infectious Diseases

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Mucormycosis involves life-threatening rapidly progressive angioinvasion with infiltration across tissue planes, resulting in necrosis and thrombosis, most commonly seen in the setting of immunocompromised states. We describe two cases of isolated cerebral mucormycosis in immunocompetent adults and then describe this syndrome in detail in the context of systemic literature review. Using the criteria: 1) isolated cerebral disease; 2) mucormycosis (by PCR, culture or pathology); and 3) affected an immunocompetent individual, we identified 53 additional cases from 1969 to 2020. Of these 55 cases, approximately 60% occurred in men, >70% were in patients under age 35, 92% were associated with intravenous drug use, and >85% had infection centered in the basal ganglia. Many presented with cranial nerve deficits, headache, focal weakness, or altered mental status. No patient survived without amphotericin and steroid administration was associated with worse outcomes. Given the current opioid crisis, this syndrome may be seen more frequently.

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“…Although, there are some data of tissue penetration into tissue (e.g., brain and lungs), these data are mostly based on animal experiments [ 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Penetration of Isavuconazole in Ascites Fluid of Critically Ill Patients

Lahmer

Baires

Schmid

et al. 2021

JoF

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Fungal peritonitis is a life-threatening condition which is not only difficult to diagnose, but also to treat. Following recent guidelines, echinocandins and azoles are the recommended antimycotics for the management of intra-abdominal Candida spp. infections, with a favor for echinocandins in critically ill patients. However, the new extended spectrum triazole isavuconazole also has a broad spectrum against Candida spp. Data on its target-site penetration are sparse. Therefore, we assessed isavuconazole concentrations and penetration ratios in ascites fluid of critically ill patients. Obtaining of Isavuconazole plasma and ascites fluid levels as well penetration ratios using paracentesis in critically ill patients. Isavuconazole concentrations were quantified in human plasma and ascites by a liquid chromatography/tandem mass spectrometry (LC-MS/MS) method. Isavuconazole concentrations in plasma and ascites fluid were measured in sixteen critically ill patients. Isavuconazol levels in ascites fluid (1.06 µg/mL) were lower than plasma levels (3.08 µg/mL). Penetration ratio was 36%. In two out of sixteen patients, Candida spp., in detail C. glabrata and C. tropicalis, could be isolated. Cmax/MIC Ratio in plasma of 560 for C. glabrata and 2166 for C. tropicalis could be observed. Following our results, isavuconazole penetrates into ascites. Successful treatment in Candida spp. peritonitis depends on pathogen susceptibility.

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Isavuconazole Diffusion in Infected Human Brain

Cited by 27 publications

References 14 publications

Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations

Isavuconazole Treatment in a Mixed Patient Cohort with Invasive Fungal Infections: Outcome, Tolerability and Clinical Implications of Isavuconazole Plasma Concentrations

Isolated Cerebral Mucormycosis in Immunocompetent Adults who Inject Drugs: Case Reports and Systematic Review of the Literature

Penetration of Isavuconazole in Ascites Fluid of Critically Ill Patients

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