Isavuconazole in the Treatment of Coccidioidal Meningitis

Heidari, Arash; Quinlan, Miriam; Benjamin, D. Paul; Laurence, Brett; Mu, Anandit; Ngai, Tiffany; Hoffman, Wes J.; Cohen, Stuart H.; Mchardy, Ian Howard; Johnson, Royce H.; Thompson, George R.

doi:10.1128/aac.02232-18

Cited by 29 publications

(15 citation statements)

References 22 publications

(14 reference statements)

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“…If there is treatment failure, a serum fluconazole trough should be checked for therapeutic levels. Other azole options to treat active pulmonary coccidioidomycosis include itraconazole, voriconazole, posaconazole, or isavuconazole [ 36 , 37 ]. Notably, echinocandins have minimal activity against Coccidioides and should not be used as monotherapy for coccidioidomycosis.…”

Section: Discussionmentioning

confidence: 99%

Coccidioidomycosis in Allogeneic Stem Cell Transplant Recipients: Case Series and Review of the Literature

Saling

Gea‐Banacloche

Trickett

et al. 2021

JoF

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Coccidioides is an endemic fungus of the Southwest United States that causes the disease coccidioidomycosis. Immunocompromised persons are at increased risk for severe infection and dissemination. One such population is allogeneic bone marrow transplant (allo-HCT) recipients, but accounts of coccidioidal infection in these patients have rarely been documented. We present two cases of Coccidioides in allo-HCT recipients with good outcomes: one patient who developed pulmonary coccidioidomycosis in the late post-engraftment phase and another with known controlled disseminated infection at the time of transplant. A review of the literature identified 19 allo-HCT recipients with coccidioidomycosis. Due to the limited published literature, no guidelines have yet been established regarding optimal prophylaxis and treatment of Coccidioides infection in allo-HCT recipients. Candidates for transplantation should undergo a rigorous pre-transplant assessment to identify evidence of prior or active coccidioidomycosis. In our experience, patients who visit or live in Coccidioides-endemic areas should receive primary prophylaxis for at least the first 100 days post-transplant, and duration should be extended as long as the patient remains on immunosuppression. Those with prior infection should receive secondary prophylaxis while immunosuppressed. Patients with active infection should have treatment and stabilization of infection and continue anti-fungal treatment through immunosuppression.

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Section: Discussionmentioning

confidence: 99%

Coccidioidomycosis in Allogeneic Stem Cell Transplant Recipients: Case Series and Review of the Literature

Saling

Gea‐Banacloche

Trickett

et al. 2021

JoF

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“…Isavuconazole (ISAV), the active moiety of the triazole antifungal prodrug isavuconazonium sulfate (ISAVUSULF), has demonstrated potent in vitro activity against isolates of Coccidioides spp. Clinical studies in small cohorts of patients have reported good clinical outcomes with this triazole ( 6 , 7 ). Experimental models with Coccidioides spp.…”

Section: Textmentioning

confidence: 99%

Efficacy and Associated Drug Exposures of Isavuconazole and Fluconazole in an Experimental Model of Coccidioidomycosis

Kovanda

Sass

Martinez

et al. 2021

Antimicrob Agents Chemother

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Coccidioides spp. are important pathogens in endemic regions and new treatment options are needed. Isavuconazonium sulfate (ISAVUSULF) and fluconazole (FLU) were evaluated in experimental disseminated coccidioidomycosis to characterize drug exposures associated with efficacy. Macrobroth dilution was performed on Coccidioides isolates to measure minimal effective concentrations (MEC) and minimal fungicidal concentrations (MFC). Mice were inoculated with Coccidioides posadasii (Silveira strain). Treatment started 4 days post-inoculation. (Model 1) Mice were treated 19 days plus 30-day off-therapy observation, measuring survival through day 49 and residual fungal burden. Treatments included ISAVUSULF (prodrug: 186, 279, or 372 mg/kg twice-daily), FLU (20 or 100 mg/kg once-daily), and untreated. Model 2 included 7-day treatment with ISAVUSULF (prodrug: 74.4, 111.6, or 148.8 mg/kg twice-daily), FLU (20 or 100 mg/kg once-daily), and untreated. Serial plasma and tissues samples were obtained for PK and fungal burden measurement, respectively. MEC50 were 0.39 mg/L (ISAV) and 12.5 mg/L (FLU). Treatment with ISAVUSULF186 or both FLU doses resulted in higher survival compared to untreated. Treatment with ISAVUSULF 186 or 279 mg/kg twice-daily or FLU 100 mg/kg reduced fungal burden in all organs (Model 1). In model 2, >1 log10 CFU/organ reduction was demonstrated, with ISAV AUCs achieved with 111.6 mg/kg twice-daily (56.8 mg•h/L), in the spleen and liver. FLU AUCs, 100 and 500 mg•h/L, for 20 and 100 mg/kg doses, respectively, resulted in >1 log10 CFU/organ mean reduction in all organs. ISAVUSULF and FLU improved survival and reduced fungal burden. Increasing plasma drug exposures resulted in decreases in fungal burden.

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“…After exclusion of reports published in non-English language or in which clinical and therapeutic data were not available for the purpose of the present review, a total of 41 cases have been included. Clinical and demographic characteristics, details of the antifungal treatment, outcome and adverse effects reported on these patients are summarized in Table 2 [ 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Thirty-three out of 42 (78.5%) patients were male and the mean age was 52 years (range 20–79).…”

Section: Isavuconazole In Non-hematological Patientsmentioning

confidence: 99%