Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance

Ellsworth, Misti; Ostrosky-Zeichner, Luis

doi:10.3390/jof6040324

Cited by 83 publications

(64 citation statements)

References 48 publications

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“…It is also tolerated well for extended use, over six months. [ 43 44 ] Twenty-six percent of the patients received step-down treatment, 95% with posaconazole. These numbers are expected to rise with a longer follow up.…”

Section: Discussionmentioning

confidence: 99%

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India – Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1

Sen¹,

Honavar²,

Bansal³

et al. 2021

Indian Journal of Ophthalmology

320

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Purpose: COVID-19-associated rhino-orbital-cerebral mucormycosis (ROCM) has reached epidemic proportion during India’s second wave of COVID-19 pandemic, with several risk factors being implicated in its pathogenesis. This study aimed to determine the patient demographics, risk factors including comorbidities, and medications used to treat COVID-19, presenting symptoms and signs, and the outcome of management. Methods: This was a retrospective, observational study of patients with COVID-19-associated ROCM managed or co-managed by ophthalmologists in India from January 1, 2020 to May 26, 2021. Results: Of the 2826 patients, the states of Gujarat (22%) and Maharashtra (21%) reported the highest number of ROCM. The mean age of patients was 51.9 years with a male preponderance (71%). While 57% of the patients needed oxygen support for COVID-19 infection, 87% of the patients were treated with corticosteroids, (21% for > 10 days). Diabetes mellitus (DM) was present in 78% of all patients. Most of the cases showed onset of symptoms of ROCM between day 10 and day 15 from the diagnosis of COVID-19, 56% developed within 14 days after COVID-19 diagnosis, while 44% had delayed onset beyond 14 days. Orbit was involved in 72% of patients, with stage 3c forming the bulk (27%). Overall treatment included intravenous amphotericin B in 73%, functional endoscopic sinus surgery (FESS)/paranasal sinus (PNS) debridement in 56%, orbital exenteration in 15%, and both FESS/PNS debridement and orbital exenteration in 17%. Intraorbital injection of amphotericin B was administered in 22%. At final follow-up, mortality was 14%. Disease stage >3b had poorer prognosis. Paranasal sinus debridement and orbital exenteration reduced the mortality rate from 52% to 39% in patients with stage 4 disease with intracranial extension ( p < 0.05). Conclusion: Corticosteroids and DM are the most important predisposing factors in the development of COVID-19-associated ROCM. COVID-19 patients must be followed up beyond recovery. Awareness of red flag symptoms and signs, high index of clinical suspicion, prompt diagnosis, and early initiation of treatment with amphotericin B, aggressive surgical debridement of the PNS, and orbital exenteration, where indicated, are essential for successful outcome.

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Section: Discussionmentioning

confidence: 99%

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India – Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1

Sen¹,

Honavar²,

Bansal³

et al. 2021

Indian Journal of Ophthalmology

320

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“…Azole resistance mechanisms include overexpression of ABC transporters (ATP binding cassettes), mutation of the gene encoding the target enzyme (ERG11), ERG3 gene mutation which impairs azole-mediated cell membrane disruption [ 98 ]. Therefore, it is a reasonable treatment option for mucormycosis patients with other refractory disorders and posaconazole intolerance [ 99 ].…”

Section: Medical Management Of Mucormycosismentioning

confidence: 99%

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

et al. 2021

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Mucormycosis in patients who have COVID-19 or who are otherwise immunocompromised has become a global problem, causing significant morbidity and mortality. Infection is debilitating and fatal, leading to loss of organs and emotional trauma. Radiographic manifestations are not specific, but diagnosis can be made through microscopic examination of materials collected from necrotic lesions. Treatment requires multidisciplinary expertise, as the fungus enters through the eyes and nose and may even reach the brain. Use of the many antifungal drugs available is limited by considerations of resistance and toxicity, but nanoparticles can overcome such limitations by reducing toxicity and increasing bioavailability. The lipid formulation of amphotericin-B (liposomal Am-B) is the first-line treatment for mucormycosis in COVID-19 patients, but its high cost and low availability have prompted a shift toward surgery, so that surgical debridement to remove all necrotic lesions remains the hallmark of effective treatment of mucormycosis in COVID-19. This review highlights the pathogenesis, clinical manifestation, and management of mucormycosis in patients who have COVID-19.

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“…Except for these three echinocandins, all isolates were susceptible to fluconazole (MIC, 0.25 mg/L), itraconazole (MIC, 0.06 mg/L), voriconazole (MIC, <0.008 mg/L), 5-fluorocytosine (MIC, <0.06 mg/L) and, according to the epidemiological cutoff values established by the CLSI [ 13 ], they also expressed wild-type susceptibility to amphotericin B (MIC, 0.5 mg/L) and posaconazole (MIC, 0.03 mg/L). The effectiveness of isavuconazole against all major Candida species has been evaluated [ 14 ]. According to these reports, the susceptibility test for isavuconazole was performed using the MIC strip method (Liofilchem, Roseto degli Abruzzi, TE, Italy) [ 15 , 16 ] and showed an MIC of 0.5 mg/L.…”

Section: Case Report and Resultsmentioning

confidence: 99%

Resistance to Echinocandins Complicates a Case of Candida albicans Bloodstream Infection: A Case Report

Trovato

Bongiorno

Calvo

et al. 2021

JoF

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Invasive candidiasis is known to be one of the most common healthcare-associated complications and is caused by several Candida species. First-line drugs, particularly echinocandins, are effective, but there are increasing reports of resistance to these molecules, though rarely related to C. albicans. Even though the rate of echinocandins resistance remains low (<3%), sporadic cases are emerging. Here, we present a case of bloodstream infection by a pan-echinocandin-resistant Candida albicans affecting a critically ill patient, who died in an intensive care unit following therapeutic failure and multiple organ dysfunction syndrome. This case highlights the need to suspect pan-echinocandin resistance in patients with prolonged echinocandin exposure, particularly in the presence of urinary tract colonization. Our study shows the importance of sequencing to predict therapeutic failure in patients treated with echinocandins and persistent candidemia.

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Isavuconazole: Mechanism of Action, Clinical Efficacy, and Resistance

Cited by 83 publications

References 48 publications

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India – Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1

Epidemiology, clinical profile, management, and outcome of COVID-19-associated rhino-orbital-cerebral mucormycosis in 2826 patients in India – Collaborative OPAI-IJO Study on Mucormycosis in COVID-19 (COSMIC), Report 1

Mucormycosis in Indian COVID-19 Patients: Insight into Its Patho-Genesis, Clinical Manifestation, and Management Strategies

Resistance to Echinocandins Complicates a Case of Candida albicans Bloodstream Infection: A Case Report

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