Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis

Manesh, Abi; Devasagayam, Emily; Bhanuprasad, Kundakarla; Mathew, Sumith K; Karthik, Rajiv; Mathew, Binu; Varghese, George

doi:10.1128/aac.01085-22

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…Posaconazole treatment of CAM has been associated with decreased in-hospital mortality [11 ▪ ]. Manesh et al [74] found that crushing delayed-release posaconazole tablets was associated with good plasma concentrations and outcomes in 19 patients with rhino-orbito-cerebral MCR [74].…”

Section: Treatment Of Mucormycosismentioning

confidence: 99%

Mucormycosis: update on clinical presentation, diagnosis, and treatment

Dailey Garnes,

Kontoyiannis

2023

Current Opinion in Infectious Diseases

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Purpose of review Mucormycosis (MCR) is a common opportunistic mold infection, and Mucorales were recently designated by WHO as priority pathogens. The interest in this infection has risen significantly since the major outbreak of MCR in the context of the COVID-19 pandemic, particularly in India. Herein, we summarize recently (last 24 months) published information regarding clinical aspects of MCR. Recent findings The disease remains protean in its clinical presentation, difficult to diagnose, and challenging to treat. In 2021, cases of COVID-19-associated mucormycosis (CAM) exploded in India during COVID-19 and manifested primarily as sino-orbital or sino-cerebral disease. Its classic risk factors included the triad of COVID-19, uncontrolled diabetes mellitus and use of corticosteroids. Despite difficulties in the timely diagnosis of MCR, significant progress has been made with the use of molecular techniques in blood to assist with earlier diagnosis, which can facilitate earlier appropriate therapy and improve outcomes. In addition, advances have been made in the use of imaging to stage the disease, determining what types of multimodal therapy are required depending on staging, and tissue-based identification of Mucorales. Summary Although the outlook for MCR has improved, effective new antifungals, risk stratification, and the optimal multimodality approaches remain an unmet need.

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Section: Treatment Of Mucormycosismentioning

confidence: 99%

Mucormycosis: update on clinical presentation, diagnosis, and treatment

Dailey Garnes,

Kontoyiannis

2023

Current Opinion in Infectious Diseases

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“…95,108 Therapeutic target attainment can be particularly challenging for the pediatric population, with a number of strategies reported to optimize therapy, including crushing delayed release tablets. [109][110][111][112][113] A dose-response relationship between posaconazole and most toxicities has not been found. 114 The exception is dosedependent pseudohyperaldosteronism, which manifests mainly in hypokalemia and hypertension.…”

Section: Posaconazolementioning

confidence: 99%

“…However, these targets remain controversial; 105–107 animal data suggest that substantially higher concentrations may be needed for optimal treatment of mold infections 95,108 . Therapeutic target attainment can be particularly challenging for the pediatric population, with a number of strategies reported to optimize therapy, including crushing delayed release tablets 109–113 . A dose‐response relationship between posaconazole and most toxicities has not been found 114 .…”

Section: Antifungalsmentioning

confidence: 99%

Antimicrobials in patients with hematologic malignancies and recipients of hematopoietic cell transplantation and other cellular therapies

Tverdek,

Escobar,

Liu

et al. 2023

Transplant Infectious Dis

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BackgroundAppropriate use of antimicrobials for hematologic malignancy, hematopoietic stem cell transplant recipients, and other cellular therapies is vital, with infection causing significant morbidity and mortality in this unique population of immunocompromised hosts. However, often in this population the choice and management of antimicrobial therapy is complex. When selecting an antimicrobial agent, key considerations include the need for dose adjustments due to renal or hepatic impairment, managing drug interactions, the potential for additive drug toxicity among those receiving polypharmacy and therapeutic drug monitoring. Other factors include leveraging pharmacodynamic principles to enable optimization of directed therapy against challenging pathogens, as well as judicious use of antimicrobials to limit drug resistance and adverse drug reactions.SummaryThis review summarizes the clinical considerations for commonly used antimicrobials in this setting, including antibacterial, antiviral, and antifungal agents. image

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“…4,5 Given the difficulty achieving therapeutic C min with POS-S, especially in patients with enteral feeding tubes, poor nutritional intake, or critical illness, we welcomed the reported success of crushing POS delayed-release tablets (POS-DRT) for either enteral feeding tube or oral administration in adults. [6][7][8] Similar data in children are lacking.…”

Section: Introductionmentioning

confidence: 99%

Successful enteral administration of crushed posaconazole delayed‐release tablets in children

Bio,

Hiroshima,

Schwenk

et al. 2023

Pediatric Blood & Cancer

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Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed‐release tablets (POS‐DRT) show promise in adults; limited evidence exists in children. We used crushed POS‐DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS‐DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment.

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Efficacy of Crushed Delayed-Release Posaconazole Tablets in Rhino-Orbito-Cerebral Mucormycosis

Cited by 10 publications

References 14 publications

Mucormycosis: update on clinical presentation, diagnosis, and treatment

Mucormycosis: update on clinical presentation, diagnosis, and treatment

Antimicrobials in patients with hematologic malignancies and recipients of hematopoietic cell transplantation and other cellular therapies

Successful enteral administration of crushed posaconazole delayed‐release tablets in children

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