Safety, Tolerance, and Efficacy of Posaconazole Therapy in Patients with Nonmeningeal Disseminated or Chronic Pulmonary Coccidioidomycosis

Catanzaro, Antonino; Cloud, Gretchen A.; Stevens, David A.; Levine, Bernard E.; Williams, Pamela R. D.; Johnson, Royce H.; Rendón, Adrián; Mirels, Laurence F.; Lutz, Jon E.; Holloway, Melissa; Galgiani, John N.

doi:10.1086/519937

Cited by 111 publications

(59 citation statements)

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“…Absorption appears to be adequate in most cases, and serum concentrations were fairly consistent during treatment of coccidioidomycosis with doses of 400 to 800 mg once daily (201). However, there have been cases reported where adequate serum concentrations were difficult to achieve in patients with prolonged neutropenia or with graft-versus-host disease.…”

Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 95%

“…Seven of the patients in that study had disease limited to the lungs, and the other eight had disseminated nonmeningeal infections. Posaconazole dosing was described as 800 mg/day in divided doses; however, the report was not clear on whether this meant 400 mg every 12 h or 200 mg every 6 h. A similar open-label study was reported for patients without failed prior therapy (201). Patients with chronic pulmonary or nonmeningeal disseminated coccidioidomycosis were treated with 400 mg of posaconazole once daily or 800 mg once daily (two patients) for a median of 173 days.…”

Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 99%

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Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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SUMMARY Coccidioidomycosis is the endemic mycosis caused by the fungal pathogens Coccidioides immitis and C. posadasii . This review is a summary of the recent advances that have been made in the understanding of this pathogen, including its mycology, genetics, and niche in the environment. Updates on the epidemiology of the organism emphasize that it is a continuing, significant problem in areas of endemicity. For a variety of reasons, the number of reported coccidioidal infections has increased dramatically over the past decade. While continual improvements in the fields of organ transplantation and management of autoimmune disorders and patients with HIV have led to dilemmas with concurrent infection with coccidioidomycosis, they have also led to advances in the understanding of the human immune response to infection. There have been some advances in therapeutics with the increased use of newer azoles. Lastly, there is an overview of the ongoing search for a preventative vaccine.

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Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 95%

Section: Advances In Antifungal Therapy For Coccidioidomycosismentioning

confidence: 99%

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

et al. 2013

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“…Bronchoscopy and bronchoalveolar lavage (BAL) were performed at the University of California, San Francisco, Medical Center at approximately 3,5,8,12, or 24 h after the last POS dose. The exact time that the lavage was performed was recorded.…”

Section: Methodsmentioning

confidence: 99%

“…Participation was voluntary, and written informed consent was obtained from each subject. The enrolled subjects were divided into five groups of four subjects each, with bronchoscopy times at approximately 3,5,8,12, and 24 h after the final dose. The subjects were scheduled to receive a bronchoscopy as part of normal posttransplantation care; their POS dose times were planned so that the elapsed time between the last dose and bronchoscopy corresponded to their time group assignment.…”

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Steady-State Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole in Lung Transplant Recipients

Conte

DeVoe²,

Little

et al. 2010

Antimicrob Agents Chemother

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This prospective study evaluated the plasma and intrapulmonary pharmacokinetics and pharmacodynamics (PKPD) of posaconazole (POS) in lung transplant recipients. Twenty adult lung transplant patients were instructed to take a 400-mg POS oral suspension twice daily (BID) with a high-fat meal for a total of 14 doses. Pulmonary epithelial lining fluid (ELF) and alveolar cell (AC) samples were obtained via bronchoalveolar lavage, and blood samples were collected at the approximate time of bronchoscopy. POS concentrations were assayed using liquid chromatography with tandem mass spectrometry. The maximum concentrations (C max ) (mean ؎ standard deviation [SD]) in plasma, ELF, and AC were 1.3 ؎ 0.4, 1.3 ؎ 1.7, and 55.4 ؎ 44.0 g/ml. POS concentrations in plasma, ELF, and AC did not decrease significantly, indicating slow elimination after multiple dosing. Mean concentrations of POS in plasma, ELF, and AC were above the MIC 90 (0.5 g/ml) for Aspergillus species over the 12-h dosing interval and for 24 h following the last dose. Area under the concentration-time curve from 0 to 12 h (AUC 0-12 )/MIC 90 ratios in plasma, ELF, and AC were 21.98, 22.42, and 1,060. We concluded that a dose of 400 mg BID resulted in sustained plasma, ELF, and AC concentrations above the MIC 90 for Aspergillus spp. during the dosing interval. Confirmation of the therapeutic value of these observations requires further investigation. The intrapulmonary PKPD of POS may be favorable for treatment or prevention of aspergillosis, although further research on the relevant PKPD parameters and the effect of POS protein binding is required.Posaconazole (POS) is a new antifungal agent with activity against Aspergillus, Cryptococcus, Candida, Histoplasma, and Blastomyces spp. and others (9,15,17,19,27). POS is approved for prophylaxis of invasive aspergillosis and candidiasis in immunocompromised patients and for the treatment of refractory oropharyngeal candidiasis. Recent reports suggest that it may also be effective in the treatment of refractory invasive aspergillosis (16, 26), zygomycosis (23), and other fungal infections (3,18).The oral bioavailability of POS is increased by ingestion of a high-fat meal and by the use of divided dosing (8, 10). There are no clinically or kinetically important metabolites of POS. POS has a high apparent volume of distribution, 1,774 liters, and a prolonged half-life, 35 h, at steady state (G. Krishna and A. Sansone-Parsons, presented at the 41st American Society of Health System Pharmacists Midyear Clinical Meeting and Exhibition, Anaheim, CA, 3 to 7 December 2006). Its pharmacokinetics (PK) are unaffected by age, gender, or race/ethnicity (21), and dose correction is not required for patients with impaired renal function (7); 66.3% of an oral POS dose is excreted unchanged in feces (12). Protein binding in human plasma is Ͼ98%. We recently reported on the intrapulmonary pharmacokinetics and pharmacodynamics (PKPD) of POS in healthy subjects (5). Maximum concentration of drug in serum (C max ) values were 2.08, 1.86, ...

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Current Strategies in the Treatment of Fungal Infections in the Intensive Care Unit Setting

Goldman

Sarosi

2009

Pulmonary Infection in the Immunocompromised Patient

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Safety, Tolerance, and Efficacy of Posaconazole Therapy in Patients with Nonmeningeal Disseminated or Chronic Pulmonary Coccidioidomycosis

Cited by 111 publications

References 24 publications

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Recent Advances in Our Understanding of the Environmental, Epidemiological, Immunological, and Clinical Dimensions of Coccidioidomycosis

Steady-State Intrapulmonary Pharmacokinetics and Pharmacodynamics of Posaconazole in Lung Transplant Recipients

Current Strategies in the Treatment of Fungal Infections in the Intensive Care Unit Setting

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