Nebulized voriconazole in infections with Scedosporium apiospermum — Case report and review of the literature

Holle, Julia; Leichsenring, M.; Meißner, Peter

doi:10.1016/j.jcf.2013.10.014

Cited by 29 publications

(21 citation statements)

References 7 publications

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“…The finding of roughly 8 times higher concentrations in ELF than in plasma after oral administration are consistent with the results of a previous study in human beings after intravenous administration [7]. However, due to the effectiveness of the inhaled 40mg dose that was previously observed [2,8], it was expected that the concentrations of voriconazole in ELF after inhalation would be closer to the ELF concentrations after oral ingestion. Even though there was a tendency for the ELF/plasma ratio to be higher after inhalation, it was not significant.…”

Section: Discussionsupporting

confidence: 90%

“…In ELF, median concentration was 190 (55-318) ng/mL and 8827 (4369-35172) ng/mL, respectively (p < 0.0001). Median ELF/plasma concentration ratio was 21 (6-63) in the inhalation group and 8 (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) in the oral group (p = 0.2). In conclusion, voriconazole is rapidly absorbed into the systemic circulation after inhalation.…”

mentioning

confidence: 96%

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Voriconazole Concentrations in Plasma and Epithelial Lining Fluid after Inhalation and Oral Treatment

Andersen

Sønderskov

Bendstrup

et al. 2017

Basic Clin Pharma Tox

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Adverse effects can compromise oral voriconazole treatment of pulmonary aspergillosis. Inhaled low-dose voriconazole may be an alternative treatment. In this study, six patients inhaled 40 mg voriconazole b.i.d. for 2 days, and six patients ingested 400 and 200 mg orally b.i.d. on day one and two, respectively. Blood samples were collected after the first inhalation, and bronchial alveolar lavage fluids and blood samples were collected for measurements of voriconazole 12 hr after the last administration. The concentration of voriconazole in epithelial lining fluid (ELF) was calculated by the urea dilution method. Voriconazole concentrations were detectable in plasma 15 min. after inhalation and declined at 30 and 60 min. Twelve hours after the last dose, median (95% CI) plasma voriconazole concentration was 8 (4-26) ng/mL in the inhalation group and 1224 (535-2341) ng/mL in the oral group (p < 0.0001). In ELF, median concentration was 190 (55-318) ng/mL and 8827 (4369-35172) ng/mL, respectively (p < 0.0001). Median ELF/plasma concentration ratio was 21 (6-63) in the inhalation group and 8 (3-20) in the oral group (p = 0.2). In conclusion, voriconazole is rapidly absorbed into the systemic circulation after inhalation. There was a non-significant trend towards a higher ELF/plasma concentration ratio in the inhalation group compared to the oral group.

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Section: Discussionsupporting

confidence: 90%

mentioning

confidence: 96%

Voriconazole Concentrations in Plasma and Epithelial Lining Fluid after Inhalation and Oral Treatment

Andersen

Sønderskov

Bendstrup

et al. 2017

Basic Clin Pharma Tox

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“…Posaconazole was found effective against S. apiospermum complex members in vitro. According to in vivo studies (murine models) and patient case reports, this drug is effective (34)(35)(36)(37), but in vitro susceptibility testing is mandatory due to the occurrence of resistance. Anidulafungin and micafungin may represent future therapeutic options, which, however, remain to be evaluated by in vivo experiments.…”

Section: Discussionmentioning

confidence: 99%

Susceptibility and Diversity in the Therapy-Refractory Genus Scedosporium

Lackner

Hagen

Meis

et al. 2014

Antimicrob Agents Chemother

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Scedosporium species show decreased susceptibility to the majority of systemic antifungal drugs. Acquired resistance is likely to disseminate differentially with the mode of exchange of genetic material between lineages. Inter-and intraspecific diversities of Scedosporium species were analyzed for three partitions (rDNA internal transcribed spacer gene [ITS], partial ␤-tubulin gene, and amplified fragment length polymorphism profiles), with the aim to establish distribution of resistance between species, populations, and strains. Heterogeneity of and recombination between lineages were determined, and distances between clusters were calculated using a centroid approach. Clinical, geographic, and antifungal data were plotted on diversity networks. Scedosporium minutisporum, Scedosporium desertorum, and Scedosporium aurantiacum were distinguished unambiguously in all partitions and had differential antifungal susceptibility profiles (ASP). Pseudallescheria fusoidea and Pseudallescheria ellipsoidea were indistinguishable from Scedosporium boydii. Pseudallescheria angusta took an intermediate position between Scedosporium apiospermum and S. boydii. Scedosporium boydii and S. apiospermum had identical ASP. Differences in (multi)resistance were linked to individual strains. S. apiospermum and S. boydii showed limited interbreeding and were recognized as valid, sympatric species. The S. apiospermum/S. boydii group, comprising the main clinically relevant Scedosporium species, consists of separate lineages and is interpreted as a complex undergoing sympatric evolution with incomplete lineage sorting. In routine diagnostics, the lineages in S. apiospermum/S. boydii are indicated with the umbrella descriptor "S. apiospermum complex"; individual species can be identified with rDNA ITS with 96.3% confidence. Voriconazole is recommended as the first-line treatment; resistance against this compound is rare.

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“…Aerosolized medication regimens are an attractive option because drug interactions and systemic toxicities are likely limited . Several centers have reported on the safety of aerosolized AmB deoxycholate using a variety of dosing regimens; others, using aerosolized AmB lipid formulations or inhaled voriconazole . However, there are many potential issues with inhalation therapy (dose, devices, pulmonary deposition) that require consideration prior to its use.…”

Section: Discussionmentioning

confidence: 99%

“…The literature available for inhaled antifungals in humans, other than AmB, is scarce. The role of inhaled voriconazole therapy in invasive aspergillosis and scedosporiosis management has recently been published …”

Section: Introductionmentioning

confidence: 99%

Salvage therapy with topical posaconazole in lung transplant recipients with invasive Scedosporium infection

Solé

García-Robles

Jordá

et al. 2018

American Journal of Transplantation

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Scedosporium is an important pathogen in cystic fibrosis (CF) and post-transplantation, but it rarely causes invasive infection. Treatment remains challenging, particularly due to the inherent resistance to multiple antifungal agents. We present 3 complicated invasive tracheobronchial and lung Scedosporium apiospermum infections following lung transplantation. In 2 of 3 cases, the infection was clinically and radiologically cured with frequent cleansing bronchoscopies, combining triazole with terbinafine therapy and nebulized posaconazole. These cases highlight the importance of adjunctive nebulized therapy in addition to prolonged triazole treatment to manage complex invasive Scedosporium infections in immunosuppressed patients. Posaconazole (PSZ) was delivered during the bronchoscopy procedure through intrabronchial administration, whereas an eFlow rapid device was used for nebulized therapy. Topical posaconazole was well tolerated in 2 patients, with only a slight cough during administrations; the third patient had local irritation with poor tolerance, which led to its withdrawal. This is the first report on compassionate use of topical PSZ as salvage therapy for resistant mold infections in lung transplant recipients. These 3 cases represent the entire experience using this approach; no additional patients have received this therapy due to there not having been any additional cases of Scedosporium tracheobronchitis presented.

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Nebulized voriconazole in infections with Scedosporium apiospermum — Case report and review of the literature

Cited by 29 publications

References 7 publications

Voriconazole Concentrations in Plasma and Epithelial Lining Fluid after Inhalation and Oral Treatment

Voriconazole Concentrations in Plasma and Epithelial Lining Fluid after Inhalation and Oral Treatment

Susceptibility and Diversity in the Therapy-Refractory Genus Scedosporium

Salvage therapy with topical posaconazole in lung transplant recipients with invasive Scedosporium infection

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