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Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

Wlaź P, Knaga S, Kasperek K, Wlaź A, Poleszak E, Jeżewska-Witkowska G, Winiarczyk S, Wyska E, Heinekamp T, Rundfeldt C - Mycopathologia (2015)

Bottom Line: Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow.Inhalation of 4 % ITRA nanosuspension was less effective.Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland, piotr.wlaz@umcs.lublin.pl.

ABSTRACT
Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier survival curve (a) and cumulative disease score (b) of groups of quails inoculated intratracheally with 5 × 107 spores of A. fumigatus (n = 10/group). A cumulative disease score was generated by adding up all scores of all animals on the respective day. For statistical analysis of the resulting group disease score, the area under the score curve (AUC) was calculated and compared using the Chi-square test with α-adjustment for multiple comparisons (inserted table)
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Fig3: Kaplan–Meier survival curve (a) and cumulative disease score (b) of groups of quails inoculated intratracheally with 5 × 107 spores of A. fumigatus (n = 10/group). A cumulative disease score was generated by adding up all scores of all animals on the respective day. For statistical analysis of the resulting group disease score, the area under the score curve (AUC) was calculated and compared using the Chi-square test with α-adjustment for multiple comparisons (inserted table)

Mentions: The treatment with ITRA nanosuspension (4 and 10 % suspension) resulted in a retarded disease development. While the treatment effect was found to be highly significant for the disease score development for both treatment groups, the improvement in survival was small and did not reach the level of significance. With both treatments, no complete protection from lethality was obtained. No clear dose response for the survival could be observed, but there was a tendency that the disease score was lower in the 10 % group as compared to the 4 % group (Fig. 3a, b). Gross pathology of animals which had died and in those which had survived until day 8 was not different from vehicle-treated animals.Fig. 3


Activity and Safety of Inhaled Itraconazole Nanosuspension in a Model Pulmonary Aspergillus fumigatus Infection in Inoculated Young Quails.

Wlaź P, Knaga S, Kasperek K, Wlaź A, Poleszak E, Jeżewska-Witkowska G, Winiarczyk S, Wyska E, Heinekamp T, Rundfeldt C - Mycopathologia (2015)

Kaplan–Meier survival curve (a) and cumulative disease score (b) of groups of quails inoculated intratracheally with 5 × 107 spores of A. fumigatus (n = 10/group). A cumulative disease score was generated by adding up all scores of all animals on the respective day. For statistical analysis of the resulting group disease score, the area under the score curve (AUC) was calculated and compared using the Chi-square test with α-adjustment for multiple comparisons (inserted table)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4498244&req=5

Fig3: Kaplan–Meier survival curve (a) and cumulative disease score (b) of groups of quails inoculated intratracheally with 5 × 107 spores of A. fumigatus (n = 10/group). A cumulative disease score was generated by adding up all scores of all animals on the respective day. For statistical analysis of the resulting group disease score, the area under the score curve (AUC) was calculated and compared using the Chi-square test with α-adjustment for multiple comparisons (inserted table)
Mentions: The treatment with ITRA nanosuspension (4 and 10 % suspension) resulted in a retarded disease development. While the treatment effect was found to be highly significant for the disease score development for both treatment groups, the improvement in survival was small and did not reach the level of significance. With both treatments, no complete protection from lethality was obtained. No clear dose response for the survival could be observed, but there was a tendency that the disease score was lower in the 10 % group as compared to the 4 % group (Fig. 3a, b). Gross pathology of animals which had died and in those which had survived until day 8 was not different from vehicle-treated animals.Fig. 3

Bottom Line: Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow.Inhalation of 4 % ITRA nanosuspension was less effective.Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity.

View Article: PubMed Central - PubMed

Affiliation: Department of Animal Physiology, Institute of Biology and Biochemistry, Faculty of Biology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, PL-20033, Lublin, Poland, piotr.wlaz@umcs.lublin.pl.

ABSTRACT
Pulmonary aspergillosis is frequently reported in parrots, falcons, and other birds held in captivity. Inhalation is the main route of infection for Aspergillus fumigatus, resulting in both acute and chronic disease conditions. Itraconazole (ITRA) is an antifungal commonly used in birds, but its administration requires repeated oral dosing, and the safety margin is narrow. To investigate the efficacy of inhaled ITRA, six groups of ten young quails (Coturnix japonica) were inoculated intratracheally with 5 × 10(6) spores (3 groups) or 5 × 10(7) spores (3 groups). Animals were exposed to nebulized ITRA nanosuspension as 10 % suspension or 4 % suspension, once daily for 30 min, starting 2 h after inoculation for 6 days. Control groups were exposed to nebulized saline for the same period of time. Survival and clinical scores were evaluated, and animals were subjected to gross pathology. In control animals, aspergillosis resulted in systemic disease without pulmonary or air sac granulomas. Animals died from multiple organ failure. Inhalation of 10 % ITRA nanosuspension blocked lethality and prevented disease-related symptoms in the quails exposed to the low dose of spores, while the disease course in quails inoculated with the high-spore dose was retarded. Inhalation of 4 % ITRA nanosuspension was less effective. Both inhalations were well tolerated, and gross pathology did not reveal signs of local toxicity. The data indicate that inhaled administration of 10 % ITRA nanosuspension is capable of alleviating an acute A. fumigatus infection in quails. A lower ITRA concentration may be only active in chronic pulmonary aspergillosis.

No MeSH data available.


Related in: MedlinePlus