Please use this identifier to cite or link to this item:
https://hdl.handle.net/10316/46919
DC Field | Value | Language |
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dc.contributor.author | Lobo, Maria Luísa | - |
dc.contributor.author | Esteves, Francisco | - |
dc.contributor.author | Sousa, Bruno de | - |
dc.contributor.author | Cardoso, Fernando | - |
dc.contributor.author | Cushion, Melanie T. | - |
dc.contributor.author | Antunes, Francisco | - |
dc.contributor.author | Matos, Olga | - |
dc.date.accessioned | 2018-01-26T18:41:55Z | - |
dc.date.available | 2018-01-26T18:41:55Z | - |
dc.date.issued | 2013 | - |
dc.identifier.uri | https://hdl.handle.net/10316/46919 | - |
dc.description.abstract | Pneumocystis pneumonia (PcP) is a major cause of mortality and morbidity in immunocompromised patients. There are limited alternative therapeutic choices to trimethoprim-sulfamethoxazole (TMP-SMX) which is the standard first line therapy/prophylaxis for PcP. The efficacy of low doses of caspofungin and caspofungin in association with TMP-SMX standard-prophylactic dose was evaluated in an experimental model of Pneumocystis. Susceptibility of Pneumocystis spp. to low doses of caspofungin and caspofungin/TMP-SMX was evaluated in Balb/c immunosuppressed mice, infected intranasally with P. murina. Caspofungin was administered once daily at 0.1 mg/kg, 0.05 mg/kg, and 0.001 mg/kg and TMP-SMX was administered by oral gavage (12.25 mg/62.5 mg/day), for 21 days. Efficacy was calculated based on the reduction in organism burden determined through quantitative fluorescent-based real-time PCR (qPCR). Serum β-1,3-D-glucan was measured as an additional marker of infection. The present data showed that caspofungin demonstrated anti-Pneumomocystis effect. However, the doses administrated were too low to achieve Pneumocystis eradication, which suggests that echinocandin treatment should not be administrated as mono-therapy. After 21 days of treatment, P. murina was not detected in the lungs of mice with either TMP-SMX or caspofungin/TMP-SMX. The results showed that, even at the lowest concentrations tested, the efficacy of caspofungin in association with TMP-SMX was higher than the efficacy of either drug used alone. The administration of caspofungin/TMP-SMX was at least 1.4 times more effective against P. murina infection than TMP-SMX used alone. The most promising result was achieved with the combination of caspofungin 0.05 mg/kg/day with TMP-SMX 12.5 mg-62.5 mg/day, which reduced the parasite burden to undetectable levels immediately at the 14(th) day of treatment, showing a highly marked anti-Pneumomocystis effect. These data suggest that the administration of low doses of caspofungin in combination with low doses of TMP-SMX may provide an improved treatment protocol for Pneumocystis infection clearance. | por |
dc.language.iso | eng | por |
dc.rights | openAccess | por |
dc.subject | Animals | por |
dc.subject | Disease Models, Animal | por |
dc.subject | Drug Combinations | por |
dc.subject | Echinocandins | por |
dc.subject | Lipopeptides | por |
dc.subject | Male | por |
dc.subject | Mice | por |
dc.subject | Mice, Inbred BALB C | por |
dc.subject | Pneumonia, Pneumocystis | por |
dc.subject | Trimethoprim, Sulfamethoxazole Drug Combination | por |
dc.title | Therapeutic Potential of Caspofungin Combined with Trimethoprim-Sulfamethoxazole for Pneumocystis Pneumonia: A Pilot Study in Mice | por |
dc.type | article | por |
degois.publication.firstPage | e70619 | por |
degois.publication.issue | 8 | por |
degois.publication.title | PLoS ONE | por |
dc.identifier.doi | 10.1371/journal.pone.0070619 | - |
degois.publication.volume | 8 | por |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | article | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | open | - |
item.fulltext | Com Texto completo | - |
item.languageiso639-1 | en | - |
crisitem.author.researchunit | Center for Research in Neuropsychology and Cognitive Behavioral Intervention | - |
crisitem.author.orcid | 0000-0001-9918-8100 | - |
crisitem.author.orcid | 0000-0001-7932-1154 | - |
crisitem.author.orcid | 0000-0001-5793-7716 | - |
Appears in Collections: | I&D CINEICC - Artigos em Revistas Internacionais |
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2013_Lobo_et_al.PDF | 251.09 kB | Adobe PDF | View/Open |
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