Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice.
Therapeutic potential of caspofungin combined with trimethoprim-sulfamethoxazole for pneumocystis pneumonia: a pilot study in mice.
复制标题
DOI：
10.1371/journal.pone.0070619
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Matos O
中科院分区：
文献类型：
--
作者：
Lobo ML;Esteves F;de Sousa B;Cardoso F;Cushion MT;Antunes F;Matos O
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 14th 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.
登录
查看更多内容
影响因子：
14.2
作者：
Esteves, F.;Gaspar, J.;Matos, O.
通讯作者：
Matos, O.
影响因子：
4.9
作者：
Powles, MA;Liberator, P;Schmatz, D
通讯作者：
Schmatz, D
影响因子：
2.4
作者：
Hufeldt, M. R.;Nielsen, D. S.;Hansen, A. K.
通讯作者：
Hansen, A. K.
影响因子：
9.4
作者：
Persat, Florence;Ranque, Stephane;Sulahian, Annie
通讯作者：
Sulahian, Annie
影响因子：
1
作者：
Beltz, K.;Kramm, C. M.;Goebel, U.
通讯作者：
Goebel, U.