Efficacy of caspofungin, a 1,3-β-D-glucan synthase inhibitor, on Pneumocystis carinii pneumonia in rats.

Pneumocystis carinii pneumonia (PcP) is a common and potentially fatal opportunistic infection in immunosuppressed patients, and the standard trimethoprim-sulfamethoxazole (TMP-SMZ) treatment has serious side effects. The cell wall of the causative fungal pathogen is enriched in 1-3-β-D-glucan, providing an alternative therapeutic target. We directly compared the efficacy of the 1,3-β-D-glucan synthase inhibitor caspofungin to TMP-SMZ for promoting survival and reducing lung cyst number during the early phase of treatment in a rat model of PcP. Rats were immunosuppressed using dexamethasone for 8 weeks and PcP infection confirmed in test animals by lung print smear. The remaining rats were randomly divided into three control groups, a baseline group and two observed for 7 or 14 days, two caspofungin groups treated intravenously for 7 or 14 days (1 mg/kg/d), and 2 TMP-SMZ positive control groups treated by oral gavage for 7 or 14 days (300 mg/kg/d). Mortality was markedly reduced by both caspofungin and TMP-SMZ after 14 days (caspofungin: 20.0%, TMP-SMZ: 13.3%, Control: 40.0%). Body weight gain in caspofungin-treated rats after 7 (3.04 ± 3.54%) and 14 (4.27 ± 2.79%) days was similar to that in TMP-SMZ-treated rats (3.35 ± 1.88% and 5.85 ± 2.78%, respectively), whereas untreated controls showed weight loss. Lung weight to body weight ratio, and mean cyst number per 50 microscopic fields were significantly lower (all P < 0.05) in caspofungin-treated rats than untreated controls at both 7 and 14 days, and similar to those in the TMP-SMZ-treated rats (all P > 0.05 vs. caspofungin). Caspofungin exhibited similar efficacy to TMP-SMZ for enhancing survival and reducing lung edema and cyst load in a rat model of PcP, suggesting potential clinical utility against PcP.

Sun P ，Tong Z 《-》

[The treatment of pneumocystis Carinii pneumonia with caspofungin in elderly patients: a case report and literature review].

Zhang JC ，Dai JY ，Fan J ，Wu XP ... -  《-》

High initial (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory response of c aspofungin combined with TMP/SMZ for HIV-negative patients with moderate to severe Pneumocystis jirovecii pneumonia.

The aim of this study was to investigate the efficacy of combination therapy of caspofungin and TMP/SMZ (trimethoprim/sulfamethoxazole) in moderate to severe pneumocystis jirovecii pneumonia (PJP) in patients without human immunodeficiency virus infection (HIV) and the relationship between therapeutic effect and plasma (1, 3) Beta-d-Glucan (BDG) levels. We retrospectively reviewed HIV-negative patients with PJP diagnosed in our department, who were treated with combination therapy of caspofungin and TMP/SMZ or monotherapy of TMP/SMZ during a six and a half year period. A total of 126 moderate to severe PJP patients were enrolled in the study. In the multivariate analysis, low lymphocyte counts, high serum lactate dehydrogenase levels at the diagnosis of PJP and progression to shock were significant risk factors for death. In all patients, there was no significant difference in risk of death at 3 months. In the group of BDG≥800pg/m, patients receiving combination therapy was associated with a significantly decreased risk of death at 3 months, whereas in the group of BDG<800pg/ml, there were no statistically significant difference in survival rate between the two treatment regimens. High initial plasma (1, 3) Beta-d-Glucan concentration may be a predictor of satisfactory caspofungin response to HIV-negative patients with PJP. Based on our findings, we suggest the choice of combination therapy with caspofungin and TMP/SMZ as the initial treatment when BDG≥800pg/ml in moderate to severe HIV-negative patients with PJP.

Jin F ，Liu XH ，Chen WC ，Fan ZL ，Wang HL ... -  《-》

Successful treatment of severe Pneumocystis pneumonia in an immunosuppressed patient using caspofungin combined with clindamycin: a case report and literature review.

Li H ，Huang H ，He H 《BMC Pulmonary Medicine》

[Study on the changes of soluble intercellular adhesion molecule-1 level in sera of rats infected with Pneumocystis carinii].

Liu KQ ，Yin WD ，Xue GP ，Zhang JS ... -  《-》