title: Efficacy of caspofungin, a 1,3-β-D-glucan synthase inhibitor, on Pneumocystis carinii pneumonia in rats.
abstract: 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.
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao yang Hospital, Capital Medical University, Beijing, China Department of Pneumology, Peking University Shougang Hospital, Beijing, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao yang Hospital, Capital Medical University, Beijing, China tongzhh2012@126.com.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Tong
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001835:Body Weight / Q000187:drug effects; D000077336:Caspofungin; D054714:Echinocandins / Q000494:pharmacology* / Q000627:therapeutic use; D055666:Lipopeptides; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D045363:Pneumocystis carinii / Q000187:drug effects*; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D051381:Rats
chemical_list: D000935:Antifungal Agents; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin
keywords: 1,3-β-D-glucan synthase inhibitor; Pneumocystis carinii pneumonia; treatment