Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451).
Benanomicin A (BNM-A) has antimycotic activities via binding to mannan in the cell walls of fungi. Anti-Pneumocystis carinii activity of the agent was examined in the P. carinii-infected BALB/c nu/nu female mouse model because P. carinii also possesses mannan in the membranes. The infected mice were treated with intraperitoneal injections of six doses of BNM-A (1, 2.5, 5, 10, 30, and 100 mg/kg of body weight), 4 mg of pentamidine isethionate per kg, 100 mg of sulfamethoxazole per kg combined with 20 mg of trimethoprim per kg (co-trimoxazole), or saline for 21 days. Each dosage group consisted of 10 mice. During treatment, five mice in the control group (saline) died, whereas 8 to 10 mice in all treatment groups survived. Almost the same efficacies were obtained for the groups treated with 5 mg or more and 10 mg or more of BNM-A per kg regarding the weight and number, respectively, of cysts found in the lungs as were obtained for the groups treated with pentamidine isethionate and co-trimoxazole. Overall, a dose of 10 mg of BNM-A per kg was effective against P. carinii pneumonia infection in the mice. Thus, BNM-A is a good candidate for a novel treatment for P. carinii pneumonia as a compound with a new mechanism of action against P. carinii.
Yasuoka
A
A
Department of Infectious Diseases, University of Tokyo, Japan.
Oka
S
S
Komuro
K
K
Shimizu
H
H
Kitada
K
K
Nakamura
Y
Y
Shibahara
S
S
Takeuchi
T
T
Kondo
S
S
Shimada
K
K
D000818:Animals; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000935:Antifungal Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D005260:Female; D008168:Lung / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009929:Organ Size / Q000187:drug effects; D010419:Pentamidine / Q000494:pharmacology; D011020:Pneumonia, Pneumocystis / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D000095643:Pradimicins and Benanomicins
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D000935:Antifungal Agents; D010419:Pentamidine; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; C056805:benanomicin A; D000095643:Pradimicins and Benanomicins