Improved survival in the suckling rat model of group B streptococcal sepsis after treatment with nonsteroidal anti-inflammatory drugs

Abstract

The nonsteroidal anti-inflammatory drugs, indomethacin and ibuprofen, have been shown to increase survival in various animal models of Gram-negative or endotoxin shock. To evaluate the use of these drugs in group B streptococcal sepsis, a clinically similar disease state, a newborn suckling rat model (4 to 5 days old) designed to simulate early-onset group B streptococcal sepsis was used. Sepsis was induced by a subcutaneous injection of group B streptococcal organisms (type III). A mortality ranging from 30% to 90% was used for the study. Indomethacin (3 mg/kg) or ibuprofen (4 mg/kg) treatment was administered by an intraperitoneal injection either at the time of the bacterial injection or after bacteremia (four hours) had occurred. Indomethacin clearly improved survival rates, even when given after bacteremia. Ibuprofen also clearly increased survival when given at the same time as the bacterial injection. Ibuprofen was more effective than indomethacin in the high mortality model (lethal dose for 90% survival of group). These drugs alter mechanisms that may be important in the irreversibility of sepsis and they may become useful adjuvants to our present treatment of early onset group B streptococcal sepsis.