EFFECT OF ANTIMICROBIAL CLASS ON THE HOST INFLAMMATORY RESPONSE TO STREPTOCOCCUS PYOGENES.

Abstract

Background Penicillin (PEN) has been the time-honored therapy for infections caused by Streptococcus pyogenes (group A streptococcus [GAS]). However, PEN alone is not considered adequate therapy for severe GAS soft tissue infections because of the “Eagle effect” (efficacy of clindamycin [CLI] or erythromycin but not PEN in severe soft tissue infection in animal models). The mechanisms responsible for the Eagle effect are poorly understood but may include a blunted host cytokine response to GAS. Purpose We sought to determine whether exposure of macrophages to GAS in the presence of CLI, daptomycin (DAP), linezolid (LZD), or vancomycin (VAN) (compared with PEN) resulted in reduced tumor necrosis factor (TNF) secretion. Methods RAW 264.7 murine macrophages were exposed to a live M1T1 isolate of S. pyogenes (106 cfu/mL) in the presence of either DAP, PEN, CLI, VAN, LZD, or various combinations of these antibiotics for 16 to 18 hours. After incubation, cell supernatants were collected and assayed for TNF concentration by ELISA. Results We found that RAW 264.7 cells secreted more TNF when exposed to the M1T1 isolate in the presence of PEN (compared with any of the other antibiotics). Exposure of the isolate to DAP led to substantially less macrophage TNF secretion (compared with PEN or any of the other antibiotics: 40% less than PEN, 39% less than LZD, 33% less than CLI, and 19% less than VAN, p Conclusions We found that exposure of an M1T1 isolate of GAS to DAP (alone or in combination with PEN) consistently resulted in reduced secretion of TNF by macrophages (compared with exposure of the organism to PEN or the other comparator antibiotics). Treatment of severe GAS soft tissue infections with DAP alone or in combination with PEN may result in less intense inflammation compared with other therapies. This possibility should be examined in animal models of GAS soft tissue infection similar to those performed by Eagle and colleagues.