Journal Article

Combination therapy with ampicillin and azithromycin improved outcomes in a mouse model of group B streptococcal sepsis

Hiregoudar, Basu, English, Boyce Keith, Meals, Elizabeth, Talati, Ajay J., Upadhyay, Kirtikumar

2017

Overview

Evidence suggests that β-lactam monotherapy of streptococcal infections may incite stronger inflammation and is inferior to combination therapy with macrolides. We hypothesized that use of macrolides alone or in combination with a β-lactam for group B streptococcal (GBS) sepsis would improve outcomes by reducing inflammation. TNF-α was measured from supernatants of RAW 264.7 cells stimulated with GBS isolates, in presence of four treatment regimens: ampicillin alone, azithromycin alone, or combination of azithromycin plus ampicillin. Mouse model of GBS sepsis was developed and treated with same four regimens. Clinical sepsis scores were monitored; serum cytokines (TNF-α, IL-6, IL-10) and chemokines (MIP-1α) were measured at the end. GBS isolates exposed to azithromycin or combination (compared to ampicillin alone) stimulated less TNF production in vitro. In the murine sepsis model, mortality was lower along with decreased sepsis scores in mice treated with combination therapy. Mean serum IL-6 was lower in mice treated with azithromycin alone (66±52 pg/ml) or combination of ampicillin plus azithromycin (52±22 pg/ml) compared to ampicillin alone (260±160 pg/ml) (p<0.005). Combination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Amides / Ampicillin / Ampicillin - administration & dosage / Ampicillin - therapeutic use / Animals / Anti-Bacterial Agents - administration & dosage / Anti-Bacterial Agents - therapeutic use / Antibiotics / Antimicrobial agents / Azithromycin / Azithromycin - administration & dosage / Azithromycin - therapeutic use / Biology and Life Sciences / Cell Line / Chemokines / Combination drug therapy / Combination therapy / Cytokines / Cytokines - blood / Departments / Disease / Dosage and administration / Drug therapy / Drug Therapy, Combination / Female / Hospitals / In vitro methods and tests / Interleukin 10 / Interleukin 6 / Laboratory animals / Measurement methods / Medicine and Health Sciences / Meningitis / Mice / Mortality / Patient outcomes / Pediatrics / Penicillin / Pneumonia / Research and Analysis Methods / Science / Sepsis / Sepsis - drug therapy / Streptococcal Infections - drug therapy / Streptococcus / Streptococcus infections / Therapy / Tumor necrosis factor / Variance analysis