Abstract
BackgroundEvidence 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.MethodsTNF-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.ResultsGBS 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).ConclusionsCombination therapy of ampicillin+azithromycin improved outcomes in a murine GBS sepsis model; this therapeutic approach deserves additional study.
Highlights
Group B streptococci (GBS) have long been recognized as a leading cause of infections in neonates, young infants, and pregnant women [1, 2]
group B streptococcal (GBS) isolates exposed to azithromycin or combination stimulated less TNF production in vitro
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
Summary
Group B streptococci (GBS) have long been recognized as a leading cause of infections in neonates, young infants, and pregnant women [1, 2]. The general goal of treatment has been to eliminate pathogens as rapidly as possible, so bactericidal agents have been preferred. These bactericidal antibiotics cause rapid release of bacterial cell wall and other components, which may result in an augmented and potentially harmful systemic inflammatory response [12,13]. These exaggerated proinflammatory responses in the context of overwhelming GBS infection may contribute to many of the manifestations of GBS diseases including high morbidity and mortality. 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
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