Abstract

In view of the emergence of multidrug-resistant group B streptococci (GBS), and its significant clinical impact, there is a necessary need for the development of more effective therapeutic alternatives. Here, we assessed the therapeutic efficacy of daptomycin, a novel lipopeptide antibiotic, in the treatment of type IV GBS-induced invasive systemic infection and septic arthritis in mice. We also evaluated the possible synergy between daptomycin and fusidin to combat GBS disease. Mice infected with type IV  GBS and left without drug treatment displayed high incidence of deaths and severe diffuse septic arthritis, associated with excessive production of proinflammatory cytokines (tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6)), cyclooxygeanse-2 (COX-2) and prostaglandin E2 (PGE2) in their blood and joints. However, treatment of these GBS-infected mice with daptomycin significantly inhibited the inoculated bacteria to grow in the blood and joints. Daptomycin-treated mice had significantly showed lower mortality rates, less frequent arthritis and lower levels of TNF-α, IL-1β, IL-6, COX-2 and PGE2 than infected untreated animals. More interestingly, a marked in vivo synergy between daptomycin and fusidin that completely protected the mice from GBS infection and its associated mortality and serious sequels was clearly observed. In summary, the present study showed that daptomycin is a welcome newcomer antibacterial arsenal to eradicate GBS invasive infection and septic arthritis, in particular when given in combination with other antibacterial agents such as fusidin.

Key words: Group B streptococci, septic arthritis, daptomycin, fusidin, proinflammatory cytokines, cylooxygenase-2, prostaglandin E2.