In vitro evaluation of intracellular activity of antibiotics against non-typhoid Salmonella

Abstract

Non-typhoid salmonellae are the most common causative organisms of bacterial enteritis in children. Clinical studies have failed to show any influence of various antibiotics on the natural course of acute salmonella enteritis. Poor penetration of antibiotics into phagocytic cells that contain intracellular Salmonella spp., and possible intracellular antibiotic inactivation have been considered as possible reasons for this. In this study, we used an in vitro model to assess the intracellular activity of antibiotics against non-typhoid salmonellae. The survival of intracellular Salmonella spp. in P388D1 cells, a mouse macrophage cell line was measured in the presence of various antibiotics. Except for gentamicin, which entered phagocytes poorly, ofloxacin, azithromycin, chloramphenicol and three beta-lactam antibiotics, ampicillin, cefixime and ceftriaxone, exhibited bacteriostatic activity against susceptible intracellular Salmonella spp. at an extracellular concentration equal to the minimal inhibitory concentration (MIC). At a concentration of 10 x MIC, neither chloramphenicol nor the three beta-lactam antibiotics produced a bactericidal response; however, both ofloxacin and azithromycin were bactericidal after 8-24 h of incubation. The results showed that fluoroquinolones and new macrolides were more efficient than the other antibiotics in eradicating intracellular salmonella and might be useful agents for the treatment of non-typhoid salmonella enteritis in children. Clinical trials should be considered.