Effects of ampicillin, ceftriaxone, chloramphenicol, pefloxacin and trimethoprim-sulphamethoxazole on Salmonella typhi within human monocyte-derived macrophages

The killing effect of various antimicrobial agents used in the therapy of Salmonella typhi infection was tested against Salm. typhi strain Ty2 after phagocytosis by human monocyte-derived macrophages. The macrophages, cultured in 96-well microtitre plates, were infected for 1 h at 37°C by opsonized Salm. typhi Ty2 at a bacteria-cell ratio of 9:1. When added to the infected macrophage monolayers, at one and ten times the MIC, ampicillin, ceftriaxone and pefloxacin appeared to be highly bactericidal (< 0.25 logl0 cfu/well after 20 h, against 4 log10 cfu/well in antibiotic-free controls). Trimethoprim-sulphamethoxazole was bactericidal at ten times the MIC, but not at the MIC. Chloramphenicol was mostly bacteriostatic at the concentrations tested. As a control, gentamicin (10mg/l) did not exhibit any significant antibacterial effect, indicating that most or all the bacteria recovered from lyied cells were intracellular. Other controls for phagocytosis were also performed with heat-killed Candida albicans. Our results seem to correlate with the known clinical effect of some antimicrobials in human Salm. typhi infection. The in-vitro assay described here may be useful for assessing the activity of antimicrobial agents against Salm. typhi infection.