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 degrees 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 (less than 0.25 log10 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 (10 mg/l) did not exhibit any significant antibacterial effect, indicating that most or all the bacteria recovered from lysed 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.
Chang
H R
HR
Department of Microbiology, University of Geneva Medical School, C.M.U., Switzerland.
Vladoianu
I R
IR
Pechère
J C
JC
D000667:Ampicillin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002443:Ceftriaxone / Q000494:pharmacology; D002701:Chloramphenicol / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000382:microbiology; D015366:Pefloxacin / Q000494:pharmacology; D012483:Salmonella Phages; D012485:Salmonella typhi / Q000187:drug effects*; D015662:Trimethoprim, Sulfamethoxazole Drug Combination / Q000494:pharmacology; D014343:Trypan Blue
D000900:Anti-Bacterial Agents; D015366:Pefloxacin; D002701:Chloramphenicol; D002443:Ceftriaxone; D000667:Ampicillin; D015662:Trimethoprim, Sulfamethoxazole Drug Combination; D014343:Trypan Blue