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

Abstract

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 log l0 cfu/well after 20 h, against 4 log 10 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 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.

In VitroandIn VivoSynergistic Effects of Cryptdin 2 and Ampicillin against Salmonella

“…Interestingly, the killing effect was found to be more pronounced when both agents were used in combination to treat intracellular salmonellae. These results are in concordance with earlier reports wherein it was proposed that ampicillin kills intracellular salmonellae within mouse macrophages owing to its internalization by cells through pinocytosis (6,18). The fact that alphadefensins may enhance phagocytosis by interacting directly In support of our findings, defensins have been reported to enable macrophages to inhibit intracellular proliferation of Listeria (2).…”

Comparison of ofloxacin and ceftriaxone for short-course treatment of enteric fever

“…No patient in the ofloxacin group had fever for 7 days. This may reflect a greater intracellular activity of ofloxacin against S. typhi, although ceftriaxone and pefloxacin were shown to have comparable bactericidal activities in a human monocyte-derived macrophage model (9). Relapse rates may have been underestimated because of the relatively poor attendance for the follow-up examination.…”

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

“…Likewise, gentamicin kills intracellular Listeria monocytogenes within bactericidal and nonbactericidal peritoneal mouse macrophages, probably owing to its internalization by cells through pinocytosis (75). A similar mechanism has been proposed to explain the activity of ampicillin and ceftriaxone against Salmonella enterica serovar Typhi ingested by human monocytederived macrophages (52). The recognized importance of cellular accumulation for treating infections caused by intracellular pathogens has triggered novel strategies such as associating antibiotics with colloidal particulate carriers (liposomes or nanoparticles) to promote endocytosis (22,58).…”