beta-Lactams have been considered ineffective against organisms growing inside mammalian cells because of their poor penetration into cells. However,
cefixime has been shown to be clinically effective against
typhoid fever. The probable mechanism of therapeutic effectiveness of
cefixime against
typhoid fever was investigated using Salmonella enterica serovar Typhimurium instead of S. enterica serovar Typhi both in a cellular and in a mouse
infection model.
Cefixime was able to inhibit the growth of serovar Typhimurium inhabiting monocyte-derived THP-1 cells. Elongation of serovar Typhimurium in THP-1 cells was observed microscopically. Apparent morphological changes of serovar Typhimurium in THP-1 cells were also observed by electron microscopy. The concentration of
cefixime inside THP-1 cells was almost half (46 to 48%) of the concentration outside the cells when serovar Typhimurium coexisted in the
solution. The length of time after oral dosing (8 mg/kg) that
cefixime was present-calculated from levels in serum-at a concentration above the MIC at which 90% of the serovar Typhi organisms inside human cells were inhibited was presumed to be more than 12 h.
Cefixime also showed excellent activity in the mouse systemic and oral
infection models based on
infections caused by serovar Typhimurium. It is concluded that a fair amount of
cefixime can enter mammalian cells and inhibit the growth of bacteria inside cells when the bacteria are sensitive enough to
cefixime, as are serovars Typhimurium and Typhi.