-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 monocytederived 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.
AbstrakAktivy'as in viÛo berbagai antibiotika termasuk sefiksim terhadap 73 isolat k/lnis Salmonella typhi dari berbagai srtmber telah dievaluasi menggunakan ,netoda dilusi agar konvensional dan Etest. I I dari 73
The binding of five structurally diverse β-lactam antibiotics to penicillin-binding proteins (PBPs) of two clinical isolates of Streptococcus pneumoniae resistant to penicillin G was compared with that of a susceptible strain. A common feature of the PBP patterns of the resistant strains was the absence of PBP la detected in the susceptible strain. For each β-lactam antibiotic tested, there appeared to be significant decreases in the affinity for BPB 1b, 2a and 2b of the resistant strains. We attempted to evaluate a quantitative correlation between the antibacterial activity of the drugs for three strains and their affinity for the various PBPs. A close correlation was found between the minimum inhibitory concentrations and the affinity for PBP 2a, but not for any of the other PBPs.
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