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Published on: August 11, 2014
In vitro effects of cefotaxime and ceftriaxone on Salmonella typhi within human monocyte-derived macrophages
Abstract:
The main objective of this in vitro study was to assess the effects of cefotaxime and ceftriaxone in killing Salmonella typhi in infected human macrophages. Human monocyte-derived macrophages isolated from peripheral blood of human volunteers were cultured in vitro for macrophage differentiation, and subsequently infected with S. typhi strains (a clinical isolate and a standard strain TA-42) at a cell ratio of 10 : 1. MICs of cefotaxime and ceftriaxone were determined by broth microdilution, and the antibiotics were included in the culture medium at one and five times their MIC values. Samples of cell culture medium taken at 0, 3, 6 and 24 h of incubation were cultured for growth of S. typhi on nutrient agar. Gentamicin (10 mg/L) was included in each well except for the control wells, in order to prevent growth of extracellular S. typhi. Both antibiotics showed good in vitro antibacterial effects against S. typhi strains. There were no statistically significant differences between the extracellular and intracellular effects of antibiotics with regard to elimination of the bacteria. Cefotaxime and ceftriaxone are highly effective against extracellular bacterial growth. The results of our in vitro experiments suggest that cefotaxime and ceftriaxone might also be used clinically against susceptible intracellular pathogens such as S. typhi.
Insights
Cefotaxime and ceftriaxone effectively kill Salmonella typhi within human macrophages in vitro. These antibiotics demonstrate potent activity against both extracellular and intracellular bacteria, suggesting clinical utility for treating typhoid fever.
Area of Science:
- Microbiology
- Immunology
- Pharmacology
Background:
- Salmonella typhi causes typhoid fever, a significant global health concern.
- Intracellular pathogens like S. typhi reside within host macrophages, complicating treatment.
- Assessing antibiotic efficacy against intracellular bacteria is crucial for effective therapy.
Purpose of the Study:
- To evaluate the in vitro efficacy of cefotaxime and ceftriaxone against Salmonella typhi within human macrophages.
- To compare the intracellular and extracellular antibacterial effects of these two cephalosporin antibiotics.
Main Methods:
- Human monocyte-derived macrophages were cultured and infected with S. typhi strains.
- Minimum Inhibitory Concentrations (MICs) of cefotaxime and ceftriaxone were determined.
- Antibiotics were added to cultures at 1x and 5x MIC values.
- Bacterial growth was assessed at various time points using nutrient agar cultures.
- Gentamicin was used to control for extracellular bacterial growth.
Main Results:
- Both cefotaxime and ceftriaxone exhibited significant in vitro antibacterial activity against S. typhi.
- No statistically significant difference was observed between the extracellular and intracellular effects of the antibiotics.
- Cefotaxime and ceftriaxone demonstrated high efficacy in eliminating extracellular S. typhi.
Conclusions:
- Cefotaxime and ceftriaxone are effective in killing intracellular Salmonella typhi in vitro.
- These antibiotics show promise for clinical use against susceptible intracellular pathogens like S. typhi.
