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Comparative activities of cefotiam and cefazolin against urinary tract infections with Proteus mirabilis in mice
Abstract:
The therapeutic effect of cefotiam on experimental urinary tract infections with Proteus mirabilis IFO 3849 in mice was compared with that of cefazolin. The minimal inhibitory concentrations of cefotiam and cefazolin against the test organism were 1.56 and 25 micrograms/ml, respectively. Beginning 3 days after infection, various doses of each cephalosporin were given subcutaneously twice a day for 5 days. Doses of 100 mg of cefotiam per kg or more sterilized the urine within 3 days and effected a marked reduction or complete eradication of bacteria in the bladder walls and kidneys of mice sacrificed the day after treatment was terminated. A dose of cefazolin greater than 800 mg/kg was required for equivalent therapeutic results. Clearance of bacteria from urinary tract organs was as rapid or more rapid with 50-mg/kg doses of cefotiam as with 200-mg/kg doses of cefazolin. Much more rapid clearance was attained with 200-mg/kg doses of cefotiam. The concentrations of cefotiam attained in plasma, kidney, and urine were lower than the cefazolin levels achieved at an equivalent dose. The superiority of cefotiam over cefazolin in treatment of experimental urinary tract infections appears to be due to its greater activity against the test organism.
Insights
Cefotiam demonstrated superior efficacy in treating experimental urinary tract infections caused by Proteus mirabilis in mice compared to cefazolin. Cefotiam achieved rapid bacterial eradication at lower doses, highlighting its enhanced antimicrobial activity.
Area of Science:
- Microbiology
- Pharmacology
- Infectious Diseases
Background:
- Urinary tract infections (UTIs) are common bacterial infections.
- Proteus mirabilis is a significant causative agent of UTIs, often associated with complications.
- Evaluating novel or existing antibiotics for UTI treatment is crucial.
Purpose of the Study:
- To compare the therapeutic efficacy of cefotiam and cefazolin in a murine model of Proteus mirabilis UTI.
- To assess the dose-response relationship and bacterial clearance rates for both antibiotics.
Main Methods:
- Experimental UTI was induced in mice using Proteus mirabilis IFO 3849.
- Mice were treated with varying subcutaneous doses of cefotiam or cefazolin twice daily for 5 days.
- Bacterial loads in urine, bladder, and kidneys were quantified post-treatment.
Main Results:
- Cefotiam exhibited significantly lower minimum inhibitory concentrations (MICs) against Proteus mirabilis than cefazolin (1.56 vs. 25 µg/ml).
- Doses of 100 mg/kg/day of cefotiam sterilized urine within 3 days and eradicated bacteria from urinary organs.
- Equivalent therapeutic effects with cefazolin required doses exceeding 800 mg/kg/day.
- Cefotiam demonstrated faster bacterial clearance from urinary tract organs, even at lower doses compared to cefazolin.
Conclusions:
- Cefotiam is therapeutically superior to cefazolin for experimental Proteus mirabilis UTIs in mice.
- The enhanced efficacy of cefotiam is attributed to its greater in vitro activity against the tested organism.
- These findings support cefotiam as a potentially more effective treatment option for specific UTIs.