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Antimicrobial activity of U-76,252 (CS-807), a new orally administered cephalosporin ester, including recommendations
Abstract:
U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807), was tested against 4,742 fresh clinical isolates from four large medical centers. U-76,253A was very active against nearly all species of Enterobacteriaceae (87.7% inhibited at less than or equal to 4.0 micrograms/ml). Staphylococcus spp., and the streptococci. The U-76,253A spectrum was superior to the comparison orally administered cephalosporins (cephalexin, cephradine, cefaclor). Pseudomonas spp., Acinetobacter spp., and the enterococci were resistant to U-76,253A and the other tested drugs. Broth microdilution MIC quality control (QC) limits were established for U-76,253A in a multilaboratory investigation using a minimum of 125 MIC determinations per organism. The following MIC QC ranges were recommended; Escherichia coli (ATCC 25922) = 0.25-1.0 micrograms/ml, Staphylococcus aureus (ATCC 29213) = 2.0-4.0 micrograms/ml and Pseudomonas aeruginosa (ATCC 27853) = greater than 32 micrograms/ml.
Insights
The active metabolite U-76,253A, derived from cephalosporin ester U-76,252, demonstrates broad activity against Enterobacteriaceae, Staphylococcus, and streptococci. This new antibiotic shows promise, outperforming existing oral cephalosporins in vitro.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- U-76,253A is the active metabolite of the novel cephalosporin ester U-76,252 (CS-807).
- Evaluating the in vitro activity of new antimicrobial agents is crucial for combating bacterial infections.
Purpose of the Study:
- To assess the in vitro antimicrobial activity of U-76,253A against a large panel of recent clinical isolates.
- To compare the spectrum of activity of U-76,253A with established oral cephalosporins.
- To establish quality control (QC) guidelines for U-76,253A susceptibility testing.
Main Methods:
- Broth microdilution method was employed to determine the minimum inhibitory concentrations (MICs).
- Testing was performed on 4,742 fresh clinical isolates from four major medical centers.
- Standardized QC procedures were followed, including multilaboratory investigations.
Main Results:
- U-76,253A exhibited high activity against most Enterobacteriaceae species, with 87.7% inhibited at ≤4.0 µg/ml.
- The compound was also active against Staphylococcus spp. and streptococci.
- Pseudomonas spp., Acinetobacter spp., and enterococci demonstrated resistance to U-76,253A, similar to control drugs.
Conclusions:
- U-76,253A possesses a potent in vitro spectrum of activity, particularly against Gram-negative Enterobacteriaceae and Gram-positive cocci.
- Its spectrum surpasses that of currently available oral cephalosporins, suggesting potential clinical utility.
- Established MIC QC ranges for key organisms (E. coli, S. aureus, P. aeruginosa) will facilitate reliable susceptibility testing.