| Target Validation Information | |||||
|---|---|---|---|---|---|
| Target ID | T64410 | ||||
| Target Name | D-alanyl-D-alanine carboxypeptidase | ||||
| Target Type | Successful |
||||
| Drug Potency against Target | Ceftobiprole | Drug Info | MIC50 = 0.06 ug/ml | [552333] | |
| Ceftriaxone | Drug Info | MIC50 = 0.06 ug/ml | [552333] | ||
| Cefalotin | Drug Info | IC50 = 1000000 nM | [552218] | ||
| Cefotaxime | Drug Info | MIC50 = 0.015 ug/ml | [552333] | ||
| Action against Disease Model | Cefotaxime | The antimicrobial activities of cefixime, cefpodoxime, and ceftibuten were determined with 18 ampicillin-susceptible (Amps), 13 ampicillin-resistant beta-lactamase-producing (AmprBLP), and 7 ampicillin-resistant non-beta-lactamase-producing (AmprNBLP) strains of Haemophilus influenzae. An effect of inocul uM density on apparent MIC, the bactericidal activity of these agents,and the targets of the three cephems were determined. The MICs of cefixime, cefpodoxime, and ceftibuten for 90% of the Amps and AmprBLP isolates were 0.04, 0.08, and 0.08 microgram/ml, respectively. In contrast, the MICs for 90% of the AmprNBLP strains were 0.96, 1.92, and 7.68 micrograms/ml. No significant inocul uM effect was observed for any group of strains comparing inocula of 10(3) and 10(5) CFU, whereas only the AmprNBLP isolates showed a marked effect at an inocul uM of 10(6) CFU. Although bactericidal levels were achieved for the Amps and AmprBLP strains, tolerance to cefixime and ceftibuten was observed. The bactericidal activity for the AmprNBLP strains was limited, with cefixime showing the highest activity of the three cephems. Penicillin-binding proteins 2, 4, and 5 revealedhigh affinity, with 50% inhibitory concentration levels below the MIC for all three cephems, suggesting that these are important targets of these agents in H. influenzae. We conclude that the cephemsare highly active in vitro against Amps and AmprBLP strains of H. influenzae, but less so against AmprNBLP isolates. | [553120] | Drug Info | |
| References | |||||
| Ref 553120 | In vitro activities and targets of three cephem antibiotics against Haemophilus influenzae. Antimicrob Agents Chemother. 1989 Nov;33(11):1878-82. | ||||
| Ref 552333 | Novel antibacterial agents for the treatment of serious Gram-positive infections. Expert Opin Investig Drugs. 2003 Mar;12(3):379-99. | ||||
| Ref 552333 | Novel antibacterial agents for the treatment of serious Gram-positive infections. Expert Opin Investig Drugs. 2003 Mar;12(3):379-99. | ||||
| Ref 552218 | The cysteine-rich protein A from Helicobacter pylori is a beta-lactamase. J Biol Chem. 2000 Jun 9;275(23):17693-9. | ||||
| Ref 552333 | Novel antibacterial agents for the treatment of serious Gram-positive infections. Expert Opin Investig Drugs. 2003 Mar;12(3):379-99. | ||||
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