A comparative study on the inhibitory actions of chloramphenicol, thiamphenicol and some fluorinated derivatives

Abstract

Chloramphenicol, thiamphenicol and three fluorinated derivatives, Sch 24893, Sch 25298 and Sch 25393, were studied with respect to inhibition of the growth of selected bacterial strains and cell-free translation systems. Thiamphenicol was the least potent inhibitor in the former experiments, but behaved similarly to chloramphenicol and Sch 25298 in the latter, thereby displaying selective inhibition of prokaryotic protein synthesis. Thiamphenicol and Sch 25298 were shown to be like chloramphenicol in inhibiting peptidyl transferase activity specifically on 70 S ribosomes, but the antibiotics bound to their common ribosomal-receptor site with different efficiencies in the order chloramphenicol greater than thiamphenicol greater than Sch 25298. Selected bacterial strains highly resistant to chloramphenicol and thiamphenicol because of chloramphenicol acetyltransferase production were, in contrast, highly sensitive to inhibition by the fluorinated antibiotics. Thus Sch 24893, Sch 25298 and Sch 25393 may have important uses in veterinary and clinical medicine.

Evaluation of Antibiotic Susceptibilities of Ehrlichia canis , Ehrlichia chaffeensis , and Anaplasma phagocytophilum by Real-Time PCR

“…In practice, chloramphenicol is not widely used because of hematological side effects and inconsistent activity (1,11,16,17,19,21). Both chloramphenicol and thiamphenicol inhibit protein synthesis by decreasing peptidyl transferase activity of the 70S ribosome subunit, but chloramphenicol binds to the target site with higher affinity and dramatically decreases polynuclear phagocytic function (10). Thiamphenicol would have the advantage of being less toxic (43), but further clinical data are needed to define the usefulness of this drug.…”

Inactivation of Chloramphenicol and Florfenicol by a Novel Chloramphenicol Hydrolase

“…Otherwise, many drug exporters mediate Cm resistance in a bacterial system by specifically or nonspecifically driving out the antibiotic (2,22,25). Of note, the known CAT is unable to inactivate Ff, due to the specific fluoro substitution at C 3 (7,31). Only a small number of the Cm resistance genes identified to date mediate cross-resistance to Ff; these mainly encode drug efflux pumps.…”

Pharmacokinetics of Florfenicol in Healthy Pigs and in Pigs Experimentally Infected with Actinobacillus pleuropneumoniae

“…Florfenicol has a mechanism for inhibiting the protein synthesis of susceptible bacteria by combining simultaneously with the 50S and 70S subunits in the ribosome to abolish the activity of peptidyl transferase (5,7). Florfenicol has been shown to not only circumvent the bacterial acetyltransferase-mediated drug resistance but also to ameliorate the risk of inducing drug-related aplastic anemia in humans (9,11).…”