Pharmacodynamic Studies Of Ceftiofur

This paper studied the pharmacodynamics of Ceftiofur and other B-lactam (Ceftriaxone and Ampicillin) antibiotics . The content of the studies included four parts: the minimal inhibitory concentrations (MICs) and minimal bactericidal (MBCs) to many clinical and standard strains, the killing-curves to four standard strains (E.coli, S.pullorum,S.aureus, S.suis),the post-antibiotic effects (PAEs) to four standard strains (E.coli, S.pullorum, S.aureus, S.suis), the therapeutic experiment (prevention and cure) in vivo using S.pullorum infection models.The results of antimicrobial susceptibility in vitro showed that Ceftiofur was a broad-spectrum Cephalosporin with potent activity against all kinds of clinical and standard strains; To the standard strains, the MICs was in the range of 0.00625-0.8 g/ml, and to the clinical strains, the MIC50 (the MIC of antibiomic that inhibits 50% of strains tested) and MIC% (the MIC of antibiomic that inhibits 90% of strains tested) were low, and respectively, the MIC50 and MIC90 were in the range of 0.24-4.2 g/ml, 0.6-11 g/ml; Which also indicated that Ceftiofur had better activity against gram-negative bacteria (G~ bacteria) and lower activity against gram-positive bacteria (G+ bacteria) than Ampicillin; In addition, the antimicrobial susceptibility showed that all kinds of bacteria produced high resistance to Ampicillin, however, Ceftiofur had good activity against these clinical strains. The results of killing-curves to four standard strains indicated that Ceftiofur and other B-lactam antibiotics (Ceftriaxone and Ampicillin) had higher killing rates; Thereinto, Ampicillin (8MIC, 5MIC, 2MIC) had higher killing rates to S. aureus and S. suis than Ceftiofur; on the reverse, Ceftiofur (8MIC, 5MIC, 2MIC) had higher killing rates to E. coli and S. pullorum than Ampicillin. Moreover, Ceftiofur and Ceftriaxone (8MIC, 5MIC, 2MIC) had the similar killing rates and killing-curves to four standard strains (P>0.05). Besides, the killing rates of Ceftiofur, Ceftriaxone, and Ampicillin weren't positively correlative with the drug concentrations (8MIC,5MIC,2MIC) (P>0.05), as well as that they were antibiotics that didnt depend on drug concentration. In in-vivo PAE study, the results showed that, to S. aureus and S. suis, the PAEs of ceftiofur and other B-lactam antibiotics (Ceftriaxone and Ampicillin) were positively correlative with the drug concentrations (8MIC, 5MIC, 2MIC) (P<0.05); Obviously, to S. aureus and S. suis, Ampicillin had a longer PAEs than Ceftiofur (P<0.05), approximately, which was in the range of 0.4-0.7 hour; But, to E. coli and S. pullorum, all the drugs (including Ceftiofur) had short or negative PAE (<0.3h <0h), which indicated that the PAEs of all the drugs weren't positively correlative with the drug concentrations(P>0.05).In in-vivo therapeutic experiment using S. pullorum infection models, the therapeutic effects of Ceftiofur were better than Ceftriaxone and Ampicillin. Thereinto, the high dose (0.2mg) of Ceftiofur had the similar therapeutic effects with the middle dose of Ceftiofur (0.1mg) (P>0.05), respectively, their healing rate was 86.7%>83.3%, and their effective rate was 93.3%, 90%; Otherwise, it's low dose had bad therapeutic effects than the middle dose, their healing rate was 83.3%, 53.3%, and their effective rate was 90% , 66.7%, respectively; But, to Ceftriaxone and Ampicillin, the therapeutic effects of Ceftiofur (the middle dose) were obvious (P<0.05 or P<0.01); According to the result of prevention experiments in-vivo, to Ceftriaxone and Ampicillin, the middle dose of Ceftiofur could effectively prevent the disease(the effective rate was 80.0%, 63.3%, 33.3%). So, the prevention and cure experiment in vivo showed that Ceftiofur had potent advantage as a animal drug, and the middle dose (0.1 mg) of ceftiofur could prevent and cure the disease.