Comparison of antibacterial efficacy of domestic and branded tigecycline with in vitro Pharmacokinetics/Pharmacodynamics model / 中华临床感染病杂志

ABSTRACT

Objective:To compare the antibacterial activity of domestic and branded tigecycline with in vitro pharmacokinetics (PK)/pharmacodynamics (PD) model. Methods:The in vitro PK automatic simulation system PASS400 was used to simulate different doses of tigecycline administration regimen (100 mg, 1 time/d; 50 mg, 12 h/d; 100 mg, 12 h/d), and to observe domestic and imported tigecycline time sterilization curve and related pharmacodynamic parameters of the drug against the standard strain of Escherichia coli (ATCC25922), carbapenem-resistant Klebsiella pneumoniae (ATCC BAA-1706) and the clinical strain of Acinetobacter baumannii (AB-16703). The GraphPad Prism 7 statistical software was used to analyze the data. Results:Under the condition of simulating different doses of PK, domestic and original tigecycline had similar antibacterial effects, but both showed weak antibacterial effects. The time sterilization curves of the two were almost overlapped, and the maximum sterilization amount was less than 2 log. Within 24 h, the bacteria all recovered to the growth plateau. In the comparison of PD parameters, the original and domestic tigecycline (100 mg, 1 time/12 h) had the maximum bactericidal doses of (-1.101±0.147) lg CFU/mL and (-1.105±0.208) lg CFU/mL for Escherichia coli ATCC25922; the maximum bactericidal capacity for Klebsiella pneumoniae ATCC BAA-1706 was (-1.999±0.187) lg CFU/mL and (-1.865±0.066) lg CFU/mL; the maximum bactericidal capacity for Acinetobacter baumannii AB-16703 was (-0.240±0.209) lg CFU/mL and (-0.230±0.187) lg CFU/mL. Under different dosage regimens, the maximum sterilization amount against the three bacteria, the time required for the bacteria to regenerate to the initial amount, the 24 h bacterial reduction, and the difference between the area of the sterilization and recovery growth curve and the blank control curve were all not statistical significant between the two drugs ( P>0.05). Conclusion:Tigecycline cannot show good antibacterial activity under the conditions of simulating human drug metabolism in vitro. The original branded tigecycline and domestic tigecycline have similar in vitro PK/PD effects.