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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2023, Vol. 28 ›› Issue (9): 1027-1033.doi: 10.12092/j.issn.1009-2501.2023.09.008

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Evaluation of tegacycline regimens in treatment of gram-negative bacterial infections with Monte Carlo simulation

WU Yujie, ZHAO Chengcheng, XI Qing   

  1. Department of Pharmacy , General Hospital of Aviation, Beijing 100012, China
  • Received:2023-03-01 Revised:2023-05-17 Online:2023-09-26 Published:2023-09-25

Abstract:

AIM: To evaluate the dose regimens of tegacycline for treatment of hospital-acquired pneumonia, complex abdominal infection and complex skin and soft tissue infection caused by Gram-negative bacterial infections with Monte Carlo model. METHODS: The minimum inhibitory concentrations (MICs) of tegacycline against Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae were collected from the CHINET in 2018. The target probability (PTA) and cumulative response fraction (CFR) of different regimens were calculated using Monte Carlo simulation based on PK/PD theory of tegacycline. RESULTS: In the treatments of HAP caused by gram-negative bacteria, when MIC≤0.5 μg/mL, the PTA of 50 mg q12h was greater than 90%, and when MIC≥1 μg/mL, PTA and CFR of 100 mg q12h were both greater than 90%, When MIC≥2 μg/mL, 50 mg q12h, 75 mg q12h and 100 mg q12h doses of PTA were less than 90%. In the treatment of cIAI, when MIC≤0.5 μg/mL, PTA of 50 mg q12h reached the target value, and when MIC=1 μg/mL, PTA of 100 mg q12h was greater than 90%. For complex skin and soft tissue infection, when the MIC≤0.25 μg/mL, the PTA of 75 mg q12h and 100 mg q12h was greater than 90%, and the PTA of the three administration regimen was less than 90%, when the MIC≥0.5 μg/mL. CONCLUSION: The dose of 50 mg q12h is more suitable for the treatment of HAP, when MIC>0.5 μg/mL, tigecycline may need 100 mg q12h to obtain the best clinical efficacy in the treatment of cIAI. For cSSSI. when MIC≤0.25 μg/mL, tigecycline can be administered with 75 mg q12h and 100 mg q12h. For the three types of infections caused by Escherichia coli, the conventional dose of tigecycline may achieve clinical efficacy.

Key words: tegacycline, gram-negative bacteria, Monte Carlo simulation, pharmacodynamics/pharmacokinetics

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