Imipenem

Preparation Method

Susceptibilities of Y. pestis strains were determined by the broth microdilution method according to CLSI M45-A2

Reaction Conditions

0.04-2mg/L imipenem in 35°C

Applications

The MICs for the Y. pestis strains with imipenem ranged from a low of 0.12 mg/liter to a high of 1.0 mg/liter，the higher is 0.5 mg/liter

Cell experiment

THP-1 cells

Preparation Method

THP-1 cells were seeded into 24-well plates, differentiated for 24 h and infected with M. abscessus CIP104536. Imipenem (8 and 32 mg/L) or amoxicillin alone or in combination with relebactam (16 mg/L) or avibactam (16 mg/L) were added to each well. Rifabutin was also studied in combination with imipenem (8 mg/L), imipenem/relebactam or imipenem/avibactam. Imipenem was added every 24 h.

Reaction Conditions

Imipenem (8 and 32 mg/L) was added every 24 h.

Applications

Combination of relebactam with β-lactams led to >128- and 2-fold decreases in the MICs of amoxicillin and imipenem (from 8 to 4 mg/L). In vitro, M. abscessus was not killed by the imipenem/relebactam combination. In contrast, relebactam increased the intracellular activity of imipenem, leading to 88% killing.

Animal models

Female C57BL/6 mice (6-8 weeks old, 20-25 g body weight)

Preparation Method

Mice were randomly divided into four groups: the sham-operated mice as the control group, CLP-induced sepsis mice, CLP-induced sepsis mice treated with the low dose of imipenem (25 mg/kg), CLP-induced sepsis mice treated with the high dose of imipenem (125 mg/kg). Imipenem was injected one hour after sepsis induction, repeating the injection every 24 h up to 72 h.

Dosage form

25-200 mg/kg imipenem, repeating the injection every 24 h up to 72 h.

Applications

Sepsis mice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. Significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem. Liver tissue pathology of mice indicated little tissue destruction in the sepsis mice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate.

References:

[1]. Heine HS, Louie A, et,al. Evaluation of imipenem for prophylaxis and therapy of Yersinia pestis delivered by aerosol in a mouse model of pneumonic plague. Antimicrob Agents Chemother. 2014 Jun;58(6):3276-84. doi: 10.1128/AAC.02420-14. Epub 2014 Mar 31. PMID: 24687492; PMCID: PMC4068467.

[2]. Le Run E, Atze H, et,al. Impact of relebactam-mediated inhibition of Mycobacterium abscessus BlaMab β-lactamase on the in vitro and intracellular efficacy of imipenem. J Antimicrob Chemother. 2020 Feb 1;75(2):379-383. doi: 10.1093/jac/dkz433. PMID: 31637424.

[3]. Khosrojerdi A, Soudi S, et,al. Imipenem alters systemic and liver inflammatory responses in CLP- induced sepsis mice in a dose-dependent manner. Int Immunopharmacol. 2021 Apr;93:107421. doi: 10.1016/j.intimp.2021.107421. Epub 2021 Feb 4. PMID: 33548581.