In Vitro and In Vivo Activity of Tebipenem Against ESBL-Producing E. coli

Visanu Thamlikitkul MD*, Narisorn Lorchirachoonkul MD*, Surapee Tiengrim MSc**

Affiliation : * Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand ** Faculty of Medical Technology, Mahidol University, Bangkok, Thailand

Objective : To determine in vitro and in vivo activity of tebipenem against ESBL-producing E. coli. Material and Method: Minimum inhibitory concentration (MIC) of tebipenem against 100 clinical isolates of ESBL-producing E. coli was performed by broth micro-dilution technique. Blood and urine samples from 10 healthy male subjects before and after receiving 300 mg of tebipenem pivoxil 3 times a day for 2 consecutive days were determined for inhibitory and bactericidal titers against a clinical urinary isolate of ESBL-producing E. coli by disk diffusion method and broth micro- dilution method.
Results : MIC50 and MIC90 of tebipenem against ESBL-producing E. coli were both ≤0.06 mg/L with MIC range from ≤0.06 to 0.25 mg/L. The inhibition zones were observed around the disks inoculated with serum samples and urine samples collected from all study subjects after receiving tebipenem pivoxil for at least 1 hour and 5 hours, respectively. The inhibitory titer of 1:160 and bactericidal titer of 1:160 of serum samples were observed for at least one hour after ingestion of tebipenem pivoxil. Inhibitory titer of ≥1:640 and bactericidal titer of ≥1:640 of urine samples were observed after at least 14 hours after ingestion of tebipenem pivoxil. No subjects experienced side effects related to receiving tebipenem pivoxil.
Conclusion : Tebipenem is very active against ESBL-producing E. coli. Oral administration of tebipenem pivoxil 300 mg 3 times a day for two days was well tolerated, safe and induced high inhibitory and bactericidal activity in serum and urine. Tebipenem pivoxil could be an oral agent for effective therapy of ESBL-producing E. coli infections.

Keywords : Tebipenem, ESBL-producing E. coli, In vitro activity, In vivo activity

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