Pharmacokinetics of tebipenem pivoxil used in children suffering from shigellosis: a pilot study in Bangladesh

Abstract

With increasing antibiotic resistance in gram-negative bacteria, including those causing Shigellosis, evidence of safety and pharmacokinetics data on new oral antibiotics is crucial. We aimed to investigate the safety and pharmacokinetic properties of an oral carbapenem, tebipenem pivoxil, along with it’s ability to produce desired results in childhood shigellosis. This randomized pilot clinical trial was conducted at Dhaka Hospital, icddr,b in 2022 between May and September. Thirty suspected shigellosis cases aged 24–59 months were randomized across two treatment groups equally: tebipenem pivoxil and azithromycin. Pharmacokinetics of tebipenem was assessed among fifteen children who received tebipenem pivoxil using Noncompartmental analysis (NCA). Clinical (absence of fever, abdominal pain/tenderness, diarrhoea, blood in stool, or death before Day-3) and microbiological (absence of Shigella on Day-7 culture) success after the antibiotic interventions were also evaluated. Sociodemographic and clinical characteristics were comparable between the randomization arms. Twelve children, each in the azithromycin arm and tebipenem arm, were positive for Shigella by culture on enrolment. Cmax values of 5053.3, 2546.0, and 3759.2 ng/mL were observed for plasma tebipenem on Day-0, 1, and 2 respectively. Clinical success was observed among seven participants in each arm while two in the azithromycin arm and three in the tebipenem arm failed microbiologically. The tolerability and efficaciousness of tebipenem pivoxil appear to be comparable to azithromycin in treating childhood shigellosis in Bangladesh. We recommend a larger clinical trial to determine non-inferiority of tebipenem in regards to the current treatment guidelines.