tebipenem and Communicable-Diseases

Diarrhoea remains one of the leading causes of childhood mortality globally. Recent epidemiological studies conducted in low-middle income countries (LMICs) identified. Aiming to identify alternative antimicrobial chemicals with activity against antimicrobial resistant. We identified several known antimicrobial compound classes with antibacterial activity against. Our data highlight the emerging antimicrobial resistance crisis and shows that Tebipenem pivoxil (licenced for paediatric respiratory tract infections in Japan) should be accelerated into human trials and could be repurposed as an effective treatment for severe diarrhoea caused by MDR. Tres Cantos Open Lab Foundation (projects TC239 and TC246), the Bill and Melinda Gates Foundation (grant OPP1172483) and Wellcome (215515/Z/19/Z).

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Carbapenems; Child; Communicable Diseases; Diarrhea; Drug Repositioning; Humans; Mice; Shigella; Swine

Tebipenem pivoxil hydrobromide is a novel oral carbapenem prodrug of tebipenem, the active moiety. We assessed tebipenem steady-state pharmacokinetics in the skin and soft tissue in healthy subjects and infected patients with diabetes using in vivo microdialysis.. Six healthy subjects and six patients with an ongoing diabetic foot infection (DFI) received tebipenem pivoxil hydrobromide 600 mg orally every 8 h for three doses. A microdialysis probe was inserted in the thigh of healthy subjects or by the wound margin in patients. Plasma and dialysate samples were obtained immediately prior to the third dose and sampled over 8 h.. Tebipenem plasma protein binding (mean ± SD) was 50.2% ± 2.4% in healthy subjects and 53.5% ± 5.6% in infected patients. Mean ± SD tebipenem pharmacokinetic parameters in plasma for healthy subjects and infected patients were: maximum free concentration (fCmax), 3.74 ± 2.35 and 3.40 ± 2.86 mg/L, respectively; half-life, 0.88 ± 0.11 and 2.02 ± 1.32 h; fAUC0-8, 5.61 ± 1.64 and 10.01 ± 4.81 mg·h/L. Tebipenem tissue AUC0-8 was 5.99 ± 3.07 and 8.60 ± 2.88 mg·h/L for healthy subjects and patients, respectively. The interstitial concentration-time profile largely mirrored the free plasma profile within both populations, resulting in a penetration ratio of 107% in healthy subjects and 90% in infected patients.. Tebipenem demonstrated excellent distribution into skin and soft tissue of healthy subjects and patients with DFI following oral administration of 600 mg of tebipenem pivoxil hydrobromide.

Topics: Communicable Diseases; Diabetes Mellitus; Diabetic Foot; Healthy Volunteers; Humans; Microdialysis; Monobactams; Tissue Distribution