Pharmacotherapy. 2021 Aug 9. doi: 10.1002/phar.2614. Online ahead of print.
Tebipenem pivoxil hydrobromide is a novel orally bioavailable prodrug of tebipenem, a carbapenem antimicrobial, that binds to penicillin binding proteins, inhibiting the synthesis of the bacterial cell wall. This results in weakening of peptidoglycan, leading to lysis of bacterial cells. Tebipenem displays a broad spectrum of activity against anaerobic, gram-positive, and gram-negative pathogens, including extended-spectrum β-lactamase producing Enterobacterales. In a large phase 3 clinical trial (ADAPT-PO), oral tebipenem pivoxil hydrobromide 600 mg every 8 hours was shown to be non-inferior to intravenous ertapenem 1 g every 24 hours. Overall response at test of cure was 58.8% [264/449] in the tebipenem pivoxil hydrobromide group compared to 61.6% [258/419] in the ertapenem group for the treatment of complicated urinary tract infections, including acute pyelonephritis. At the test of cure, clinical cure rates were 93.1% and 93.6% and microbiological eradication was 59.5% and 63.5% with tebipenem pivoxil hydrobromide and ertapenem, respectively. The most common adverse reactions associated with tebipenem pivoxil hydrobromide are diarrhea, headache, and nausea. As with other carbapenems, tebipenem pivoxil hydrobromide is expected to have the potential to decrease the seizure threshold and will likely require renal dosage adjustment for patients with altered renal function due to high renal clearance. If approved in the United States, tebipenem pivoxil hydrobromide can serve as a potential oral antimicrobial option to decrease hospital length of stay and prevent hospital admissions due to resistant pathogens.