Research background and purpose
Complicated urinary tract infection refers to the presence of acquired infection at the same time as the occurrence of urinary tract infection, or the failure of urinary tract infection treatment caused by structural and functional abnormalities such as bladder and ureter, which is likely to cause progressive decline in renal function due to repeated recurrence, which requires great attention. Increasingly, such patients are hospitalized and treated with intravenous antibiotics, with limited oral regimens. Antibiotic resistance is on the rise worldwide, especially in the common Gram-negative pathogens that cause complicated urinary tract infections and acute pyelonephritis. Oral antibiotics that are effective against related pathogens are urgently needed.
Tebipenem Pivoxil Hydrobromide is an oral bioavailable carbapenem antibiotic that is active against urinary tract pathogenic Enterobacter, including ultra-broad-spectrum β-lactamase and fluoroquinolone-resistant strains. This International Phase 3 trial (ADAPT-PO) aims to evaluate the efficacy of oral Tebipenem Pivoxil Hydrobromide with intravenous ertapenem in hospitalized patients with complicated urinary tract infections or acute pyelonephritis.
Research methodology
In this international, double-blind, double-mock trial, patients were randomized on a 1:1 ratio to oral Tebipenem Pivoxil Hydrobromide (600 mg/8 h) or intravenous ertapenem (1 g/24 h) for 7 to 10 days (up to 14 days in patients with bacteremia). The primary efficacy endpoint was the overall response (a combination of clinical cure and microbial response) at the time of the cure test (TOC) visit (day 19, ±2-day window) in a microbiology-intended population. The non-inferiority cut-off was 12.5%.
Research results
A total of 1372 hospitalized adult patients were included, of which 868 (63.3%) were included in the microbiological intended treatment population (50.8% of patients had complicated urinary tract infections and 49.2% of patients had pyelonephritis).
efficacy
At THE TOC visit, the overall response rate of oral Tebipenem Pivoxil Hydrobromide was no less than that of intravenous ertapenem (58.8% and 61.6%, respectively; The weighted difference between the two sets is −3.3%; 95% confidence interval (CI), -9.7 to 3.2]. Its lower 95% CI limit of 9.7% is less than the non-inferiority cut-off value of 12.5%, so non-inferiority can be confirmed. At end-of-treatment (EOT) visits, the overall response rate in the Tebipenem Pivoxil Hydrobromide group was 97.3 percent and in the Extendem group 94.5 percent. At the TOC visit, the clinical cure rate in the Tebipenem Pivoxil Hydrobromide group was 93.1% and the clinical cure rate in the Ertapenem group was 93.6% (weight difference, –0.6%); 95% CI, -4.0 to 2.8) (Table 1).
Table 1 Evaluation of efficacy of two sets of trials (number percentage shown)
At the TOC visit, similar microbiological responses were observed in the enterobacter pathogens in both treatment groups, and the TOC response rates of E. coli (a common pathogen of urinary tract infections) in both treatment groups were also similar (62.7% in the Tebipenem Pivoxil Hydrobromide group and 65.2% in the Ertapenem group).
security
The Tebipenem Pivoxil Hydrobromide and Otapenem groups had 1 case (0.1%) and 8 cases (1.2%) of adverse events (AE) of premature discontinuation of the test drug in the Tebipenem Pivoxil Hydrobromide and otapenem groups, respectively. Nine (1.3%) and 12 (1.7%) patients in both groups had at least one serious adverse event (SAE) (Table 2). The overall incidence of AE in both groups was 25.7% and 25.6%, respectively, with more than 1% of patients reporting AE as diarrhea, headache, and nausea, and most AE being mild or moderate in severity and non-therapeutic limitation.
Table 2 Incidence of adverse reactions during the trial period
conclusion
Oral Tebipenem Pivoxil Hydrobromide is no less effective than intravenous ertapenem in patients with complicated urinary tract infection or acute pyelonephritis and has a similar safety profile.
Bibliography:
1. Meng Xianfeng,Zhang Zhe. Research progress in the treatment of complicated urinary tract infections in traditional Chinese medicine[J].Electronic Journal of Cardiovascular Diseases in Integrated Traditional Chinese and Western Medicine,2019,7(33):10+19.
2. Eckburg PB, Muir L, Critchley IA, et al. Oral Tebipenem Pivoxil Hydrobromide in Complicated Urinary Tract Infection. N Engl J Med. 2022 Apr 7;386(14):1327-1338.