BACKGROUND: Carbapenem-resistant Enterobacterales species and multidrug-resistant Pseudomonas aeruginosa are global health threats. Cefepime-taniborbactam is an investigational ß-lactam and ß-lactamase inhibitor combination with activity against Enterobacterales species and P. aeruginosa expressing serine and metallo-ß-lactamases.
METHODS: In this phase 3, double-blind, randomized trial, we assigned hospitalized adults with complicated urinary tract infection (UTI), including acute pyelonephritis, in a 2:1 ratio to receive intravenous cefepime-taniborbactam (2.5 g) or meropenem (1 g) every 8 hours for 7 days; this duration could be extended up to 14 days in case of bacteremia. The primary outcome was both microbiologic and clinical success (composite success) on trial days 19 to 23 in the microbiologic intention-to-treat (microITT) population (patients who had a qualifying gram-negative pathogen against which both study drugs were active). A prespecified superiority analysis of the primary outcome was performed after confirmation of noninferiority.
RESULTS: Of the 661 patients who underwent randomization, 436 (66.0%) were included in the microITT population. The mean age of the patients was 56.2 years, and 38.1% were 65 years of age or older. In the microITT population, 57.8% of the patients had complicated UTI, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success occurred in 207 of 293 patients (70.6%) in the cefepime-taniborbactam group and in 83 of 143 patients (58.0%) in the meropenem group. Cefepime-taniborbactam was superior to meropenem regarding the primary outcome (treatment difference, 12.6 percentage points; 95% confidence interval, 3.1 to 22.2; P = 0.009). Differences in treatment response were sustained at late follow-up (trial days 28 to 35), when cefepime-taniborbactam had higher composite success and clinical success. Adverse events occurred in 35.5% and 29.0% of patients in the cefepime-taniborbactam group and the meropenem group, respectively, with headache, diarrhea, constipation, hypertension, and nausea the most frequently reported; the frequency of serious adverse events was similar in the two groups.
CONCLUSIONS: Cefepime-taniborbactam was superior to meropenem for the treatment of complicated UTI that included acute pyelonephritis, with a safety profile similar to that of meropenem. (Funded by Venatorx Pharmaceuticals and others; CERTAIN-1 ClinicalTrials.gov number, NCT03840148.).
| Specialty Area | Score |
|---|---|
| Nephrology | |
| Hospital Doctor/Hospitalists | |
| Internal Medicine | |
| Infectious Disease |
A useful article about a promising antibiotic for treating complicated UTI and pyelonephritis due to antibiotic-resistant gram-negative bacteria.
New antibiotic development is a key issue in the fight against multidrug-resistant bacteria. Although the promising combination of molecules evaluated in this trial (cefepime/taniborbactam) is effective, I believe there is not enough evidence to recommend it over more available drugs, such as carbapenems. Also, this trial does not provide clinical evidence about the effectiveness of cefepime/taniborbactam against carbapenemase-producing bacteria in humans.
The clinical problem addressed is prevalent, important, and currently has a less than satisfactory solution. This study provides convincing and novel data of the superiority of cefepime-taniborbactem with quite tolerable safety.
It's always good to have alternatives for complicated urinary tract infections. We see a number of multi-drug resistant organisms in patients who have returned after extended stays abroad. Cost and approval for hospital formularies, however, remain prime considerations for implementation.
It is clear that new drugs for cUTI are urgently needed. The results of this study provide hope for a new effective treatment option. I would be very interested in the results of a study that is not a head-to-head comparison with carbapenem, but shows which percentage of patients with refractory cUTI respond to this new drug combination.
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