medwireNews: Patients with complicated urinary tract infections (UTI) have superior microbiologic and clinical success rates with cefepime–taniborbactam than with meropenem treatment, suggest findings from the CERTAIN-1 study.
In this randomized phase 3 clinical trial, 70.6% of 293 patients treated with the β-lactam and β-lactamase inhibitor cefepime–taniborbactam for a week achieved a composite of microbiologic and clinical success on days 19 to 23, compared with 58.0% of 143 patients who instead received the carbapenem antibiotic meropenem.
Microbiologic success was defined as a reduction in all gram-negative bacterial pathogens to below 103 CFU/mL. At baseline, the patients had gram-negative bacterial pathogens against which both study drugs were active at this level or above. Clinical success was defined as symptomatic resolution of all core signs and symptoms to pre-infection levels without the use of additional antibacterial agents for complicated UTI.
A treatment difference of 12.6 percentage points was observed for this primary efficacy outcome, indicating “superiority of cefepime–taniborbactam over meropenem,” Florian Wagenlehner (Justus Liebig University, Giessen, Germany) and team report in The New England Journal of Medicine.
Among the study participants, 57.8% had complicated UTI and 42.2% had acute pyelonephritis specifically. Bacteremia was present in 13.1% of patients. The average age of the patients was 56.2 years and 38.1% were 65 years of age or older.
Most of the pathogens identified at baseline in both groups belonged to the Enterobacterales species (96%), with Escherichia coli being the most common (69%), followed by Klebsiella pneumoniae (14%), Proteus mirabilis (5%), and Enterobacter cloacae complex (4%). Pseudomonas aeruginosa accounted for 4% of the baseline isolates.
Baseline pathogens that were resistant to cefepime, pathogens producing extended-spectrum β-lactamase, and multidrug-resistant pathogens were present in a respective 22.0%, 26.6%, and 35.6% of patients, overall.
Intravenous cefepime–taniborbactam (cefepime 2.0 g and taniborbactam 0.5 g) was administered every 8 hours over a 2-hour period, while meropenem 1.0 g was given every 8 hours over a 30-minute period, both for 7 days. Treatment could be extended up to 14 days or bacteremia. Both groups received treatment for a median of 7 days.
The researchers note that the difference in response between the two treatment groups was sustained at days 28 to 35, at which point rates for both composite success and clinical success were higher with cefepime–taniborbactam than meropenem, at 63.8% versus 51.7% and 70.6% versus 62.9%, respectively.
These findings are particularly significant as the patients “had pathogens that were susceptible to both cefepime–taniborbactam and meropenem,” say the investigators.
They report that “[r]esults consistent with the primary findings were observed across subgroups of patients, including those with potentially more severe disease (bacteremia or [systemic inflammatory response syndrome]) and across baseline pathogens and antimicrobial resistance categories.”
Adverse events occurred in 35.5% of patients receiving cefepime-taniborbactam and 29.0% of those receiving meropenem, with the most common in the cefepime-taniborbactam group being headache (6.1 vs 3.7%), diarrhea (4.1 vs 2.3%), constipation (3.2 vs 1.4), hypertension (2.3 vs 0.9%), and nausea (2.0 vs 0.9%). The frequency of serious adverse events was similar, at 2.0% with cefepime-taniborbactam and 1.8% with meropenem.
“Most adverse events in both groups were mild or moderate in severity and did not result in the discontinuation of treatment,” say Wagenlehner et al.
They conclude that “cefepime–taniborbactam was shown to be a potential treatment option for patients with complicated UTI and acute pyelonephritis caused by Enterobacterales species and P. aeruginosa, including antimicrobial-resistant strains.”
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