1. In this randomized controlled trial, among hospitalized adults with a complicated urinary tract infection (UTI), cefepime-taniborbactam was superior to meropenem in achieving microbiologic and clinical resolution.
2. Cefepime-taniborbactam had a similar safety profile to meropenem with comparable rates of serious adverse events.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Complicated UTI, including acute pyelonephritis, accounts for a high number of hospitalizations. Emerging bacterial resistance to b-lactam antibiotics poses a challenge in treating these serious infections. Cefepime-taniborbactam, a combination of a fourth-generation cephalosporin and a potent novel b-lactamase inhibitor, has been shown pre-clinically to be active against multidrug-resistant Enterobacterales species and Pseudomonas aeruginosa, including strains resistant to meropenem and other b-lactam-b-lactamase inhibitor combinations. This study was a phase three trial comparing cefepime-taniborbactam against meropenem in treating complicated UTIs among hospitalized adults. In the microbiologic intention-to-treat (microITT) population with evidence of gram-negative infection susceptible to both drugs, cefepime-taniborbactam demonstrated a higher rate of composite microbiologic and clinical success than meropenem, both at early (days 19-23) and late (days 28-35) follow-ups. Both drugs had similar safety profiles, with headache, gastrointestinal symptoms, and hypertension being the most common. The stringent study design may not reflect clinical practice, with fixed duration of intravenous antibiotic therapy without oral stepdown and classifying asymptomatic bacteriuria as composite failure. Nevertheless, it demonstrated cefepime-taniborbactam as an additional treatment option for patients with complicated UTIs caused by resistant bacteria.
Click here to read the study in NEJM
In-Depth [randomized controlled trial]: The current study was a randomized controlled trial assessing the efficacy of cefepime-taniborbactam against meropenem in treating complicated UTIs. Adult hospitalized patients 18 years of age or older diagnosed with a complicated UTI or acute pyelonephritis were eligible for inclusion. Exclusion criteria included receipt of antibiotics for complicated UTI within 24 hours before randomization, meropenem-resistant infection, severe renal and hepatic impairment, renal abscess, and hypersensitivity to the study drugs. In total, 436 patients who were included in the microITT, who had a qualifying gram-negative species susceptible to study drugs, were randomized 2:1 to receive cefepime-taniborbactam (2g of cefepime and 0.5g taniborbactam) every eight hours or meropenem (1g) every eight hours for seven days. The primary efficacy outcome was a composite of microbiologic and clinical success on trial days 19 to 23. Microbiologic success was defined as a gram-negative bacteria count being reduced to <103 colony-forming units/mL. Clinical success was defined as resolving symptoms or returning to baseline with no need for additional antibiotic therapy. A total of 57.8% of the included patients had complicated UTIs, 42.2% had acute pyelonephritis, and 13.1% had bacteremia. Composite success was achieved in 70.6% of patients who received cefepime-taniborbactam and 58.0% of those who received meropenem (treatment difference, 12.6 percentage points; 95% Confidence Interval [CI], 3.1-2.2; p=0.009), demonstrating superiority of cefepime-taniborbactam. This superiority was demonstrated in the extended microITT population, which included pathogens resistant to at least on the study drugs, (treatment difference, 12.3 percentage points; 95% CI, 3.0-21.8). The rate of adverse events was 35.5% for cefepime-taniborbactam and 29.0% for meropenem. These results demonstrated the efficacy and safety of cefepime-taniborbactam as a therapy option for acute complicated UTI and pyelonephritis with resistant bacteria.
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