Antibiotic Combo Approved for Multidrug-Resistant UTIs

The FDA approved intravenous cefepime and zidebactam (Zaynich) for complicated urinary tract infections (UTIs), including pyelonephritis, caused by susceptible gram-negative bacteria in adults, Wockhardt announced.

The novel antibiotic pairs a cephalosporin (cefepime) with a non-beta-lactam antibacterial and beta-lactamase inhibitor (zidebactam) to target a wide range of multidrug-resistant and extensively drug-resistant gram-negative bacteria, including Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter cloacae complex, and Pseudomonas aeruginosa.

FDA based its decision on the phase III ENHANCE-1 trial, which showed the combination to be effective compared with meropenem (89% vs 68.4%) at achieving clinical cure and microbiological response among patients hospitalized with complicated UTIs or acute pyelonephritis.

Complicated UTIs include any occurring in male, pregnant, or immunocompromised patients, as well as infections that involve the kidneys or are linked to fevers, stones, urinary obstruction, catheters, or sepsis. Complicated UTIs are associated with significant morbidity and mortality and are increasingly caused by antimicrobial-resistant bacteria, including multidrug-resistant bacteria. In the U.S., these infections lead to more than 620,000 hospital admissions annually.

“Multidrug-resistant bacterial infections are a substantial burden for patients and the healthcare system, as patients with these infections typically require longer, more intensive care, and are at increased risk of life-threatening complications,” Keith Kaye, MD, MPH, of Rutgers Robert Wood Johnson Medical School in New Jersey, said in the drugmaker’s press release.

“There is an ongoing need for new antibiotics to combat these drug-resistant pathogens, and we are pleased that this approval means patients will soon have an exciting unique option that is urgently needed in the U.S. and worldwide,” Kaye added.

The most common adverse events (at least 2%) in patients treated with cefepime-zidebactam were diarrhea, hypertension, headache, and hypokalemia. Contraindications noted in the prescribing information include a patient history of serious hypersensitivity to cefepime, zidebactam, or other beta-lactam antibacterial drugs. The label also includes warnings for Clostridioides difficile infections and neurotoxicity in geriatric patients or those with renal impairment.

The combination’s recommended dosage is 3 g (cefepime 2 g, zidebactam 1 g) every 8 hours via IV infusion for 7 to 10 days in adults who have an estimated glomerular filtration rate (eGFR) of at least 60 mL/min. Dosages can be adjusted for patients with a lower eGFR.