WASHINGTON — The new antibiotic cefiderocol was non-inferior to standard of care for patients with nosocomial pneumonia, a researcher said here.
A phase III non-inferiority trial found no significant difference in 14-day all-cause mortality among patients randomized to receive cefiderocol compared with those randomized to high-dose meropenem (12.4% vs 11.6%, respectively), reported Yuko Matsunaga, PhD, of Shionogi in Florham Park, New Jersey.
Secondary outcomes were similar, with no difference in clinical and microbiologic outcomes at test of cure 7 days after treatment, he reported at a late-breaking presentation at the IDWeek meeting, with joint sponsorship by the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, the Society for Healthcare Epidemiology of America (SHEA), and the HIV Medicine Association.
Cefiderocol is a new β-lactam antibiotic, a “very old class” of antibiotics that includes penicillin, James Hackworth, PhD, of Shionogi, told MedPage Today. But it acts differently than its siderophore cephalosporin brethren, as it appears to be able to get around β-lactam resistance through its mechanism of action. “[Cefiderocol] gets in [to the bacteria] more easily and once it’s in, it doesn’t get destroyed by the beta-lactamase,” he said.
Due to its chemical structure, cefiderocol only has activity against Gram-negative bacteria, which Hackworth said is not standard for β-lactams, but Gram-negative bacteria have “the biggest problem in terms of resistance.”
He added that cefiderocol for treatment of complicated urinary tract infections is scheduled to be reviewed at an FDA advisory committee meeting on Oct. 16, 2019, with a “hopeful initial approval” in November. The current trial in patients with nosocomial pneumonia would then be submitted under a separate supplemental new drug application, Hackworth added.
“It is interesting we have not only a novel type of antibiotic construct, but we also have a clinical trial showing this type of antibiotic can at least have a similar outcome to standard of care,” Andre Kalil, MD, of the University of Nebraska Medical Center in Omaha, told MedPage Today.
“Hopefully we can have a new medication to treat these patients [after the drug goes under FDA evaluation],” said Kalil, who was not involved in the study.
This APEKS-NP (Acinetobacter, Pseudomonas, Escherichia coli, Klebsiella, Stenotrophomonas-Nosocomial Pneumonia) trial randomized 300 patients — 152 of whom received 2 g of intravenous cefiderocol and 148 of whom received 2 g intravenous meropenem, both infused over 3 hours every 8 hours, plus linezolid. The margin of non-inferiority was 12.5%, the authors noted.
Participants were adult patients with hospital-acquired, ventilator-associated or healthcare-associated pneumonia with suspected Gram-negative bacterial infection in the lower respiratory tract. Clinical diagnostic criteria followed FDA and European Medicines Agency nosocomial pneumonia guidance, Matsunaga said. Patients were a mean age of about 65, two-thirds were from Europe and almost 70% were men. About 60% required mechanical ventilation.
About 84% of patients in both groups had documented Gram-negative infection, and the top four pathogens were Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and E. coli.
In addition to non-inferiority for 14-day all-cause mortality, cefiderocol was non-inferior to standard of care at the secondary endpoints of all-cause mortality at day 28 (21.0% vs 20.5%) or the end of study (26.8% vs 23.3%). Clinical cure rates at test of cure were also comparable between cefiderocol and control group (64.8% vs 66.7%, respectively), with higher clinical response rates in patients with healthcare-associated pneumonia versus patients with ventilator-associated or hospital-acquired pneumonia.
Examining safety, treatment-related adverse events (TRAEs) were also similar, with about 87% of patients reporting TRAEs, and Matsunaga noted there were no issues specific to the cefiderocol group.
But Kalil noted that “safety is something that you can never fully see in one clinical trial, so we will have to keep watching carefully when this drug comes to standard of care.”
Matsunaga concluded that the study showed that cefiderocol can be a treatment option for patients at risk of hospital-acquired pneumonia and ventilator-associated pneumonia caused by multi-drug resistant Gram-negative pathogens.
Co-authors disclosed support from Shionogi and Merck.
Source: MedicalNewsToday.com
