New Treatment Affective Against Drug-resistant Bacteria

Researchers have found a new drug to treat patients with infections caused by antibiotic-resistant Gram-negative uropathogens. 

The phase 2, multi-center, double-blind, parallel-group non-inferiority trial included adults (age ≥ 18 years) at 67 hospitals in 15 countries with a clinical diagnosis of complicated urinary tract infection with or without pyelonephritis or acute uncomplicated pyelonephritis. Patients were randomly assigned to intravenously receive 2 g of the new drug, cefiderocol, or 1 g of imipenem-cilastatin for one hour three times a day, every eight hours, for one to two weeks. The final analysis included 371 patients (cefiderocol, n = 252; imipenem-cilastatin, n = 119). 

After treatment, 183 (73%) of the cefiderocol patients and 65 (55%) of the imipenem-cilastatin patients met the study’s primary endpoint (combination of clinical response and microbiological response at time of cure). Researchers reported an 18.58% adjusted treatment difference (95% CI 8.23-28.92; P = 0.0004). 

Cefiderocol was well-tolerated. In the cefiderocol group, 122 (41%) patients experienced adverse events, and among imipenem-cilastatin patients, 76 (51%) patients did. Gastrointestinal disorders were the most common adverse events in both groups (35 [12%] patients in the cefiderocol group and 27 [18%] patients in the imipenem-cilastatin group). 

Lead study author Dr. Simon Portsmouth called cefiderocol a “trojan horse.” 

“The drug uses a novel mechanism of cell entry that takes advantage of the bacteria’s need for iron to survive,” Dr. Portsmouth said. “During an acute infection, one of our innate immune responses is to create an iron-poor environment. In response, bacteria increase their iron intake. Cefiderocol binds to irons and is transported through the extra outer membrane by the bacterium’s own iron-transport system. These iron channels also enable the drug to bypass the bacteria’s porin channels and gain repeat entry even if the bacterium has evolved efflux pumps.” 

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Sources: The Lancet Infectious DiseasesBioSpaceMedical News Today

Kaitlyn D’Onofrio is a digital medical writer. She is interested in musculoskeletal health, the effect of exercise on health, and mental health awareness. When she’s not writing for DocWire, Kaitlyn is teaching yoga classes in her community, promoting wellness to her students.