A new drug combination has been shown to be more successful, especially against persistent, drug-resistant infections, according to an international study conducted by a Rutgers Researcher comparing new and older therapies for complex urinary tract infections.
Researchers from the ALLIUM Phase 3 clinical trial reported their findings in the Journal of the American Medical Association (JAMA), demonstrating that cefepime and enmetazobactam were more successful than the conventional regimen of piperacillin and tazobactam in treating complicated urinary tract infections and acute pyelonephritis (AP), a bacterial infection that causes kidney inflammation.
When urinary tract infections are accompanied by risk factors that raise the possibility of antibiotic therapy failings, such as fevers, sepsis, urinary obstruction, or catheters, they are referred to as complex urinary tract infections.
This new antibiotic was superior to the standard-of-care therapy. It represents an exciting option for treatment.”
Keith Kaye, Study Lead Author and Professor, Medicine, Rutgers Robert Wood Johnson Medical School
Kaye is also the Chief of the Division of Allergy, Immunology and Infectious Diseases.
The extended spectrum beta-lactamase (ESBL) infections, named after an enzyme the bacteria generate, are a group of frequently deadly bacterial diseases caused by pathogens. Kaye said this drug combination also combats these infections.
Many of the medicines that are typically prescribed to treat infections, like penicillin and cephalosporins, are ineffective against ESBL-producing bacteria.
Kaye added, “We are looking for antibiotics that are active against resistant bacteria, such as ESBLs, and we found this new combination to be highly effective.”
From September 2018 to November 2019, the experiment was carried out in 90 locations across Europe, North and Central America, South America, and Africa. The research had more than a thousand patients.
Approximately 79% of the patients getting the new combination of cefepime and enmetazobactam, compared to 58.9% of those receiving the traditional combination of piperacillin and tazobactam, were effectively treated for their illness.
Of the 20% of patients from the total group who belonged to the subgroup of those with ESBL infections, 73% of the patients getting cefepime and enmetazobactam, as compared to 51% of the patients receiving conventional treatment, attained a clinical cure.
A fourth-generation cephalosporin antibiotic with generic availability, cefepime was authorized for usage in the 1990s. The beta-lactamase inhibitor enmetazobactam, manufactured by the French biopharmaceutical company Allecra Therapeutics, targets beta-lactamases, including the types of enzymes generated by ESBL-producing bacteria.
The US Food and Drug Administration (FDA) has designated the drug combination as a Qualified Infectious Disease Product and given it Fast Track status.
Kaye stated that the company will submit an application for FDA approval early in the next year.
According to a study from the US Centers for Disease Control and Prevention (CDC), more than 2.8 million antimicrobial-resistant infections occur in the US every year, and more than 35,000 people pass away as a result of them. According to a 2019 study on antibiotic resistance, ESBLs pose a major risk to human health.
Appreciating the Rutgers-led study, a JAMA editorial by Sonali Advani and Kimberly Claeys, both of Duke University School of Medicine, stated, “The clinical trial by Kaye et al presents a promising novel antibiotic therapy that expands the limited armamentarium for resistant organisms and an exciting new therapeutic option for the management of acute pyelonephritis or complicated [urinary tract infection].”
Kaye, K. S., et al. (2022). Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis. Journal of the American Medical Association. doi.org/10.1001/jama.2022.17034