A new drug combination has been found to be more effective, especially against persistent, drug-resistant infections, according to an international study led by a Rutgers scientist comparing new and older treatments for complicated 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 complicated urinary tract infections.
"This new antibiotic was superior to the standard-of-care therapy," said Keith Kaye, chief of the Division of Allergy, Immunology, and Infectious Diseases and a professor of medicine at Rutgers Robert Wood Johnson Medical School.
"It represents an exciting option for treatment," said Kaye, the principal investigator of the study and lead author of the publication.
The extended-spectrum beta-lactamase (ESBL) infections, so named after an enzyme the bacteria produce, are a group of frequently dangerous bacterial illnesses caused by pathogens. Many of the antibiotics commonly used to treat infections, like penicillins and cephalosporins, are ineffective against ESBL-producing bacteria.
"We are looking for antibiotics that are active against resistant bacteria, such as ESBLs, and we found this new combination to be highly effective," Kaye said.
From September 2018 to November 2019, the trial was conducted at 90 locations in Europe, North and Central America, South and Central America, and South Africa. The study included over a thousand patients. As opposed to 58.9% of patients receiving the standard treatment of piperacillin and tazobactam, approximately 79% of patients receiving the novel combination of cefepime and enmetazobactam had their illness successfully treated.
Of the 20% of patients from the total group who belonged to the subset of those with ESBL infections, 73% of the patients receiving cefepime and enmetazobactam, and only 51% of the patients receiving standard therapy were clinically cured.
A fourth-generation cephalosporin antibiotic with generic availability, cefepime was authorized for use in the 1990s. The beta-lactamase inhibitor enmetazobactam, produced by the French biopharmaceutical company Allecra Therapeutics, targets beta-lactamases, including the kinds of enzymes made by ESBL-producing bacteria. The U.S. Food and Drug Administration has designated the drug combination as a Qualified Infectious Disease Product and given it Fast Track status (FDA).
Kaye predicted that the business would apply for FDA approval early in the following year.
According to a report from the US Centers for Disease Control and Prevention, 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 (CDC). According to a 2019 study on antibiotic resistance, ESBLs pose a serious risk to human health.
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