New drugs have been found to be effective in treating complex urinary tract infections

An international study led by a Rutgers scientist compared old and new treatments for complex urinary tract infections and found a new combination of drugs that were more effective, especially against stubborn drug-resistant infections
.

The investigators of the ALLIUM Phase 3 clinical trial described the results in the Journal of the American Medical Association (JAMA), showing that the combination of cefepime and enmetazobactam for complex urinary tract infections and acute pyelonephritis (a bacterial infection that causes inflammation of the kidneys) is more effective
than standard treatment with combination therapy with piperacillin and tazobactam.
Urinary tract infections are considered complex when they are associated with risk factors, including fever, sepsis, urinary tract obstruction, or urinary catheterization, which increase the risk of
antibiotic treatment failure.

"This new antibiotic is superior to standard care therapies," says Keith Kaye, director of the Department of Allergy, Immunology and Infectious Diseases and Infectious Diseases, "which represents an exciting treatment option.
"

Kaye added that the drug combination could also combat a often dangerous bacterial disease caused by pathogens known as broad-spectrum β-lactamase (ESBL) infections, named
after an enzyme produced by bacteria.
Esbl-producing bacteria cannot be effectively killed by many antibiotics traditionally used to treat infections, such as penicillins and cephalosporins
.

"We were looking for antibiotics that were effective against drug-resistant bacteria, such as ESBLs, and we found this new combination to be very effective
," Kaye said.

The trial was conducted
at 90 sites in Europe, North and Central America, South America and South Africa between September 2018 and November 2019.
More than 1,000 patients participated in the study
.
About 79% of patients who received a new combination of cefepime and emmetabactam successfully cured their disease, compared with 58.
9%
of patients who received traditional treatment with piperacillin and tazobactam.

Twenty percent of patients in the entire group belonged to a subpopulation of ESBL infection, with 73 percent of patients treated with cefepime and emmetabactam achieving a clinical cure
, compared with only 51 percent of those receiving standard treatment.

The antibiotic cefepime, a fourth-generation cephalosporin, was approved for use in the 90s and has now become a universal drug
.
Enmetazobactam, an experimental drug produced by French biopharmaceutical company Allecra Therapeutics, is an β-lactamase inhibitor, meaning it attacks β-lactamase, including various enzymes
produced by bacteria that produce esbl.
The drug combination has been recognized as a Qualified Infectious Disease Product and Fast Track designation
by the U.
S.
Food and Drug Administration (FDA).

Kaye said he expects the company to apply to the FDA for approval
early next year.

According to a report by the Centers for Disease Control and Prevention (CDC), more than 2.
8 million drug-resistant infections occur in the United States each year, and more than 35,000 people die from drug-resistant infections
.
In a 2019 study on antibiotic resistance, the U.
S.
Centers for Disease Control and Prevention characterized ESBLs as a serious threat
to human health.

An editorial published in the Journal of the American Medical Association by Sonali Advini and Kimberly Claeys of Duke University School of Medicine praised the Rutgers-led study: "The clinical trial by Kaye et al.
proposes a promising novel antibiotic therapy that expands the therapeutic reach of limited drug-resistant microorganisms and offers exciting new treatment options
for the management of acute pyelonephritis or complications (urinary tract infections).
"

Effect of Cefepime/Enmetazobactam vs Piperacillin/Tazobactam on Clinical Cure and Microbiological Eradication in Patients With Complicated Urinary Tract Infection or Acute Pyelonephritis A Randomized Clinical Trial JAMA