A new, more effective UTI drug

An international study led by a researcher at Rutgers University shows that a new drug combination has been shown to be more effective, especially against recalcitrant drug-resistant infections
.
The study compared old and new treatments
for complex urinary tract infections.

The researchers in the ALLIUM Phase 3 clinical trial published their findings in the Journal of the American Medical Association (JAMA), demonstrating that cefepime and enmetaobactam are more successful
than traditional piperacillin and tazobactam in treating complex urinary tract infections and acute pyelonephritis, a bacterial infection that causes inflammation of the kidneys.
Urinary tract infections are considered complex when combined with risk factors such as fever, sepsis, urinary tract obstruction, or urinary catheters, all of which increase the likelihood of
antibiotic failure.

Keith Kaye, professor of medicine and chief of the Division of Allergy, Immunology and Infectious Diseases at Rutgers Robert Wood Johnson Medical School, said: "This new antibiotic is superior to standard care therapy
.
"

"This represents an exciting treatment option," said
Kaye, the study's principal investigator and lead author of the publication.

According to Kaye, the drug combination also fights a often dangerous bacterial disease caused by a pathogen known as a broad-spectrum β-lactamase (ESBL) infection, named after
an enzyme produced by the bacteria.
Many antibiotics used to treat infections, such as penicillins and cephalosporins, are ineffective
against the bacteria that produce ESBL.

"We are looking for antibiotics that are effective against resistant bacteria, such as ESBLs, and we found that this new combination is 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 combination of cefepime and emmetabactam successfully cured their disease, compared with 58.
9%
of patients receiving traditional therapy with piperacillin and tazobactam.

In the overall group, 20% of patients belonged to a subgroup of ESBL infection, and 73% of patients treated with cefepime and emmetabactam achieved clinical cure
, compared with only 51% of patients receiving standard care.

The antibiotic cefepime is a fourth-generation cephalosporin that was approved for use in the 90s and is now a universal drug
.
Enmetazobactam, an experimental drug made by French biopharmaceutical company Allecra Therapeutics, is a β-lactamase inhibitor, meaning it attacks β-lactamase, including various enzymes
produced by the bacteria that produce esbl.
The drug portfolio has been awarded 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 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 Advani and Kimberly Claeys of Duke University School of Medicine praised the Rutgers-led study: "The clinical trial of Kaye et al.
proposes a promising new antibiotic therapy that expands the therapeutic scope of limited resistant microorganisms and provides exciting new treatment options
for the management of acute pyelonephritis or complex (urinary tract infections).
"

Original:

“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” by Keith S.
Kaye, MD, Adam Belley, Ph.
D.
, Philip Barth, Ph.
D.
, Omar Lahlou, PharmD, Philipp Knechtle, Ph.
D.
, Paola Motta, Ph.
D.
and Patrick Velicitat , MD, 4 October 2022, JAMA.

DOI: 10.
1001/jama.
2022.
17034

“Cefepime/Enmetazobactam for Complicated Urinary Tract Infections” by Sonali D.
Advani, MBBS, MPH and Kimberly Claeys, PharmD, 4 October 2022, JAMA.

DOI: 10.
1001/jama.
2022.
15228