New drug candidate may offer better way to fight stubborn infections, study says

Aug. 10 (UPI) -- A new drug candidate able to fight off more than 300 types of drug-resistant bacteria in the laboratory may be used one day to treat stubborn infections in humans, researchers said Wednesday.

The compound, fabimycin, targets gram-negative bacteria, which are difficult to treat and responsible for conditions including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis, according to the Centers for Disease Control and Prevention.

To begin its work, a research team led by the University of Illinois at Urbana-Champaign made a series of structural modifications to an antibiotic active against gram-positive bacteria, thinking this would allow it to act against gram-negative strains.

Fabimycin, one of the modified compounds, "proved potent against more than 300 drug-resistant clinical isolates, while remaining relatively inactive toward certain gram-positive pathogens and some typically harmless bacteria that live in or on the human body," said a news release on the study, published in ACS Central Science, a journal of the American Chemical Society.

In their scientific paper, the researchers noted that so-called "FabI inhibitors" -- from which the fabimycin compound emerged -- have advanced to clinical trials for Staphylococcus aureus infections, but not for infections caused by gram-negative bacteria.

Gram-negative bacteria have a "formidable outer membrane" that keeps most antibiotics out and "pumps" that remove those antibiotics able to get inside, the researchers said.

The problematic pathogens also can mutate to evade multiple drugs, and even those treatments that work may eradicate many kinds of bacteria, including beneficial ones.

The scientists' aim was to design a drug able to infiltrate the defenses of gram-negative bacteria and treat infections, while leaving helpful microbes intact, the release said.

In fact, fabimycin reduced the amount of drug-resistant bacteria in mice with pneumonia or challenging urinary tract infections to pre-infection levels or below, the release said.

The study's abstract specifically noted its "impressive activity" against clinical isolates of Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii.

Researchers said their work provides additional evidence that antibiotics can be systematically modified to kill problematic gram-negative bacteria.

The CDC began monitoring drug-resistant gram-negative bacteria in 2011, and last year the agency reported on the rapid spread of multidrug-resistant gram-negative bacteria among patients being treated for COVID-19 in a Maryland hospital in May-June 2020.

"Critical illness, high antibiotic use, double occupancy of single rooms, and modified infection prevention practices were key contributing factors," the agency said.