Triple-Antibiotic Combos Eliminate Two Treatment-Resistant Bacteria

Triple-Antibiotic Combos Eliminate Two Treatment-Resistant Bacteria

A combination of three antibiotics can eradicate two of today’s six most treatment-resistant bacteria, according to researchers at the State University of New York at Buffalo.

Drug-resistant pneumonia returned after being wiped out, however.

The six most treatment-resistant bacteria are known as the ESKAPE pathogens. The acronym come from the first letter of each type: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species.

Alone, the three antibiotics were ineffective against drug-resistant bacteria. When combined, they were potent against the pathogens responsible for several serious infections, including pneumonia.

The findings were reported in two studies. One, “Polymyxin-resistant, carbapenem-resistant Acinetobacter baumannii is eradicated by a triple combination of agents that lack individual activity,” was published in the Journal of Antimicrobial Chemotherapy. The other, Polymyxin B-Based Triple Combinations Wage War Against KPC-2-producing Klebsiella pneumoniae: New Dosing Strategies for Old Allies,” was published in Antimicrobial Agents and Chemotherapy.

“These bacteria are extremely problematic and have become resistant to nearly all available antibiotics. We needed to think differently to attack this problem,” Brian Tsuji, senior author of the two studies, said in a news report written by Marcene Robinson. Tsuji is an associate professor at the University at Buffalo School of Pharmacy and Pharmaceutical Sciences.

Scientists have developed a number of drugs in the past several decades to fight bacteria-generated infections. But their widespread use has prompted bacteria to develop ways to counter them. A number have now become drug-resistant.

Researchers have tried to combine therapies to fight superbug infections. The question is what are the right combinations and doses.

The Buffalo researchers tested a combination of the antibiotics polymyxin B, Merrem (meropenem) and Unasyn (ampicillin-sulbactam) against Acinetobacter baumannii. They also tested polymyxin B, Merrem and Rifadin (rifampin) against Klebsiella pneumoniae.

“Each antibiotic was chosen to complement the other drugs’ mechanisms of bacterial killing,” said Justin Lenhard, first author of the investigation on Acinetobacter baumannii. “By combining antimicrobials that exert their bacterial killing in different ways, it is possible to outmaneuver the ESKAPE pathogens and completely overwhelm the bacteria’s defensive countermeasures.”

The triple combination killed Acinetobacter baumannii bacteria, and prevented it from regrowing.

Klebsiella pneumoniae were more resistant. Although polymyxin B, Merrem, and Rifadin killed the bacteria, it was able to regrow within 72 hours.

“These new antibiotic combinations may help to guide therapy in infections where no treatments appear to exist,” Tsuji said.

More studies are needed to confirm the findings and to evaluate the combos’ ability to fight other strains of bacteria.

This research was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.


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