Strength in Numbers: Scientists Combine Ineffective Antibiotics to Defeat Superbugs

Novel combinations kill ESKAPE bacteria

In the fight against super bacteria, scientists at the University at Buffalo (UB) are relying on strength in numbers to overcome drug resistance. The researchers have found that combinations of three antibiotics––each of which is ineffective against “superbugs” when used alone––are capable of eradicating two of the six ESKAPE bacteria when delivered together.

ESKAPE bacteria comprise a group of antimicrobial-resistant pathogens that pose a grave threat, causing more than two million infections and nearly 23,000 deaths a year, according to the Centers for Disease Control and Prevention. The six super bacteria are also responsible for a substantial number of infections in hospitals.

“These bacteria are extremely problematic and have become resistant to nearly all available antibiotics. We needed to think differently to attack this problem,” said Brian Tsuji, PharmD, an author on two recent studies and an associate professor at the UB School of Pharmacy and Pharmaceutical Sciences. One study was published in the May issue of the Journal of Antimicrobial Chemotherapy, and the other study was published in the April issue of Antimicrobial Agents and Chemotherapy.

Nontraditional combinations of medication are often used to fight superbug infections; questions remain, however, regarding proper dosage and which combinations are most effective.

The researchers tested combinations of the antibiotics polymyxin B, meropenem, and ampicillin–sulbactam against the pathogen Acinetobacter baumannii. The bacterium Klebsiella pneumoniae was treated with polymyxin B, meropenem, and rifampin. Each antibiotic was chosen to complement the other drugs’ mechanisms of bacterial killing.

The researchers applied the medications to bacterial samples individually, in pairs, and in triple combinations. They then measured both the time needed for the antibiotics to kill the bacteria and the time it took for the pathogens to repopulate.

For the tests on A. baumannii, none of the antibiotics was able to kill the bacteria when used alone. Of the pairs of antibiotics, only the grouping of polymyxin B and meropenem was able to effectively kill the pathogens, but the bacteria gradually regrew over three days.

The triple combination achieved a kill rate similar to that of polymyxin B and meropenem, but the addition of ampicillin–sulbactam prevented regrowth of the pathogen. Within 96 hours, no viable bacteria cells were detected after exposure to all three antibiotics.

In the tests against K. pneumoniae, the individual antibiotics were unable to sustain the killing of bacteria during a 24-hour period. The most effective double combination was polymyxin B and rifampin, which killed bacteria for up to 30 hours before the population regrew to initial levels.

The triple combination of polymyxin B, meropenem, and rifampin produced the highest kill rates and tripled the time it took for bacteria to regrow (to 72 hours). Rifampin, the researchers suspect, temporarily suppresses the antibiotic resistance of K. pneumoniae, allowing the trio to destroy the bacteria.

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

Source: Medical Xpress; May 24, 2017.