New adjuvants may help fight drug-resistant bacteria

A pair of synthetic compounds can be administered with some antimicrobials to combat Staphylococcus resistant to the drugs, according to a recent study.

An article published March 9 (Sci Transl Med 2016;8:329ra32) indicates researchers for Merck identified a pair of chemicals that inhibit the first step in the development of teichoic acid, a polymer in bacterial cell walls. Those synthetic compounds, tarocin A and B, lack bioactivity on their own. But, when they are administered with a broad-spectrum ß-lactam antimicrobial, that combination is a potent killer of Staphylococcus isolates that otherwise would be resistant to the antimicrobial.

“Mechanistically, tarocins likely reset the susceptibility of methicillin-resistant staphylococci to ß-lactams by antagonizing multiple aspects of cell wall biosynthesis, regulation, and remodeling that ultimately compromise the physical strength of the bacterial cell wall,” the article states.

Further increasing tarocin potency could increase susceptibility among methicillin-resistant S aureus and S epidermidis isolates, the article states.

In vitro test results revealed that the ß-lactam and tarocin combinations were efficacious against MRSA and MRSE isolates and “largely unaffected by spontaneous resistance” or substantial differences among isolates, the article states. Even staphylococci resistant to the combination of tarocin and a ß-lactam drug likely would have weakened cell walls following administration of the combination, increasing their vulnerability to host immune responses and macrophages.

The authors also indicated about 82 percent of MRSA isolates and 77 percent of MRSE isolates tested were susceptible to a combination of dicloxacillin and tarocin A2, a more soluble analog, although those isolates had varied susceptibilities to the combination.

The combination of dicloxacillin and tarocin A2 also was effective at treating MRSA in mice.