Combination therapy in the face of growing antibiotic resistance

Combination therapy in the face of growing antibiotic resistance

Originally published on Technology Networks  

Bacteria—especially Gram-negative strains—are becoming increasingly resistant to current antibiotic drugs, and the development of new classes of antibiotics has slowed. Faced with these challenges, investigators are studying the potential of combination therapy, in which two or more drugs are used together to increase or restore the efficacy of both drugs against a resistant bacterial pathogen. Now new research indicates that such synergy may work even when bacteria become resistant to colistin, which is considered a treatment agent of last resort.

The findings are especially promising because recent evidence indicates the potential for rapid worldwide spread of colistin resistance. “For an infected patient, if the multidrug-resistant Gram-negative bacterial pathogen is resistant to colistin, then there is a big problem,” said senior author James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC.

In their Antimicrobial Agents and Chemotherapy study, Kirby and his colleagues Thea Brennan-Krohn, MD and Alejandro Pironti, PhD screened 19 different antibiotics for synergy with colistin. The team discovered several combinations where synergy was present and infections with resistant pathogens could potentially be treated with the combination therapy.

Of particular interest, colistin demonstrated high rates of synergy with linezolid, fusidic acid, and clindamycin, which are protein synthesis inhibitor antibiotics that individually have no activity against Gram-negative bacteria. “It was remarkable to see two drugs, each of which is inactive on its own against these bacteria, inhibiting them in combination,” notes Brennan-Krohn. “These findings suggest that colistin retains sub-lethal activity against colistin-resistant bacteria, which may enable drugs like linezolid to reach their targets.”

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