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Bicarbonate boost for spurned antibiotic

In bicarbonate’s presence, azithromycin kills microorganisms thought to be drug resistant

by XiaoZhi Lim, special to C&EN
October 8, 2020 | A version of this story appeared in Volume 98, Issue 39

Structure of azithromycin

Bicarbonate, ubiquitous in the body, helps the antibiotic azithromycin kill apparently resistant bacteria, including the multidrug-resistant Pseudomonas aeruginosa (ACS Infect. Dis. 2020, DOI: 10.1021/acsinfecdis.0c00340). Azithromycin is often cast aside because of a perception that many bacteria are resistant to antibiotics in its category. Eric D. Brown of McMaster University and colleagues found that adding physiological amounts of bicarbonate to bacterial cultures allowed azithromycin to kill 90% of Staphylococcus pneumoniae, Pseudomonas aeruginosa, and methicillin-resistant S. aureus strains at one sixty-fourth the levels that were necessary without bicarbonate, a “whopping difference,” Brown says.

His group has previously shown that bicarbonate makes it easier for positively charged antibiotics to enter cells. Bicarbonate also reduces the pH gradient across the cell membrane, robbing bacterial efflux pumps of the energy they need to clear antibiotics from their cells, Brown explains.

Bicarbonate levels on skin are lower than in the body, so the team tested whether bicarbonate could help with topical infections. A mixture of azithromycin and bicarbonate applied to mouse wounds infected with multidrug-resistant P. aeruginosa killed 99.9% of bacteria cells, compared with 99% of cells without bicarbonate. Reached via email, Michael Mahan of the University of California, Santa Barbara, says that standard tests of antibiotic effectiveness should be redesigned to include bicarbonate and other microenvironmental factors in our bodies.


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