Microbes and Antibiotic Resistance

Infectious bacteria that are down but not quite dead yet may be more dangerous than previously thought. Even as one antibiotic causes the bacteria to go dormant, the microbes may more easily develop resistance to another drug, according to new research. Deadly Staphylococcus aureus bacteria that could tolerate one type of antibiotic developed resistance to a second antibiotic nearly three times faster than fully susceptible bacteria did, researchers report in the Jan. 10 Science. The findings could suggest why drug cocktails used to knock out infections quickly sometimes fail, and may eventually lead to changes in the way antibiotics are prescribed in certain situations.

Such tolerant bacteria may be the source of lingering or recurring infections and especially affect people with weakened immune systems or those with medical implants, such as joint replacements. Doctors may try giving drug cocktails to turn the tide of this sort of infection, particularly for hard-to-kill tuberculosis.

In previous lab experiments, scientists found that tolerant bacteria were more likely to develop antibiotic resistance. This happens in patients, too, the new study finds. Doctors used the powerful antibiotic vancomycin to treat two patients who were admitted between May 2017 and May 2018 to Shaare Zedek Hospital in Jerusalem with methicillin-resistant S. aureus, or MRSA, infections in their bloodstreams. Within days, the patients’ bacteria became tolerant to the drug. One patient, a 63-year-old woman with a recently implanted heart defibrillator, was switched to the antibiotic daptomycin. It turns out that her bacteria were also tolerant to that drug. So rifampicin was added to the mix. The patient’s bacteria quickly became resistant to rifampicin. In lab experiments, it took just seven cycles of treatment with rifampicin for the woman’s daptomycin- and vancomycin-tolerant bacteria to develop rifampicin resistance. In comparison, it took 20 cycles for nontolerant bacteria to develop resistance. Similarly, the other patient’s infection developed tolerance before resistance.

CITATIONS J. Liu et al. Effect of tolerance on the evolution of antibiotic resistance under drug combinations. Science. Vol. 367, January 10, 2020, p. 200. doi:10.1126/science.aay3041. A.D. Berti and E.B. Hirsch. Tolerance to antibiotics affects response. Science. Vol. 367, January 10, 2020, p. 141. doi:10.1126/science.aba0150.