Scientists find link between increases in local temperature and antibiotic resistance

From Vector, the Boston Children’s clinical and research innovation blog

BY KAT J. MCALPINE | MAY 21, 2018

Over-prescribing has long been thought to increase antibiotic resistance in bacteria. But could much bigger environmental pressures be at play?

While studying the role of climate on the distribution of antibiotic resistance across the geography of the U.S., a multidisciplinary team of epidemiologists from Boston Children’s Hospital found that higher local temperatures and population densities correlate with higher antibiotic resistance in common bacterial strains. Their findings were published today in Nature Climate Change.

“The effects of climate are increasingly being recognized in a variety of infectious diseases, but so far as we know this is the first time it has been implicated in the distribution of antibiotic resistance over geographies,” says the study’s lead author, Derek MacFadden, MD, an infectious disease specialist and research fellow at Boston Children’s Hospital. “We also found a signal that the associations between antibiotic resistance and temperature could be increasing over time.”

During their study, the team assembled a large database of U.S. antibiotic resistance in E. coli, K. pneumoniae and S. aureus, pulling from hospital, laboratory and disease surveillance data documented between 2013 and 2015. Altogether, their database comprised more than 1.6 million bacterial specimens from 602 unique records across 223 facilities and 41 states.

Rising temperatures, rising antibiotic resistance

Not surprisingly, when looking at antibiotic prescription rates across geographic areas, the team found that increased prescribing was associated with increased antibiotic resistance across all the pathogens that they investigated.

But then, after adjusting for prescriptions rates and other factors, when the team mapped out the latitude coordinates and mean and median local temperatures of their data points, they found that higher local average minimum temperatures correlated strongly with antibiotic resistance. Local average minimum temperature increases of 10 degrees Celsius (50 degrees Fahrenheit) were associated with 4.2, 2.2 and 3.6 percent increases in antibiotic resistant strains of E. coli, K. pneumoniae, and S. aureus, respectively.

“Estimates outside of our study have already told us that there will already be a drastic and deadly rise in antibiotic resistance in coming years,” says the paper’s co-senior author John Brownstein, PhD, chief innovation officer and director of the Computational Epidemiology Group at Boston Children’s and professor of pediatrics at Harvard Medical School (HMS). “But with our findings that climate change could be compounding and accelerating an increase in antibiotic resistance, the future prospects could be significantly worse than previously thought.”

Population growth = more chances for antibiotic resistance to spread?

More unsettling still were some newly-discovered associations with population density. The team found that an increase of 10,000 people per square mile was associated with three and six percent respective increases in antibiotic resistance in Gram-negative E. coli and K. pneumoniae. In contrast, population density did not appear to significantly affect the antibiotic resistance of Gram- positive S. aureus.

The Gram method of differentiating bacteria — named after the method’s inventor, a scientist named Hans Christian Gram — uses a violet dye to tell whether a bacterial species has a cell wall made up of thin or thick layers. Thicker Gram-positive bacteria, which are so-called because they retain more of the violet dye than their thinner Gram-negative counterparts, are typically more susceptible to antibiotics because despite their thickness, they lack an outer cell membrane.

“Population growth and increases in temperature and antibiotic resistance are three phenomena that we know are currently happening on our planet,” says the study’s co-senior author Mauricio Santillana, PhD, who is a faculty member in the Computational Health Informatics Program at Boston Children’s and an assistant professor at HMS. “But until now, hypotheses about how these phenomena relate to each other have been sparse. We need to continue bringing multidisciplinary teams together to study antibiotic resistance in comparison to the backdrop of population and environmental changes.”

Image showing correlation between rising population and urban growth in the southern U.S., which could be linked to rising antibiotic resistance — MacFadden says transmission factors are of particular interest for further scientific research.

“As transmission of antibiotic resistant organisms increases from one host to another, so does the opportunity for ongoing evolutionary selection of resistance due to antibiotic use,” MacFadden says. “We hypothesize that temperature and population density could act to facilitate transmission and thus increases in antibiotic resistance.”

“The bottom line is that our findings highlight a dire need to invest more research efforts into improving our understanding of the interconnectedness of infectious disease, medicine and our changing environment,” Brownstein concludes.

In addition to MacFadden, Brownstein and Santillana, additional authors on the study are Sarah McGough and David Fisman.

This work was supported by a Canadian Institute for Health Research Fellowship, the Clinician Scientist Program at University of Toronto’s Department of Medicine and the National Library of Medicine (NIH R01 LM011965).

Illustrations by Fawn Gracey.

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