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 May 23, 2018
A Warming Climate May Produce More Drug-Resistant Infections

 A person's chances of acquiring a drug-resistant infection may be higher if she lives in a warmer area.

A study appearing today in Nature Climate Change from researchers at the University of Toronto (U.T.) and Boston Children's Hospital links the emergence of drug-resistant bacteria to a hotter climate. Researchers found a 10-degree Celsius increase in daily minimum temperature was associated with a small increase in resistance in common pathogens, including those that develop into methicillin-resistant Staphylococcus aureus (MRSA), the root of many persistent and sometimes deadly hospital infections. "This is a very important and timely study stemming from meticulously collected and arranged records of antibiotic resistance," says Elena Naumova, an epidemiologist at Tufts University who was not involved in the work. "What's great about this study is that they really broaden the concept of antibiotic-resistance patterns."

Scientists have long observed bacteria in the laboratory grow and reproduce more quickly at warmer temperatures. And increased growth can cause a hike in resistant strains when DNA mutations crop up during reproduction. Bacteria can also swap DNA with one another and spread resistance via a process called horizontal gene transfer, which also increases at higher temperatures. Now scientists are asking if this phenomenon also occurs outside the laboratory.

The research was enabled by a large-scale data collection effort to create a free and open Web-based application that gives the geographical locations of drug-resistant bacteria. The site, called Resistance Open, allows anyone in the world to punch in their postal code and see which drug-resistant infections are present in their hometown. "For a physician, they can have a better understanding of what is happening in the community rather than just in their hospital," says John Brownstein, a professor of medicine at Harvard Medical School and co-senior author of the study. And the tool allows scientists to see new patterns in drug resistance, such as how it may be affected by climate.

The team first had to scour hospital records for the results of clinical sensitivity tests---diagnostics to determine how well various antibiotics work against bacterial infections. This was a labor-intensive and time-consuming task as most hospitals keep this data locked in pdf files that are difficult to access with current data-mining tools. In the end, the team collected data from 223 different facilities across 41 states. They analyzed the results of 22.8 million diagnostic tests representing 1.6 million bacterial strains. The researchers focused on three of the most common drug-resistant strains: Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus, which are known to cause drug resistant urinary, skin and blood infections, respectively.

They found a 10-degree C increase in temperature was associated with increases in antibiotic resistance of 4, 2 and 3 percent for E. coli, K. pneumoniae and S. aureus, respectively. Minimum temperature was used because it is a more accurate predictor of the persistence and continued growth of bacteria than is average temperature, which can represent big swings in highs and lows. The effect was significant even after the researchers controlled for antibiotic prescription rate, population density and laboratory standards. "Places in the South tend to show more resistance than places in the North, and a good chunk of that variability can be explained by temperature," Brownstein says.

In a separate analysis his team found an uptick in population density by 10,000 persons per square mile was independently linked to a 3 to 6 percent increase in resistance. They posit increased bacterial transmission may have occurred in more densely populated areas. The researchers also found overprescription leads to increased resistance. Taken together, the findings suggest these three factors---temperature, population density and prescription rates---are all responsible for driving the growth of drug-resistant bacteria.

The results spell trouble for a world that is growing hotter and more crowded. Derek MacFadden, an infectious disease expert at U.T. and a co-lead author of the study, stresses current estimates of the spread of drug-resistant infections may be understated because they do not take into account the warming climate and population growth.

"The minimum temperatures are going to keep going up. We will have increased population density and there is evidence that antibiotic prescription rates are going up," says Lance Price, a biologist at The George Washington University who was not involved in the study. "So I think that we are going to have a problem." He stresses that curbing antibiotic use in humans and farm animals is one thing we can do now to help this escalating issue: "If we don't take care of this, then the piece that will change will be population density, because people will be dying."