Antibiotic resistance increases by climate change

​An interesting article documented an association between antibiotic resistance and temperature increases (see antibiotic resistance and global warming natureclimchange2018 in dropbox, or MacFadden DR. Nature Climate Change; 2018: 510). This adds to some other clinical effects of climate change, such as the migration of tropical diseases (eg, malaria, dengue) to now warmer areas (eg, Southern US). [thanks to Paul Susman for passing this article on to me]

Details:
-- the researchers developed a large database of antibiotic resistance patterns across the United States, using data from hospitals, laboratories, and surveillance units.
-- resistance indices were linked with facility characteristics (e.g. inpatient/outpatient) as well as regional antibiotic prescribing rates and population density
-- the dataset represents over 1.6 million clinically relevant bacterial pathogens from 602 unique records that span 223 facilities across 41 states, for the years 2013-2015
-- they accessed local historical climate variables (mean and minimum temperature), averaged over the time-period 1980-2010.

Results:
-- on multivariate adjustment including prescription rate and population density, an increase in the minimum temperature of 10°C across regions of the United States was associated with:
    -- 4.2% increased antibiotic resistance in E. coli (p<0.0001)
    -- 2.2% increased resistance in Klebsiella pneumonia (p<0.0001)
    -- 5.1% increased resistance in Staphylococcus aureus (p<0.0001)
-- average minimum temperature correlated better than average temperature or latitude in terms of antibiotic resistance in these 3 bacteria
-- resistance is increasing over time
-- additionally, also in multivariable-adjusted analysis, there were increases in antibiotic resistance to cloxacillin by 5.8% (p<0.0001), fluoroquinolones by 3.7% (p=0.096, not quite statistically significant), and macrolides by 6.0% (p<0.001)
-- in terms of the antibiotics:
    ​--for E. coli, the highest rates of resistance were for trimethoprin-sulfa, amoxicillin, tetracyclines, ampicillin-sulbactam, gentamicin, tobramycin, and levofloxacin
    --for K. pneumoniae, the highest rates were for gentamicin, ceftazidime, trimethoprim-sulfa, ampicillin-sulbactam, levofloxacin, tobramycin, and cephalexin
    ​--for S. aureus: quinupristin/dalfupristin, erythromycin, trimethoprim-sulfa, cloxacillin, nitrofurantion, cephalexin and levoflaxacin
-- an increase in population density by 10,000 persons per square mile was associated with 6% increase in antibiotic resistance to K. pneumonia (p<0.0001), and a 3% increase in E. coli (almost significant at p=.0.86)

Commentary:
-- antimicrobial resistance causes significant morbidity and mortality, is currently associated with 700,000 people dying each year across the world, and has estimates of attributable mortality for up to 10 million people by the year 2050

--this study found that  increasing local temperature as well as population density are associated with increased antibiotic resistance

-- Antibiotic resistance in bacteria is largely due to use of antibiotics, many of which are overused both in livestock as well as in humans, as documented in many prior blogs (see below). The findings in the above study suggests that climate change may also be affecting bacterial resistance, which suggests that current forecasts of antibiotic resistance may be significantly underestimated unless climate change and a growing population are taken into account
-- proposed mechanisms:
    -- temperature is a potent motivator of bacterial growth rates and may increase transmission between humans and animals
    -- temperature facilitates horizontal gene transfer, through the exchange of resistance genes (e.g., plasmids) as in the case with plasmid born extended spectrum beta-lactamases (ESBLs), or with the uptake of free genetic material.
        -- For example, southern European countries have a higher incidence of infection from ESBL-producing Enterobacteriaceae
    -- fluoroquinolones and beta-lactams have the strongest associations between temperature and bacterial resistance
-- A study such as the above one cannot draw firm conclusions, since all variables are not controlled for, but does suggest a strong association and has a quite plausible mechanism. But, for example, temperature differences may have effects on behavioral or social factors leading to increased transmission of resistant bacteria, as perhaps by more socialization, or more interaction between humans and animals.
-- the difference of 10°C​ is a huge temperature change and is pretty unlikely to occur in one area. But the current difference of 10°C over many hundreds of miles of latitude suggests that bacterial resistance will slowly migrate to the cooler northern climates that are slowly warming.

so, this study adds to the litany of concerns about climate change. it seems to make sense that warmer temperatures matter in antibiotic resistance since a major cause of antibiotic resistance is through plasmids migrating from one bacterium to another and even crossing from one species to another. for example from the above study, E. coli develops significantly more resistance in warmer temperatures, E. coli seems to be a frequent source of these antibiotic resistance plasmids (see blogs below), and plasmids proliferate more in higher temperatures. Population density increases, also happening in much of the world, increases the problem as well (and access to effective birth control may be increasingly limited in the current political climate). Of course, this study just adds to the other major sources of bacterial resistance: overuse of antibiotics in animals in industrial farming and overuse by us guys....

for the many prior blogs on antibiotic resistance, see http://gmodestmedblogs.blogspot.com/2018/06/s-typhi-and-shigella-resistance.html which details the emergence of potentially epidemic Salmonella typhi, but also references prior blogs on the WHO report on global antibiotic resistance, increasing gonorrhea resistance, antibiotic overuse in humans and animals, the emergence of E. coli superbugs, an effective antibiotic stewardship program, etc etc.  It also highlights an interesting article suggesting that for many infections, it is better NOT to take the full course of prescribed antibiotics.

geoff​

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