Rates of increase of antibiotic resistance and ambient temperature in Europe: a cross-national analysis of 28 countries between 2000-2016

Abstract

Background. Widely recognized as a major public health threat globally, the rapid increase of antibiotic resistance in bacteria could soon render our most effective method to combat infections obsolete. Factors influencing the burden of resistance in human populations remain poorly described, though temperature is known to play an important role in mechanisms at the bacterial level. Methods. We performed an ecologic analysis of country level antibiotic resistance prevalence in 3 common bacterial pathogens across 28 countries in Europe, and used multivariable models to evaluate associations with minimum temperature and other predictors over a 17-year period (2000-2016). We quantified the effects of minimum temperature, population density, and antibiotic consumption on the rate of change of antibiotic resistance across geographies. Findings. For three common bacterial pathogens and four classes of antibiotics, we found evidence of a long-term effect of ambient minimum temperature on rates of increase of antibiotic resistance across 28 countries in Europe between 2000-2016. Specifically, we show that across all antibiotic classes for the pathogens E. coli and K. pneumoniae, European countries with 10°C warmer ambient temperatures have experienced more rapid increases in antibiotic resistance over the 17-year period, ranging between 0.33%/year (95% CI 0.2, 0.5) and 1.2%/year (0.4, 1.9), even after accounting for recognized drivers of resistance including antibiotic consumption and population density. We found a decreasing relationship for S. aureus and methicillin of -0.4%/year (95% CI -0.7, 0.0), reflecting widespread declines in MRSA across Europe over the study period. Interpretation. Ambient temperature may be an important modulator of the rate of change of antibiotic resistance. Our findings suggest that rising temperatures globally may hasten the spread of resistance and complicate efforts to mitigate it. Funding. Canadian Institutes of Health Research Fellowship (D.R.M.). Research in context:Evidence before this study While multiple studies have independently pointed out associations between temperature and bacterial biological cycles, few studies have focused on characterizing the relationship of ambient temperature and antibiotic resistance on a multi-geography or multi-country scale. We performed a general search on MEDLINE using the joint keywords "antibiotic resistance" and "climate" for original research published up to June 22, 2018. A recent study conducted in the US identified that locations with warmer ambient temperatures experienced higher values of antibiotic resistance prevalence using three years of data, and one European country-level analysis discovered that higher distance from the equator was a predictor for lower risk of Acinetobacter spp. resistance to carbapenems.

Levels of outpatient prescribing for four major antibiotic classes and rates of septicemia hospitalization in adults in different US states

“…Our work also suggests that average minimal daily temperature is positively associated with the rates of septicemia hospitalization in four out of five age groups of adults, which resonates with earlier findings about the association between temperature and antibiotic resistance [35,36,19].…”

“…Besides the antibiotic prescribing rates, the other covariates used in the model were the state-specific median household income, the statespecific average minimal daily temperature, and percentages of state residents in a given age group who were African American, as well as those who lacked health insurance (for age groups under 65 years). We note that temperature may influence bacterial growth rates and/or transmission mediated effects [35,36], which in turn may affect both the prevalence of antibiotic resistance and the acquisition/severity of bacterial infections. We also note that African Americans have elevated rates of sepsis compared to other races [37].…”

Antimicrobial resistance of Klebsiella Pneumoniae Pathogens in 2019 of Shaoxing City, Zhejiang Province: A Multi-Centre, Retrospective Study

“…Data from 66 hospitals in Shanghai show that the separation rate of ESBLs-KP derived from sputum, blood, and urine increased year by year from 2015 to 2017 [9]. The change in antibiotic resistance rates over 17 years (2000-2016) from EARSNet was becoming more and more serious, and that the resistance rates to thirdgeneration cephalosporins, uoroquinolones, and aminoglycosides showed a signi cant upward trend, and the analysis was related to ambient temperature [10].…”

“…With increasing drug resistance makes clinical anti-infective treatment has become a more di cult problem. Especially carbapenem-resistant K. pneumoniae bloodstream infections are accompanied by higher mortality [10].…”

The relation between prescribing of different antibiotics and rates of mortality with sepsis in US adults

“…We note that sepsis mortality rates in African Americans are higher than in the overall population [41]. We also note that temperature may influence bacterial growth rates and/or transmission mediated effects [42], which in turn may affect both the prevalence of antibiotic resistance [42,43], and the acquisition/severity of bacterial infections. To adjust for additional factors not accounted for by the covariates used in the model, we include random effects for the ten Health and Human Services (HHS) regions in the US.…”