A team of European researchers estimates that more than 33,000 people in Europe die each year from antibiotic-resistant infections, and that the growing health burden of these infections is similar to that of influenza, tuberculosis, and HIV combined.
The results of the study, which calculated the incidence of five types of infections caused by antibiotic-resistant bacteria in 31 European Union/European Economic Activity (EU/EEA) countries and measured the impact of those infections in number of cases, attributable deaths, and overall health burden, were published yesterday in The Lancet Infectious Diseases. The estimates are based on 2015 data from the European Antimicrobial Resistance Surveillance Network (EARS-Net).
The authors of the study say the findings illustrate the health impact of antibiotic resistance and will inform national efforts to prevent and control drug-resistant infections. In addition, they note, the findings highlight the need for EU/EEA countries to work together to address the rising burden of antibiotic resistance.
"The estimated burden of infections with antibiotic-resistant bacteria in the EU and EEA is substantial compared with that of other infectious diseases, and has increased since 2007," the authors of the study write. "Strategies to prevent and control antibiotic-resistant bacteria require coordination at EU and EEA and global levels."
Deaths, years lost to resistant infections
The study focused on eight species of bacteria frequently isolated from blood or cerebrospinal fluid and reported to EARS-Net, with 16 resistance patterns. Among the included antibiotic resistance-bacterium combinations were colistin-resistant, carbapenem-resistant, or third-generation cephalosporin-resistant Escherichia coli and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant Enterococcus faecalis and Enterococcus faecium. The five types of infections were bloodstream infections (BSIs), urinary tract infections, respiratory tract infections, surgical site infections, and other infections.
Using EARS-Net data collected from all of 2015, researchers from the European Centre for Disease Prevention and Control (ECDC) and the Burden of AMR Collaborative Group estimated the incidence of infections caused by the selected antibiotic-resistant pathogens in each of the 31 EU/EEA countries, then developed disease outcome models for the five types of infections based on systematic reviews of literature.
Computational models calculated the annual number of cases and incidence rate, the number of attributable deaths and attributable mortality rate, and the number and rate of disability-adjusted life-years (DALYs)—a measure of the number of years lost due to ill-health, disability, or early death.
Based on the EARS-Net data, the researchers estimated that 671,689 infections were caused by the selected antibiotic-resistant bacteria in the EU and EEA in 2015, with 33,110 attributable deaths and 874,541 total DALYs. These estimates corresponded to an incidence rate of 131 infections per 100,000 population, an attributable mortality rate of 6.44 deaths per 100,000 population, and 170 DALYs per 100,000 population. By comparison, influenza, tuberculosis, and HIV combined account for 183 DALYs per 100,000 population.
The burden of antibiotic-resistant infections was highest among children under the age of 1 and adults over the age of 65.
Four drug-resistant pathogens—third-generation cephalosporin-resistant E coli, MRSA, carbapenem-resistant Pseudomonas aeruginosa, and third-generation cephalosporin-resistant K pneumoniae—had the largest impact on health, accounting for 67.9% of the DALYs per 100,000 population. Infections caused by colistin-resistant and carbapenem-resistant bacteria accounted for 38.7% of total DALYs.
Nearly two third of the infections (426,277, 63.5%) were associated with healthcare and accounted for 72.4% of attributable deaths and 74.9% of DALYs. This finding, the authors write, emphasizes "the need to urgently address antimicrobial resistance as a patient safety issue and the need for alternative treatment options for patients with such infections who have co-morbidities or are otherwise vulnerable."
The estimates also revealed that the burden of antibiotic-resistant bacteria is focused on countries in southern and eastern Europe, where antibiotic consumption tends to be higher. Italy and Greece were the most affected countries, accounting for a combined 21.3% of total DALYs. Nearly a third of the deaths caused by antibiotic-resistant bacteria in EU/EEA countries occurred in Italy, while Greece had the highest proportion of DALYs caused by carbapenem-resistant or colistin-resistant bacteria.
When the researchers applied the same method to EARS-Net data from 2007, they found that the median number of deaths attributable to antibiotic-resistant bacteria has more than doubled, rising from 11,144 in 2007 to 27,249 in 2015. The numbers of deaths attributable to carbapenem-resistant K pneumoniae and E coli rose by factors of 6.16 and 4.12, respectively.
Calls for a more centralized approach
The authors say the study is the first to estimate the burden of all types of infections with antibiotic-resistant bacteria and express it in DALYs. Although the methodology is different, the US Centers for Disease Control and Prevention (CDC) produced a similar report in 2013 that used 2011 surveillance to provide estimates of the health burden of antibiotic resistance in the United States.
That report found that antibiotic-resistant infections sickened more than 2 million people a year, with 23,000 attributable deaths.
The researchers note that the incidence of antibiotic-resistant infections in their study is 2.6 times higher than in the CDC study, and attributable mortality is 1.22 times higher.
In a commentary that accompanies the study, Evelina Tacconelli, MD, PhD, and Maria Pezzani, MD, of the University of Verona called the estimates "shocking" and said the results demand greater political commitment and dedicated resources for combating drug-resistant infections. "Tackling antimicrobial resistance is not a simple task and various international stakeholders have been working for many years to reduce this public health burden," they write. "Clearly it is not enough."
Echoing the study authors, Tacconelli and Pezzani argue that solving the problem will likely require "a more centralized global approach" led by the European Parliament. They suggest this approach could include defining continent-wide standards for antibiotic usage in hospitals and the community, establishing a rate of resistance for specific antibiotics at which countries would have to take urgent action, and setting a minimum gold standard for infection control measures. They also recommend that national antimicrobial resistance plans have annual targets.
"This approach follows the example of what has been used from the European Parliament to successfully fight air pollution and reduce the related public health burden," they write. "If Member States can set gold standards for air composition, surely they can agree on gold standards for the prevention and treatment of infections due to resistant bacteria."
Nov 5 Lancet Infect Dis study
Nov 5 Lancet Infect Dis comment
Nov 6 ECDC news release on the study