Antibiotic-Resistant Infections Doubled Since 2007 in Europe

More than 33,000 people died from antibiotic-resistant bacterial infections in the European Union and European Economic Area (EU/EEA) during 2015, a study has found. The estimated burden of these infections has doubled since 2007 and was similar to the combined burden of influenza, tuberculosis, and HIV.

Most of the estimated burden was in hospitals and other healthcare settings, suggesting an "urgent need to address antimicrobial resistance as a patient safety issue and the need for alternative treatment options for patients with such infections who have comorbidities or are otherwise vulnerable (eg, because of their poor immune system or age)," the authors explain.

Alessandro Cassini, MD, from the European Centre for Disease Prevention and Control, Solna, Sweden, and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, the Netherlands, and colleagues published their findings online November 5 in The Lancet.

"Strategies to prevent and control antibiotic-resistant bacteria require coordination at EU/EEA and global levels. However, our study showed that the contribution of various antibiotic-resistant bacteria to the overall burden varies greatly between countries, thus highlighting the need for prevention and control strategies tailored to the need of each EU/EEA country," the researchers write.

The investigators estimated the incidence of infections with 16 antibiotic resistance-bacterium combinations from European Antimicrobial Resistance Surveillance Network 2015 data. They used systematic literature reviews to develop disease outcome models for five types of infection and used Monte Carlo simulations on 2400 disease models to provide estimates of disability-adjusted life-years (DALYs).

The researchers estimate there were 671,689 (95% uncertainty interval [UI], 583,148 - 763,966) infections with antibiotic-resistant bacteria in 2015.

Of those, 63.5% were linked to healthcare, causing 72.4% (23,976 of 33,110) of attributable deaths and 74.9% (127 of 180) of DALYs per 100,000 population.

"This finding suggests that the health effects of infections with antibiotic-resistant bacteria predominantly occur in hospitals and other healthcare settings," the researchers write.

Overall, antibiotic-resistant infections were responsible for an estimated 33,110 (95% UI, 28,480 - 38, 430) attributable deaths and 874,541 (95% UI, 768,837 - 989,068) DALYs.

The incidence of antibiotic-resistant infections was 131 (95% UI, 113 - 149) per 100,000 population, with an attributable mortality of 6.44 (95% UI, 5.54 - 7.48) deaths per 100,000 population and 170 (95% UI, 150 - 192) DALYs per 100,000 population.

Four antibiotic-resistant bacteria had the largest effect on health and accounted for 67.9% of DALYs: third-generation cephalosporin-resistant Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Pseudomonas aeruginosa, and third-generation cephalosporin-resistant Klebsiella pneumoniae.

Infections with colistin- or carbapenem-resistant bacteria were responsible for 38.7% (65.9 of 170) of total DALYs per 100,000.

"Despite its relatively low incidence, carbapenem-resistant K. pneumoniae had a high burden of disease because of its high attributable mortality, whereas vancomycin-resistant Enterococcus faecalis and E. faecium (which had a similar incidence to carbapenem-resistant K. pneumoniae) was associated with a low burden of disease," the authors explain.

Infants younger than 1 year experienced the highest burden, followed by those aged 65 years or older.

The estimated burden was substantially higher in Italy and Greece compared with other EU and EEA countries. Carbapenem- or colistin-resistant bacteria were responsible for a larger portion of the total burden in Greece than in Italy.

"Shocking" Results

The results are "shocking", Evelina Tacconelli, MD, PhD, and Maria Diletta Pezzani, Infectious Diseases, Department of Diagnostic and Public Health, University of Verona, Italy, write in an accompanying comment.

"Their study adds to the evidence base on the burden of antimicrobial resistance and could have a crucial role in fighting such resistance on two major levels. First, it represents a good framework to drive improvements in data reporting in surveillance systems and contributes to the many European initiatives to homogenize surveillance systems. Second, by providing for the first time DALY data for countries with a high burden of antimicrobial resistance, this study calls for increased political awareness of, and commitment to, antimicrobial resistance," Tacconelli and Pezzani explain.

"Although the G7 and G20 nations pushed antimicrobial resistance up the global health agenda, in most of the EU and EEA countries, national plans still seem far from having implemented major actions," they add.

Tacconelli and Pezzani say the problem requires a more centralized global approach and that the European Parliament must play a decisive role.

This "could be achieved through different legal mechanisms, such as by clearly defining standards for antibiotic usage in hospitals and community, establishing an alert zone (eg, critical rate of resistance at which urgent actions are needed at the country level) for resistance to specific antibiotics in invasive infections, setting a minimum gold standard for infection control measures to be mandatorily applied, defining curricula for infection control and antibiotic stewardship to be compulsorily included in medical schools, and setting up appropriate indicators to monitor the implementation and effectiveness of interventions," they explain.

"Annual targets in national plans should be globally discussed, interconnected, and coordinated. When countries do not respect agreed targets, action should be taken," they add.

The editorialists point to the success of the European Parliament in fighting air pollution and reducing the related public health burden as evidence that this is possible, saying, "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."

One author has reported receiving consultancy fees from Xellia Pharmaceuticals and Fidelta. One author has reported receiving a grant from the Ministry of Health, Poland, for the National Program for Antibiotic Protection. One author has reported that Landspitali received grants from GlaxoSmithKline Vaccines to study pneumococcal vaccination in Iceland. One author has reported grants from Pfizer and Gilead Sciences, and honoraria from Pfizer, Achaogen, MSD, and Rempex. One author has reported personal fees from Angelini Pharmaceuticals. Tacconelli and Pezzani have reported no relevant financial relationships.

Lancet. Published online November 5, 2018.