The burden of antimicrobial resistance in the Americas in 2019: a cross-country systematic analysis

Abstract

Background: Antimicrobial resistance (AMR) is an urgent global health challenge and a critical threat to modern health care. Quantifying its burden in the WHO Region of the Americas has been elusive-despite the region's long history of resistance surveillance. This study provides comprehensive estimates of AMR burden in the Americas to assess this growing health threat.

Methods: We estimated deaths and disability-adjusted life-years (DALYs) attributable to and associated with AMR for 23 bacterial pathogens and 88 pathogen-drug combinations for countries in the WHO Region of the Americas in 2019. We obtained data from mortality registries, surveillance systems, hospital systems, systematic literature reviews, and other sources, and applied predictive statistical modelling to produce estimates of AMR burden for all countries in the Americas. Five broad components were the backbone of our approach: the number of deaths where infection had a role, the proportion of infectious deaths attributable to a given infectious syndrome, the proportion of infectious syndrome deaths attributable to a given pathogen, the percentage of pathogens resistant to an antibiotic class, and the excess risk of mortality (or duration of an infection) associated with this resistance. We then used these components to estimate the disease burden by applying two counterfactual scenarios: deaths attributable to AMR (compared to an alternative scenario where resistant infections are replaced with susceptible ones), and deaths associated with AMR (compared to an alternative scenario where resistant infections would not occur at all). We generated 95% uncertainty intervals (UIs) for final estimates as the 25th and 975th ordered values across 1000 posterior draws, and models were cross-validated for out-of-sample predictive validity.

Findings: We estimated 569,000 deaths (95% UI 406,000-771,000) associated with bacterial AMR and 141,000 deaths (99,900-196,000) attributable to bacterial AMR among the 35 countries in the WHO Region of the Americas in 2019. Lower respiratory and thorax infections, as a syndrome, were responsible for the largest fatal burden of AMR in the region, with 189,000 deaths (149,000-241,000) associated with resistance, followed by bloodstream infections (169,000 deaths [94,200-278,000]) and peritoneal/intra-abdominal infections (118,000 deaths [78,600-168,000]). The six leading pathogens (by order of number of deaths associated with resistance) were Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii. Together, these pathogens were responsible for 452,000 deaths (326,000-608,000) associated with AMR. Methicillin-resistant S. aureus predominated as the leading pathogen-drug combination in 34 countries for deaths attributable to AMR, while aminopenicillin-resistant E. coli was the leading pathogen-drug combination in 15 countries for deaths associated with AMR.

Interpretation: Given the burden across different countries, infectious syndromes, and pathogen-drug combinations, AMR represents a substantial health threat in the Americas. Countries with low access to antibiotics and basic health-care services often face the largest age-standardised mortality rates associated with and attributable to AMR in the region, implicating specific policy interventions. Evidence from this study can guide mitigation efforts that are tailored to the needs of each country in the region while informing decisions regarding funding and resource allocation. Multisectoral and joint cooperative efforts among countries will be a key to success in tackling AMR in the Americas.

Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund.

Keywords: AMR; Americas; Antimicrobial resistance; Bacteria; Disease burden; Mortality.

Fig. 1

Heatmap representing deaths associated with bacterial antimicrobial resistance by pathogen–drug combination in the WHO Region of the Americas, 2019. Values are rounded to three significant figures. Results for Salmonella enterica serovar Paratyphi excluded from this figure due to no appreciable AMR burden for this pathogen in the Region of the Americas (see Table 2). 3GC = third-generation cephalosporins; 4GC = fourth-generation cephalosporins; Anti-pseudomonal = anti-pseudomonal penicillins with or without β-lactamase inhibitors; BL-BLI = β-lactams with β-lactamase inhibitors; Group A Streptococcus = Streptococcus pyogenes; Group B Streptococcus = Streptococcus agalactiae; MDR = multidrug resistance; Mono INH = isoniazid mono-resistance; Mono RIF = rifampicin mono-resistance; Resistance to 1+ = resistance to one or more drugs; S Typhi = S. enterica serovar Typhi; TB = tuberculosis, TMP-SMX = trimethoprim-sulfamethoxazole; XDR = extensive drug resistance.

Fig. 2

Heatmap representing deaths attributable to bacterial antimicrobial resistance by pathogen-drug combination in the WHO Region of the Americas, 2019. Values are rounded to three significant figures. Results for Salmonella enterica serovar Paratyphi excluded from this figure due to no appreciable AMR burden for this pathogen in the Region of the Americas (see Table 2). 3GC = third-generation cephalosporins; 4GC = fourth-generation cephalosporins; Anti-pseudomonal = anti-pseudomonal penicillins with or without β-lactamase inhibitors; BL-BLI = β-lactams with β-lactamase inhibitors; Group A Streptococcus = Streptococcus pyogenes; Group B Streptococcus = Streptococcus agalactiae; MDR = multidrug resistance; Mono INH = isoniazid mono-resistance; Mono RIF = rifampicin mono-resistance; Resistance to 1+ = resistance to one or more drugs; S Typhi = S. enterica serovar Typhi; TB = tuberculosis; TMP-SMX = trimethoprim-sulfamethoxazole; XDR = extensive drug resistance.

Fig. 3

Map of age-standardised mortality rates per 100,000 person-years for deaths associated with (A) and attributable to (B) antimicrobial resistance in the WHO Region of the Americas in 2019. For country-specific results presented in a heatmap, please refer to Appendix 1 Figure S4 (attributable burden) and Appendix 1 Figure S5 (associated burden).

Fig. 4

Age–specific mortality rates for deaths attributable to and deaths associated with AMR per country in the WHO Region of the Americas, 2019. Rates for males are shown on the left-hand side of each plot, while rates for females are shown on the right. To improve within-country rate comparisons for countries with lower rates of burden, the X-axis is truncated at 5250. Rates higher than 5250 are represented by bars that extend to the edge of the plot, with the true rate written in white text. Results for the Region of the Americas as a whole (and the six GBD regions contained within) can be found in Appendix 1 Figure S13.

Fig. 5

Age-standardised mortality rate associated with and attributable to AMR in relation to the status of NAPs for the countries in the WHO Region of the Americas. Rates per 100,000 person-years are coloured according to two dimensions NAP status: the highest self-reported government engagement with the NAP between 2018 and 2021 and whether the NAP was published online as reported in surveys or the WHO NAP website. Grey error bars indicate 95% uncertainty intervals. NAP data was acquired from the Global Database for Tracking Antimicrobial Resistance Country Self-Assessment Survey (TrACSS) responses for the years 2018–2021 and the WHO library of AMR NAPs. Estimates were aggregated across drugs, accounting for the co-occurrence of resistance to multiple drugs. Antigua and Barbuda, Dominica, Grenada, Haiti, Saint Kitts and Nevis and Venezuela AMR NAP progress was last reported in the 2018–2019 survey responses. AMR = antimicrobial resistance; NAP = national AMR action plan.