Background: The number of infections caused by resistant organisms is largely unknown. We estimated the number of infections worldwide that are caused by the WHO priority pathogens third-generation cephalosporin-resistant and carbapenem-resistant Escherichia coli and Klebsiella pneumoniae.

Methods: We calculated a uniform weighted mean incidence of serious infections caused by antibiotic-susceptible E coli and K pneumoniae using data from 17 countries. Using this uniform incidence, as well as population sizes and country-specific resistance levels, we estimated the number of infections caused by third-generation cephalosporin-resistant and carbapenem-resistant E coli and K pneumoniae in 193 countries in 2014. We also calculated interval estimates derived from changing the fixed incidence of susceptible infections to 1 SD below and above the weighted mean. We compared an additive model with combination models in which resistant infections were replaced by susceptible infections. We distinguished between higher-certainty regions (those with good-quality data sources for resistance levels and resistance ≤30%), moderate-certainty regions (those with good-quality data sources for resistance levels and including some countries with resistance >30%), and low-certainty regions (those in which good-quality data sources for resistance levels were unavailable for countries comprising at least 20% of the region's population, regardless of resistance level).

Findings: Using the additive model, we estimated that third-generation cephalosporin-resistant E coli and K pneumoniae caused 6·4 million (interval estimate 3·5-9·2) bloodstream infections and 50·1 million (27·5-72·8) serious infections in 2014; estimates were 5·5 million (3·0-7·9) bloodstream infections and 43·1 million (23·6-62·2) serious infections in the 25% replacement model, 4·6 million (2·5-6·6) bloodstream infections and 36·0 million (19·7-52·2) serious infections in the 50% replacement model, and 3·7 million (2·0-5·3) bloodstream infections and 28·9 million (15·8-41·9) serious infections in the 75% replacement model. Carbapenem-resistant strains caused 0·5 million (0·3-0·7) bloodstream infections and 3·1 million (1·8-4·5) serious infections based on the additive model, 0·5 million (0·3-0·7) bloodstream infections and 3·0 million (1·7-4·3) serious infections based on the 25% replacement model, 0·4 million (0·2-0·6) bloodstream infections and 2·8 million (1·6-4·1) serious infections based on the 50% replacement model, and 0·4 million (0·2-0·6) bloodstream infections and 2·7 million (1·5-3·8) serious infections based on the 75% replacement model.

Interpretation: To our knowledge, this study is the first to report estimates of the global number of infections caused by antibiotic-resistant priority pathogens. Uncertainty stems from scant data on resistance levels from low-income and middle-income countries and insufficient knowledge regarding resistance dynamics when resistance is high.

Funding: Innovative Medicines Initiative.