Elizabeth Temkin1, Noga Fallach2, Jonatan Almagor2, Beryl Primrose Gladstone3, Evelina Tacconelli3, Yehuda Carmeli4. 1. Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. Electronic address: lizt@tlvmc.gov.il. 2. Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel. 3. Division of Infectious Diseases, Department of Internal Medicine 1, German Center for Infection Research, University Hospital Tuebingen, Tuebingen, Germany. 4. Department of Epidemiology and Preventive Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
Abstract
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.
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.
Authors: Alexander Lawandi; Gleice C Leite; Matthew P Cheng; Brigitte Lefebvre; Jean Longtin; Todd C Lee Journal: Antimicrob Agents Chemother Date: 2021-03-18 Impact factor: 5.191
Authors: Adam Belley; Michael D Huband; Kelley A Fedler; Amy A Watters; Robert K Flamm; Stuart Shapiro; Philipp Knechtle Journal: J Clin Microbiol Date: 2019-07-26 Impact factor: 5.948
Authors: Gabriel K Innes; Pranay R Randad; Anton Korinek; Meghan F Davis; Lance B Price; Anthony D So; Christopher D Heaney Journal: Annu Rev Public Health Date: 2020-01-07 Impact factor: 21.981