Mortality and genetic diversity of antibiotic-resistant bacteria associated with bloodstream infections: a systemic review and genomic analysis

Abstract

Abstract Background Bloodstream infections (BSIs) caused by antibiotic-resistant bacteria (ARB) represent a significant disease burden worldwide. However, a comprehensive analysis of the mortality rates and global epidemiology across different ARB species associated with BSIs is currently lacking. Methods We conducted a systematic review by searching multiple databases (PubMed, Web of Science, and Embase) for studies reporting ARB-related BSIs data up to June 19, 2023. Additionally, we performed genomic analyses of all the publicly available bacterial genomes associated with BSIs to elucidate their molecular characteristics. Results A total of 322 articles (N = 90,672 patients) were included in this study. For 28 or 30-day mortality, the overall mortality rate for all ARB species was 32.0%. Among them, antibiotic-resistant A. baumannii exhibited the highest rate (54.2%). And the top three ARB types with the highest mortality rates at 28 or 30-day were CefeR-PA (cefepime-resistant P. aeruginosa), CREC (carbapenem-resistant E. coli), and CRAB (carbapenem-resistant A. baumannii), all exceeding 50%, whereas the mortality rates of CRKP (carbapenem-resistant K. pneumoniae), CRPA (carbapenem-resistant P. aeruginosa), and VREfm (vancomycin-resistant E. faecium) were at least 40%. A total of 9,289 ARB genomes related to BSIs were acquired from the NPDIB database and are predominantly distributed in North America, Asia, and Europe. Antibiotic resistance gene (ARG) analysis identified a total of 613 ARG subtypes from the top six ARB species, with numbers ranging from 48 for E. faecium to 253 for K. pneumoniae. Furthermore, specific clones of ARB species were strongly associated with BSIs, such as ST131 in E. coli, ST8, and ST5 in S. aureus, ST2 in A. baumannii, and ST11 and ST258 in K. pneumoniae. Conclusion ARB contributed to the burden of BSIs, with a 30-day all-cause mortality rate as high as 32.0%. ARB strains causing BSIs display high genetic diversity, highlighting the importance of continuing to monitor high-risk clones to control the development of antibiotic resistance. Differences in ARGs patterns require tailored antibiotic management strategies for each ARB species.

Keywords

• Bloodstream infections
• Bacterial resistance
• Mortality
• Genomic epidemiology