Background To estimate the global trends and disease burden of Clostridioides difficile infection (CDI) and its correlation with worldwide antibiotic consumption. Methods Clostridioides difficile infection and antibiotic consumption data were retrieved from the Global Burden of Disease 2019, ResistanceMap-AntibiocUse, Food and Drug Administration (FDA) Adverse Event Reporting System, and Global Antimicrobial Resistance and Use Surveillance System. Jointpoint regression and age-period-cohort model were developed to show the global trends and burden of CDI. Correlation tests were calculated to explore the relationship between CDI and antibiotics. Results Globally, CDI is the most significant one with a high-rocketing burden increase rate among 13 pathogens causing diarrheal deaths and disability-adjusted life years (DALYs). The age-standardised death rate (ASDR) increased from 0.19 in 1990 to 0.43 in 2019, in which the elderly and females are at higher risk. A rapid increase in ASDR in high to middle sociodemographic index (SDI) regions such as North America (average annual percentage change (AAPC) = 7.71%), Andean (AAPC = 7.82%), and Southern Latin America (AAPC = 11.08%) was identified. Antibiotic consumption has a significant positive correlation with CDI with different risk stratifications. Conclusions The global burden of CDI has continuously increased for the past 30 years, especially in high to middle-SDI regions. World antibiotic consumption showed a strong positive correlation with CDI with different risk stratification. More effective prevention and control measures should be implemented in these critical regions, with a specific emphasis on vulnerable populations, to mitigate the spread of epidemics.
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