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Background  With inappropriate use of antimicrobials becoming a great public health concern globally, the issue of applying clinical practice guidelines (CPGs) to regulate the rational use of antimicrobials has attracted increasing attention. Taking tertiary general hospitals in China for example, this study aimed to identify factors to investigate the comprehensive influencing mechanism for physicians’ intention to use CPGs on antimicrobials.    Methods  Based on the integration of Theory of Planned Behavior (TPB), Technology Acceptance Model (TAM), and Technology-Organization-Environment framework (TOE), a questionnaire survey was conducted covering potential determinants of affecting physicians’ intentions to use CPGs on antimicrobials at the individual level (attitude, subjective norms and perceived risk), technical level (relative advantage and ease of use), and organizational level (top management support and organizational implementation). Data were collected from 644 physicians in tertiary general hospitals in eastern, central and western China, which were obtained by multi-stage random sampling. The structural equation modeling (SEM) was used to link three-level factors with physicians’ behavioral intentions.    Results  The majority of the participants (94.57%) showed a positive tendency toward intention to use CPGs on antimicrobials. The reliability and validity analysis showed the questionnaire developed from the theoretical model was acceptable. SEM results revealed physicians’ intentions to use CPGs on antimicrobials was associated with attitude ( β  = 0.166,  p  < 0.05), subjective norms ( β  = 0.244,  p  < 0.05), perceived risk ( β  = − 0.113,  p  < 0.05), relative advantage ( β  = 0.307,  p  < 0.01), top management support ( β  = 0.200,  p  < 0.05) and organizational implementation ( β  = 0.176,  p  < 0.05). Besides, subjective norms, perceived risk, relative advantage, ease of use, and top management support showed their mediating effects from large to small on the intentions, which were 0.215, 0.140, 0.103, 0.088, − 0.020, respectively.    Conclusions  This study revealed the significance of multifaceted factors to enhance the intention to use CPGs on antimicrobials. These findings will not only contribute to the development of targeted intervention strategies on promoting the use of CPGs on antimicrobials, but also provide insights for future studies about physicians’ adoption behaviors on certain health services or products.    Supplementary information  The online version contains supplementary material available at 10.1186/s13756-021-00966-z.

antimicrobial resistance and infection control

Predictors of physicians’ intentions to use clinical practice guidelines on antimicrobial in tertiary general hospitals of China: a structural equation modeling approach