Temporal association of antimicrobial use in livestock with antimicrobial resistance in non-typhoid Salmonella human infections in the Netherlands, 2008–2019

Background: Antimicrobial use (AMU) in livestock contributes to antimicrobial resistance (AMR) among zoonotic pathogens, such as non-typhoid Salmonella (NTS). Since 2009, the Netherlands has made substantial efforts to reduce AMU in livestock. Objectives: To assess the association between AMU in livestock and AMR in NTS human isolates. Additionally, associations between AMU in broilers/pigs and AMR in NTS broiler/pig isolates, and between AMR in broilers/pigs and in human NTS isolates were assessed. The focus was on Salmonella Enteritidis (SE) and Salmonella Typhimurium including its monophasic variant (ST/STM). Methods: A national population registry-based study was conducted in the Netherlands from 2008 to 2019. Multivariable logistic regression models were used to assess the associations between livestock AMU and NTS resistance proportion in humans and broilers/pigs, overall as well as per class-specific antimicrobials. Correlation analysis was performed to relate AMR proportions between human and broiler/pig NTS isolates. Results: For SE, only a positive association between penicillins use in broilers and resistance to ampicillin among human isolates was significant. For ST/STM, most associations between AMU in livestock and AMR among human isolates were significantly positive, overall and per class-specific antimicrobials, namely for penicillins-ampicillin, tetracyclines-tetracycline and sulfonamides/trimethoprim-sulfamethoxazole/trimethoprim. Significantly positive associations between AMU in broilers/pigs and AMR in broiler/pig ST/STM isolates were also observed, but not between broiler/pig and human AMR levels. Conclusions: Significant associations were generally found between livestock AMU and AMR in human and broiler/pig ST/STM isolates. However, confounding factors, such as imported meat and travel are of concern. To fully comprehend the impact of livestock AMU on resistance in human NTS isolates, it is imperative to enhance AMR surveillance of NTS.