Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, Davis, CA, USA.
Veterinary Medicine Teaching and Research Center, University of California Davis, Tulare, CA, USA.
Sci Rep. 2024 Feb 23;14(1):4448. doi: 10.1038/s41598-024-54738-x.
The objective of this study was to evaluate the impact of dietary zinc supplementation in pre-weaned dairy calves on the phenotypic antimicrobial resistance (AMR) of fecal commensal bacteria. A repository of fecal specimens from a random sample of calves block-randomized into placebo (n = 39) and zinc sulfate (n = 28) groups collected over a zinc supplementation clinical trial at the onset of calf diarrhea, calf diarrheal cure, and the last day of 14 cumulative days of zinc or placebo treatment were analyzed. Antimicrobial susceptibility testing was conducted for Enterococcus spp. (n = 167) and E. coli (n = 44), with one representative isolate of each commensal bacteria tested per sample. Parametric survival interval regression models were constructed to evaluate the association between zinc treatment and phenotypic AMR, with exponentiated accelerated failure time (AFT) coefficients adapted for MIC instead of time representing the degree of change in AMR (MIC Ratio, MR). Findings from our study indicated that zinc supplementation did not significantly alter the MIC in Enterococcus spp. for 13 drugs: gentamicin, vancomycin, ciprofloxacin, erythromycin, penicillin, nitrofurantoin, linezolid, quinupristin/dalfopristin, tylosin tartrate, streptomycin, daptomycin, chloramphenicol, and tigecycline (MR = 0.96-2.94, p > 0.05). In E. coli, zinc supplementation was not associated with resistance to azithromycin (MR = 0.80, p > 0.05) and ceftriaxone (MR = 0.95, p > 0.05). However, a significant reduction in E. coli MIC values was observed for ciprofloxacin (MR = 0.17, 95% CI 0.03-0.97) and nalidixic acid (MR = 0.28, 95% CI 0.15-0.53) for zinc-treated compared to placebo-treated calves. Alongside predictions of MIC values generated from these 17 AFT models, findings from this study corroborate the influence of age and antimicrobial exposure on phenotypic AMR.
本研究旨在评估在哺乳期奶牛中补充锌对粪便共生菌表型抗微生物药物耐药性（AMR）的影响。本研究对一项锌补充临床试验中随机分组的安慰剂（n=39）和硫酸锌（n=28）组小牛粪便样本库进行了分析，这些样本是在小牛腹泻发作时、小牛腹泻治愈时和 14 天累积锌或安慰剂治疗的最后一天收集的。对粪肠球菌（n=167）和大肠杆菌（n=44）进行了抗微生物药物敏感性测试，每个样本测试了一种共生菌的一个代表性分离株。构建了参数生存间隔回归模型，以评估锌处理与表型 AMR 之间的关联，用 MIC 而不是时间表示 AMR 变化程度的指数加速失效时间（AFT）系数（MIC 比值，MR）。本研究结果表明，锌补充剂对 13 种药物的粪肠球菌 MIC 没有显著影响：庆大霉素、万古霉素、环丙沙星、红霉素、青霉素、呋喃妥因、利奈唑胺、奎奴普丁/达福普汀、替考拉宁、链霉素、达托霉素、氯霉素和替加环素（MR=0.96-2.94，p>0.05）。在大肠杆菌中，锌补充剂与阿奇霉素（MR=0.80，p>0.05）和头孢曲松（MR=0.95，p>0.05）耐药性无关。然而，与安慰剂治疗的小牛相比，锌治疗的小牛中发现环丙沙星（MR=0.17，95%CI 0.03-0.97）和萘啶酸（MR=0.28，95%CI 0.15-0.53）的大肠杆菌 MIC 值显著降低。除了这些 17 个 AFT 模型生成的 MIC 值预测外，本研究结果还证实了年龄和抗微生物药物暴露对表型 AMR 的影响。
