Sims Natalie, Kannan Andrew, Holton Elizabeth, Jagadeesan Kishore, Mageiros Leonardos, Standerwick Richard, Craft Tim, Barden Ruth, Feil Edward J, Kasprzyk-Hordern Barbara
University of Bath, Department of Chemistry, Bath, BA2 7AY, UK; Centre for Sustainable Circular Technologies, Bath, BA2 7AY, UK.
University of Bath, Department of Chemistry, Bath, BA2 7AY, UK.
Environ Pollut. 2023 Sep 15;333:122020. doi: 10.1016/j.envpol.2023.122020. Epub 2023 Jun 17.
This longitudinal study tests correlations between antimicrobial agents (AA) and corresponding antimicrobial resistance genes (ARGs) generated by a community of >100 k people inhabiting one city (Bath) over a 13 month randomised monitoring programme of community wastewater. Several AAs experienced seasonal fluctuations, such as the macrolides erythromycin and clarithromycin that were found in higher loads in winter, whilst other AA levels, including sulfamethoxazole and sulfapyridine, stayed consistent over the study period. Interestingly, and as opposed to AAs, ARGs prevalence was found to be less variable, which indicates that fluctuations in AA usage might either not directly affect ARG levels or this process spans beyond the 13-month monitoring period. However, it is important to note that weekly positive correlations between individual associated AAs and ARGs were observed where seasonal variability in AA use was reported: ermB and macrolides CLR-clarithromycin and dmCLR-N-desmethyl clarithromycin, aSPY- N-acetyl sulfapyridine and sul1, and OFX-ofloxacin and qnrS. Furthermore, ARG loads normalised to 16S rRNA (gene load per microorganism) were positively correlated to the ARG loads normalised to the human population (gene load per capita), which indicates that the abundance of microorganisms is proportional to the size of human population and that the community size, and not AA levels, is a major driver of ARG levels in wastewater. Comparison of hospital and community wastewater showed higher number of AAs and their metabolites, their frequency of occurrence and concentrations in hospital wastewater. Examples include: LZD-linezolid (used only in severe bacterial infections) and AMX-amoxicillin (widely used, also in community but with very low wastewater stability) that were found only in hospital wastewater. CIP-ciprofloxacin, SMX-sulfamethoxazole, TMP-trimethoprim, MTZ-metronidazole and macrolides were found at much higher concentrations in hospital wastewater while TET-tetracycline and OTC-oxytetracycline, as well as antiretrovirals, had an opposite trend. In contrast, comparable concentrations of resistant genes were observed in both community and hospital wastewater. This supports the hypothesis that AMR levels are more of an endemic nature, developing over time in individual communities. Both hospital and community wastewater had AAs that exceeded PNEC values (e.g. CLR-clarithromycin, CIP-ciprofloxacin). In general, though, hospital effluents had a greater number of quantifiable AAs exceeding PNECs (e.g. SMX-sulfamethoxazole, ERY-erythromycin, TMP-trimethoprim). Hospitals are therefore an important consideration in AMR surveillance as could be high risk areas for AMR.
这项纵向研究测试了在一项为期13个月的社区废水随机监测计划中，居住在一个城市（巴斯）的10万多人的社区产生的抗菌剂（AA）与相应抗菌抗性基因（ARG）之间的相关性。几种抗菌剂经历了季节性波动，例如大环内酯类的红霉素和克拉霉素在冬季的负荷量更高，而其他抗菌剂水平，包括磺胺甲恶唑和磺胺吡啶，在研究期间保持稳定。有趣的是，与抗菌剂相反，抗菌抗性基因的流行率变化较小，这表明抗菌剂使用的波动可能不会直接影响抗菌抗性基因水平，或者这个过程跨越了13个月的监测期。然而，需要注意的是，在报告了抗菌剂使用季节性变化的情况下，观察到个别相关抗菌剂与抗菌抗性基因之间存在每周正相关：ermB与大环内酯类的CLR-克拉霉素和dmCLR-N-去甲基克拉霉素、aSPY-N-乙酰磺胺吡啶和sul1，以及OFX-氧氟沙星和qnrS。此外，归一化至16S rRNA的抗菌抗性基因负荷（每微生物的基因负荷）与归一化至人口的抗菌抗性基因负荷（人均基因负荷）呈正相关，这表明微生物的丰度与人口规模成正比，并且社区规模而非抗菌剂水平是废水中抗菌抗性基因水平的主要驱动因素。医院废水和社区废水的比较显示，医院废水中抗菌剂及其代谢物的数量、出现频率和浓度更高。例如：LZD-利奈唑胺（仅用于严重细菌感染）和AMX-阿莫西林（广泛使用，社区中也有，但在废水中稳定性极低）仅在医院废水中被发现。环丙沙星、磺胺甲恶唑、甲氧苄啶、甲硝唑和大环内酯类在医院废水中的浓度要高得多，而四环素和土霉素以及抗逆转录病毒药物则呈现相反的趋势。相比之下，在社区废水和医院废水中观察到的抗性基因浓度相当。这支持了抗菌药物耐药性水平更具地方性的假设，即在各个社区中随时间发展。医院废水和社区废水都有超过预测无效应浓度（PNEC）值的抗菌剂（例如CLR-克拉霉素、CIP-环丙沙星）。不过总体而言，医院污水中超过PNECs的可量化抗菌剂数量更多（例如SMX-磺胺甲恶唑、ERY-红霉素、TMP-甲氧苄啶）。因此，医院是抗菌药物耐药性监测的重要考虑因素，因为可能是抗菌药物耐药性的高风险区域。
