## 5 Conclusions and Recommendations  
The present study aimed to appraise all relevant literature for the presence of pharmaceuticals responsible for the development of antimicrobial resistance in wastewater and to provide detailed and updated information valuable for the management of AMR dissemination in wastewater treatment plants. The review of 18 studies covered 25 countries; 21 are European. Therefore, it can be asserted that notwithstanding that the discharge of harmful antimicrobials is a widespread global issue, research is of particular significance to Europe. Here, a list of the seven most concerning pharmaceuticals commonly found in the influents and effluents of wastewater treatment plants is proposed. Ciprofloxacin, clarithromycin, erythromycin, metronidazolezole, ofloxacin, sulfamethoxazole and trimethoprim constitute a considerable risk in terms of ubiquitous distribution, worrying concentrations and RQ values and capacities to resist removal treatments. Especially concerning were the PRs ciprofloxacin, clarithromycin and ofloxacin as these were frequently detected at levels above the predicted no-effect concentrations for resistance selection, which make these compounds the most concerning antimicrobials that encourage the development of antimicrobial resistance. In conclusion, based on the gaps in knowledge identified during this systematic review, the main recommendations are as follows:  
* The reliability of study outcomes must be improved through the implementation of standardised guidelines for the suitable selection of analytical procedures, data representation, and statistical analysis. The experiments should not be based on daily campaigns composing of a singular grab sample, but instead, values for concentrations should be the result of the mean of at least three replicates. * The need remains for time-weighted screenings to capture seasonal variations in both the influent levels of pharmaceuticals and the effluent levels discharged into aquatic matrices to better assess the impact of wastewater treatment plants on the environment. * The necessity of studies dealing specifically with the presence of antimicrobial substances in hospital wastewater or correlating the removal efficiencies of wastewater treatment plants with treatments used is stressed. * Call for awareness about the problem of pharmaceuticals compounds in wastewater and the related spread of antimicrobial resistance: the research in this field needs to be expanded to a global level. The following are available online at [[https://www.mdpi.com/article/10.3390/app11156670/s1](https://www.mdpi.com/article/10.3390/app11156670/s1)]([https://www.mdpi.com/article/10.3390/app11156670/s1](https://www.mdpi.com/article/10.3390/app11156670/s1)). **Tables.doc: Table S1**: Pre-set list of exclusion and inclusion criteria for the title and abstract screening phases. **Table S2**: Pre-set list of characteristics and results that were coded and extracted from each study. **Table S3**: Strings designed for each database. **Tables S4-S7**: One-way ANOVA results on the seasonal differences in ofloxacin and sulfamethoxazole concentrations in influent WW. **Tables S8-S11**: One-way ANOVA and independent \(t\)-test results on the seasonal differences in azithromycin and ciprofloxacin concentrations in effluent. **Tables S12-S18**: Independent \(t\)-test results on the seasonal differences in sulfadiazine and tetracycline concentrations in influent and effluent hospital and municipal WWTPs. **Data_extraction.slx**: Risk of bias, Influents, Effluents, Removals, Risk Assessment and PRs list. References [53-59] refer to the supplementary material. Conceptualisation, G.F.; methodology, G.F.; software, G.F.; validation, G.F., D.R., J.R., C.H., A.E. and K.H. ; formal analysis, G.F.; investigation, G.F. and D.R. ; resources, G.F.; data curation, G.F. and D.R. ; writing--original draft preparation, G.F. and D.R. ; writing--review and editing, J.R., C.H., A.E. and K.H. ; visualisation, G.F.; supervision, J.R., J.S., C.H. and A.E.