Systematic review of wastewater surveillance of antimicrobial resistance in human populations

Abstract

Objectives: We systematically reviewed studies using wastewater for AMR surveillance in human populations, to determine: (i) evidence of concordance between wastewater-human AMR prevalence estimates, and (ii) methodological approaches which optimised identifying such an association, and which could be recommended as standard. We used Lin's concordance correlation coefficient (CCC) to quantify concordance between AMR prevalence estimates in wastewater and human compartments (where CCC = 1 reflects perfect concordance), and logistic regression to identify study features (e.g. sampling methods) associated with high agreement studies (defined as >70% of within-study wastewater-human AMR prevalence comparisons within ±10%).

Results: Of 8,867 records and 441 full-text methods reviewed, 33 studies were included. AMR prevalence data was extractable from 24 studies conducting phenotypic-only (n = 7), genotypic-only (n = 1) or combined (n = 16) AMR detection. Overall concordance of wastewater-human AMR prevalence estimates was reasonably high for both phenotypic (CCC = 0.85 [95% CI 0.8-0.89]) and genotypic approaches (CCC = 0.88 (95% CI 0.84-0.9)) despite diverse study designs, bacterial species investigated and phenotypic/genotypic targets. No significant relationships between methodological approaches and high agreement studies were identified using logistic regression; however, this was limited by inconsistent reporting of study features, significant heterogeneity in approaches and limited sample size. Based on a secondary, descriptive synthesis, studies conducting composite sampling of wastewater influent, longitudinal sampling >12 months, and time-/location-matched sampling of wastewater and human compartments generally had higher agreement.

Conclusion: Wastewater-based surveillance of AMR appears promising, with high overall concordance between wastewater and human AMR prevalence estimates in studies irrespective of heterogenous approaches. However, our review suggests future work would benefit from: time-/location-matched sampling of wastewater and human populations, composite sampling of influent, and sampling >12 months for longitudinal studies. Further research and clear and consistent reporting of study methods is required to identify optimal practice.

Keywords: AMR; Epidemiology; Sewage; Surveillance; Wastewater.

Fig. 1

PRISMA flowchart of search strategy and study inclusion/exclusions.

Fig. 2

Geographic distribution of wastewater sampling and test approach of included studies. Centroids of countries sampled by included studies are plotted with colours and shapes according to citation and antimicrobial susceptibility test (AST) approach respectively. Centroid are plotted with jitter to avoid overplotting and do not represent exact sampling locations within countries.

Fig. 3

AMR in wastewater isolates and human isolates for phenotypic (A) and genotypic (B) comparisons. Left: Concordance plot of AMR prevalence in wastewater and human isolates stratified by AMR detection approach (i.e. phenotypic (A) versus genotypic (B) approaches). Each point represents a single wastewater-human comparison conducted where colour corresponds to bacterial species tested and shape corresponds to human sample type used. Lin’s concordance correlation coefficient (CCC) is labelled with 95% confidence intervals. Unbroken line of y = x is plotted as perfect concordance between wastewater and human resistance. Dashed lines of y = x + 0.1 and y = x-0.1 represent high concordance, i.e. ±10% from perfect concordance respectively. Right: Individual wastewater-human comparisons tallied by level of discordance (<5% and 5–10% coloured in green, 15–20% and >20% coloured in purple) between compared wastewater and human AMR prevalence estimates, and plotted to show number of comparisons at each level of discordance, stratified by the target species and antibiotic class (3A-right) or AMR gene family (3B-right).