Table 1.

Overview of the studies included in this systematic review. AMR: antimicrobial resistant, ARG: antimicrobial resistant genes, ARB: antimicrobial resistant bacteria and MGE: mobile genetic elements.

No.	References	Source of Samples	Types of Investigated Samples	Key Findings
1	Nahar et al., 2019 [ 35 ]	Sewage and environmental water	Sewage, river, pond and swimming pool water	AMR bacteria of E. coli and Salmonella spp. were detected in all environmental samples.
2	Qin et al., 2019 [ 36 ]	Sewage	Hospital sewage	Novel species (Acinetobacter cumulans) containing ARGs conferring resistance to carbapenems, cephalosporin or aminoglycoside were identified.
3	Haberecht et al., 2019 [ 37 ]	Sewage and environmental waters	Sewage water, wastewater treatment plant (WWTP) (influent and effluent) and surface water (ambient water)	Increased abundance of ARB and multidrug resistant (MDR) strains were detected in influent compared to effluent wastewater. Extended-spectrum β-lactamases (ESBL)-producing E. coli strains have been identified in environmental surface water.
4	Sekizuka et al., 2018 [ 38 ]	Sewage	WWTP effluent	Carbapenem-producing strain of K. pneumonia carrying blaKPC-2 was detected. This novel resistant strain rarely detected in clinical settings in Japan.
5	Cahill et al., 2019 [ 39 ]	Sewage and environmental wastewater	Hospital and municipal wastewater (pre- and post-hospital)	Higher rates of carbapenemase-producing Enterobacteriaceae (CPE) have been detected in hospital effluent.
6	Niestepski et al., 2019 [ 40 ]	Sewage, environmental water and human faeces	Hospital wastewater, WWTP (influent and effluent) and human faeces	The highest drug-resistance levels were observed in the strains isolated from influent and effluent WWTP water. Bacteria of Bacteroides fragilis group (BFG) isolated from the WWTPs characterised by higher resistant profiles than those that have been recovered from human and rat faeces.
7	Hendrieksen et al., 2019 [ 41 ]	Sewage	Domestic sewage	Clinically relevant ARGs associated with resistance to macrolides, tetracycline, aminoglycoside, beta-lactams and sulfonamides were identified. The abundance of ARGs were higher in samples collected from low-income compared to high-income countries.
8	Khan et al., 2019 [ 42 ]	Sewage and environmental waters	Hospital wastewater, WWTP samples and downstream water	β-lactamase genes, including blaIMP−1, blaIMP−2 and blaOXA−23, were detected only in hospital sewage, while blaOXA−48, blaCTX−M−8 and blaSFC−1, blaVIM−1 and blaVIM−13 were only detected in downstream river water but not in the WWTP.
9	Tokajian et al., 2018 [ 43 ]	Sewage and environmental waters	Refugee camp sewage water and rivers effluent	Higher rates of AMR E. coli isolates, including ESBL-producing strains, and those which showed resistance to different antimicrobial drugs, including aminoglycosides, fluoroquinolones and trimethoprim/sulfamethosazole, were detected in samples from refugee camps.
10	Parnanen et al., 2019 [ 44 ]	Sewage	Influent and effluent WWTPs samples from different countries	Significantly higher rates of ARGs were identified in effluent samples from low-income compared to high-income countries.
11	Bougnom et al., 2019 [ 45 ]	Sewage	Urban wastewater for agriculture (three canals with different settings)	Higher rates of ARG that confer resistance to 11 major antimicrobial drug groups, including aminoglycoside, tetracycline, beta-lactams and macrolides, were detected in urban wastewater. There was difference in the composition of ARGs associated with ESBL within city water from three canals that received water from different environments, including hospitals.
12	Gouliouris et al., 2019 [ 46 ]	Sewage	Municipal wastewater (untreated and treated) and hospital sewage	Higher rates of vancomycin and ampicillin-resistant E. faecium closely related to hospital isolates have been detected in untreated wastewater plants receiving directly from hospital sewage.
13	Iweriebor et al., 2015 [ 47 ]	Sewage	Municipal and hospital wastewater	Ninety-one percent and 100% of the Enterococcus spp. (E. faecalis and E. durans) isolated from the hospital wastewater and final effluent wastewater, respectively, were resistant to vancomycin and erythromycin.
14	Guo et al., 2017 [ 48 ]	Sewage	Aerobic-activated sludge (AAS) and an aerobically digested sludge (ADS)	Although MGEs, including plasmids; transposons; integrons (e.g., intI1) and insertion sequences (e.g., ISSsp4, ISMsa21 and ISMba16) were abundant in both the activated and digested sludge. However, distinct microbial populations were associated with the two sledge samples.
15	Wang JL, et al., 2015 [ 49 ]	Sewage	Pharmaceutical WTP (all stages of processing)	The abundance of clinically relevant ARGs, including sul1, sul2, tetO, tetT, tetW and tetM, remained consistently higher throughout the processing stages and discharged into the environment.
16	Conte D et al., 2017 [ 50 ]	Sewage and environmental waters	Hospital effluent, sanitary effluent, different sites within WWTP and upstream and downstream river water	ESBL-producing K. pneumonia and E. coli isolates were higher in hospital effluent and WWTP and river samples, respectively. Quinolone-resistant isolates were identified in hospital effluent, sanitary effluent, outflow sewage and surface water samples. MDR bacteria were detected in the hospital effluent and river waters.
17	Baumlisberger et al., 2015 [ 51 ]	Sewage	Up- and downstream wastewater from nursing home	No obvious difference in ARG and MGE abundances were detected between up- and downstream samples.
18	Adefisoye et al., 2016 [ 52 ]	Sewage	Final effluents of WWTP	MDR E coli isolates associated with neonatal meningitis; intestinal (enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC) and enteroaggregative E. coli (EAEC)) and ex-intestinal (UPEC) were identified.
19	Suzuki et al., 2015 [ 53 ]	Sewage and environmental waters	Effluents of WWTP and surface water	High levels of ARGs associated with resistance to sulfamethosazole and oxytetracycline were detected in environmental surface water.
20	Froes AM et al., 2016 [ 54 ]	Sewage	Hospital’s wastewater	Diverse ARGs of serine β-lactamases, including uncommon β lactamase genes blaPER, blaVEB and blaGES, were detected in hospital’s wastewater.
21	Laht M et al., 2014 [ 55 ]	Sewage	WWTP	High levels of ARGs associated with resistance to tetracycline, sulfonamide and β-lactam were detected in all stages in WWTP wastewater. No difference in ARGs abundance was identified after the purification process.
22	Walsh et al., 2011 [ 56 ]	Sewage and environmental water	Seepage water, public tap water and control samples: sewage effluent samples from Wales	blaNDM-1-producing bacteria were isolated from 17% (12 out 171) and 4% (2 out 50) of seepage and tap water samples, respectively. The detected strains included 11 species in which blaNDM-1 had not previously been reported (e.g., Shigella boydii and Vibrio cholerae).
23	Zhang T et al., 2011 [ 57 ]	Sewage	Activated sludge of WWTP	Novel plasmids carrying ARGs associated with tetracycline, aminoglycoside and β-lactam resistance were identified. ARGs associated with resistance to tetracycline, macrolide and MDR were highly enriched in the activated sludge.
24	Chagas TP et al., 2011 [ 58 ]	Sewage	Influent, clarifier tank effluent and chlorine tank effluent from hospital STP (sewage treatment plant)	Multiresistant and ESBL-producing bacteria (high resistant rates to amikacin, trimethoprim/sulphametoxazole and cefalothin) were identified in the chlorine contact tank effluent.
25	Szczepanowski et al., 2009 [ 59 ]	Sewage	Activated sludge samples and final effluent of WWTP	Clinically relevant ARGs associated with resistance to several antimicrobial drugs, including aminoglycoside and β-lactam, were identified in activated sludge and effluent wastewater.
26	Li D et al., 2010 [ 60 ]	Sewage and environmental waste water	Wastewater, river water-up (RWU) and -downstream (RWD) associated with oxytetracycline production WWTP	High concentrations of oxytetracycline were identified in wastewater and in river water downstream but not in upstream waters. MDR phenotypes isolates were identified in the WW and RWD and less frequent in RWU.
27	Zhang H et al., 2019 [ 61 ]	Sewage	Samples from 18 WWTPs	Activated sludge was the main reservoir of ARGs associated with resistance to sulfonamide (sul1 and sul2) and tetracycline (tetW, tetX and tetQ).
28	Li, B et al., 2015 [ 62 ]	Sewage, environmental water and faecal samples	Samples from AAS and ADS and different environmental waters and faecal samples (human, chicken and pig)	High level of ARGs, including those associated with MDR, and resistance to bacitracin; tetracycline; β-lactam; macrolide, lincosamide and streptogramin (MLS); aminoglycoside; quinolone and sulphonamide were detected in all samples.
29	Hembach et al., 2017 [ 63 ]	Sewage	Influent and effluent water from seven WWTPs	mcr-1 (associated with resistance to colistin) was detected in influent samples of all seven WWTPs and some of effluent waters (i.e., it was not eliminated during wastewater treatment reaching the aquatic environment). AMR strains of A. baumannii, E. coli and K. pneumonia were detected in both influent and effluents samples.
30	Igbinosa IH et al., 2012 [ 64 ]	Sewage	WWTP	AMR Aeromonas spp. isolates resistant to penicillin, oxacillin, ampicillin and vancomycin were identified. Class A pse1 β-lactamase, class 1 integron and the blaTEM gene were detected in 20.8%, 20.8% and 8.3% of the identified isolates, respectively.
31	Igbinosa EO et al., 2011 [ 65 ]	Sewage	Final effluents WWTP	Vibrio spp. strains (including V. parahaemolyticus, V. fluvialis and V. vulnificus) resistant to erythromycin, chloramphenicol, nitrofurantoin, cefuroxime and cephalothin were detected. SXT antibiotic resistance gene cluster (floR, strB, sul2, dfrA18 and dfrA1) were also identified in % of these strains.
32	Johnning A, et. Al 2015 [ 66 ]	Sewage and environmental water	Up and downstream WWTP and from industrially polluted sites and sediment samples from a pristine lake	Mutations in chromosomal genes gyrA and parC, associated with resistance to fluoroquinolone, were detected in E. coli communities. High abundance of mutations was correlated with the concentration of fluoroquinolones in investigated samples (i.e., samples polluted with high concentrations of fluoroquinolone).
33	Sahlström L et al., 2009 [ 67 ]	Sewage and clinical samples	WWTP and isolates from humans and chickens	Vancomycin-resistant isolates of Enterococcus spp., including E. faecium, E. hirae and E. durans, were detected.
34	Araújo C et al., 2010 [ 68 ]	Sewage	Sludge and sewage of urban and poultry slaughter house WWTP	Vancomycin-resistant isolates of Enterococcus spp., including E. faecium, E. gallinarum and E. casseliflavus, which were also resistant to varied groups of antimicrobial drugs (kanamycin, tetracycline, erythromycin, ciprofloxacin, ampicillin, streptomycin and gentamicin), were detected.
35	Soge O et al., 2009 [ 69 ]	Sewage and environmental water	Water, soil and sewage	The majority of Clostridium perfringens strains recovered from water samples were found to carry more than one ARG encoding resistance to tetracycline and erythromycin.
36	Zhang X et al., 2009 [ 70 ]	Sewage	WWTP	Enterobacteriaceae strains carrying class 1 integrons and ARGs associated with resistance to trimethoprim (dfr17) and streptomycin (aadA5) were detected.
37	Odjadjare EO et al., 2010 [ 71 ]	Sewage	WWTP final effluent, discharge point and upstream and downstream of the discharge point	Most of the Listeria spp. isolates recovered from final effluents were MDR strains.
38	Okoh AI et al., 2010 [ 72 ]	Sewage	WWTP final effluents	MDR Vibrio spp. strains that showed resistance to varied antimicrobial drugs (including sulfamethoxazole, trimethoprim, cotrimoxazole, chloramphenicol, streptomycin, ampicillin, tetracycline, nalidixic acid and gentamicin) were detected.
39	Yang H et al., 2010 [ 73 ]	Sewage and environmental waters	Soil, water and faecal samples	Higher copies of tetracycline ARGs and higher abundance of tetracycline-resistant bacteria were identified in farm (cattle), compared to nonfarm, wastewater samples.
40	Garcia-Armisen T et al., 2011 [ 74 ]	Environmental water	Sewage-contaminated rivers	Most of the ARB detected in the Zenne river, downstream of Brussels, were MDR strains. The abundance of AMR communities (heterotrophic and faecal bacteria) was not correlated with the level of contamination of river water with sewage.
41	Colomer-Lluch M et al., 2011 [ 75 ]	Sewage and environmental water	Urban sewage and river water	β-lactamase genes (blaTEM and blaCTX-M9) and one encoding penicillin-binding protein (mecA) were detected in the DNA phages recovered from all the samples.
42	Fuentefria DB et al., 2011 [ 76 ]	Sewage and environmental water	Hospital wastewater and superficial water	Genetically distinct populations of AMR Pseudomonas aeruginosa were detected in these different environments (hospital wastewater and superficial water that received this wastewater discharge).
43	Gaze WH et al., 2011 [ 77 ]	Sewage	Industrial waste, sewage sludge and pig slurry	Higher prevalence of class 1 integrons was detected in bacteria recovered from sewage sludge and pig slurry (exposed to antibiotic residues and detergents) compared to agricultural soils to which these waste products are amended. It has been estimated that ~1019 bacteria carrying class 1 integrons enter the United Kingdom environment by disposal of sewage sludge each year.
44	Ma L et al., 2011 [ 78 ]	Sewage	WWTP	The abundance of bacteria (E. coli, Klebsiella spp. and Aeromonas veronii) carrying class I integronase gene intI1 were higher in effluent compared to influent wastewater. intI1 was detected in 20.4%, 30.9% and 38.9% of bacteria recovered from influent, activated sludge and effluent wastewater, respectively. This study suggested a role of activated sludge (characterized by high biomass and biodiversity) in developing AMR through the dissemination of integrons.
45	Mokracka J et al., 2011 [ 79 ]	Sewage	WWTP	Quinolone- and fluoroquinolone-resistant strains constituted 56% and 50.4% of recovered integron-bearing E. coli strains (including diarrheagenic and extraintestinal strains carrying virulence traits), respectively. Virulent extraintestinal strains constituted ~50% of all isolates and were detected in samples recovered from all wastewater treatment stages, including final effluent.
46	Amaya E et al., 2012 [ 80 ]	Sewage and environmental waste water	Hospital wastewater and well waters	High levels of MDR E. coli isolates were recovered from samples collected from both hospital wastewaters and environmental well water. E. coli strains harbouring blaCTX-M1 and blaCTX-M9 were predominated in samples collected from wells and hospital wastewater, respectively.
47	Mokracka J et al., 2012 [ 81 ]	Sewage	Municipal WWTP	MDR Enterobacteriaceae strains carrying class 1 and class 2 integrons (12.1%; 221 out of 1832) were identified in different stages of a municipal wastewater treatment plant (61.5%, 12.7% and 25.8% of ARB were originated from raw sewage, aeration tank and final effluent, respectively). The abundance of ARGs and MDR bacteria, particularly the level of ARG diversity and B-lactamase-producers, were higher in final effluent samples.
48	Splindler A et al., 2012 [ 82 ]	Sewage	Untreated hospital effluents	Half of Pseudomonas spp. isolates recovered from untreated hospital effluent wastewater were MDR strains, while 41.9% (52 out of 124) of the isolates were found to carry intlI.
49	Gundogdu, A. et al., 2012 [ 83 ]	Sewage	Untreated hospital wastewaters and WWTP	High level of ESBL-producing E. coli isolates were detected in untreated hospital wastewaters (blaSHV), with distinct genotypes (blaCTX-M) associated with the samples recovered from WWTP.
50	Zarfel, G et al., 2013 [ 84 ]	Sewage and clinical samples	Sewage and human urinary tract infection samples	ESBL-producing bacteria carrying blaCTX-M were predominated in both sewage sludge (blaCTX-M-15) and UTI (blaCTX-M-1) samples. The study suggested the occurrence of a genetic exchange between the ESBL-resistant E. coli populations from human infections and those present in sewage sludge.
51	Colomer-Lluch M et al., 2013 [ 85 ]	Sewage and environmental water	Sewage and river water samples	Quinolone-resistant E. coli strains of clinically relevant ST69 and ST131 (carrying virulence traits) predominated in samples recovered from urban wastewater and both river and wastewaters, respectively. Similar virulence and macro-restriction profiles were identified in environmental and human isolates of ST131.
52	Sadowy E et al., 2014 [ 86 ]	Sewage and environmental water	Wastewater, riverine estuary and anthropogenically impacted marine catchment basin	AMR isolates of Enterococcus spp., especially fluoroquinolone- and aminoglycoside-resistant E. faecium that shared virulence determinants and ST similar to nosocomial high-risk enterococcal clonal complexes (HiRECC), were detected.
53	Gao P et al., 2015 [ 87 ]	Sewage	WWTP	Positive correlations were observed between the occurrence of heavy metals (e.g., zinc and lead and ereB, mefA&E and ermB) and antibacterial residues (e.g., triclosan with ereA, ereB, mefA&E and ermB) in urban wastewaters and the abundance of erythromycin-resistant genes.
54	Nishiyama M et al., 2015 [ 88 ]	Sewage and environmental water	Sewage and urban river water samples	vanC-type vancomycin-resistant E. faecium and E. faecalis, which are the major types of enterococci in humans, were detected in both sewage and urban river water samples.
55	Zhang S et al., 2015 [ 89 ]	Sewage	WWTP	Gram-negative and -positive isolates dominated WWTP influent and effluent samples, respectively. The frequency of detection of tetracycline-, sulphonamide-, streptomycin- and β-lactam-resistance genes (except sulA and blaCTX-M) were higher in ARB from influent compared to effluent samples. The abundances of ARGs in activated sludge were higher in aerobic compartments than in anoxic ones.
56	Simo Tchuinte PL et al., [ 90 ]	Sewage	Hospital effluent and sludge	Novel class 3 integrons with oxacillinase gene cassette, including aminoglycoside and β-lactam-resistant genes (blaOXA-10, blaOXA-368 or blaOXA-2), were identified in Acinetobacter johnsonii, Aeromonas allosaccharophila and Citrobacter freundii, which were recovered from hospital effluent samples.
57	Young S et al., 2016 [ 91 ]	Sewage and environment water	Water and sediment samples from sewage spill site	Nosocomial pathogen; vancomycin-resistant E. faecium (harbouring vanA associated with a high resistance level) were isolated from water and sediment for up to 3 days after a sewage spill. vanA gene were found to persist for an additional week within these environments. Culturable levels of enterococci in water exceeded recreational water guidelines for 2 weeks following the spill, declining about five orders of magnitude in sediments and two orders of magnitude in the water column over 6 weeks.
58	Lee J et al., 2017 [ 92 ]	Sewage	Food waste-recycling wastewater (FRW), manure and sewage sludge	The abundance of ARGs was greatest in manure, followed by sewage sludge and FRW. However, different patterns in the diversity and mechanisms of ARGs were identified. ARG associated with β-lactam resistance were higher in the FRW, and sulfonamides-resistant genes are higher in sludge. Total ARGs is associated with class 1 integron only in manure and sludge.
59	An XL et al., 2018 [ 93 ]	Sewage	Influent, activated sludge and effluents of urban WWTP	High concentration of class 1 integron gene cassette (including trimethoprim, aminoglycoside and beta-lactam resistance genes) were identified in activated sludge.
60	Haller L et al., 2018 [ 94 ]	Sewage	Hospital effluents	MDR bacteria belonging to Enterobacteriaceae and other species, including ESBL- and carbapenemase-producers, were identified.
61	Galler H et al.,2018 [ 95 ]	Sewage	Activated sludge	Clinically relevant ARBs, including ESBL-Enterobacteriaceae, MRSA and vancomycin-resistant Enterococcus spp., were detected. ARG associated with resistance to β-lactam, vancomycin (vanA) and methicilin (mecA) were identified.
62	Quach-Cu J et al., 2018 [ 96 ]	Sewage	Raw wastewater, activated sludge and secondary and tertiary WWTP effluent	The abundance of blaSHV, blaTEM and sul1 were higher in raw wastewater than other samples.
63	Yousfi K et al., 2019 [ 97 ]	Sewage	Hospital effluents	Enterobacteriaceae isolates (including E. coli and K. pneumoniae) and non-Enterobacteriaceae Gram-negative bacterial isolates (including A. baumannii and A. hydrophila) showed high levels of resistance to β-lactam and non-β-lactam-antibiotics, and most of them are multidrug-resistant. This study is the first study that found genes encoding carbapenemases, including blaOXA-23 and blaOXA-48, like in A. baumannii, K. oxytoca and S. xiamenensis in Algerian hospital effluents.