1 Persistence of Antibiotics in the Natural Environment: Scoping Review Protocol
2 Irene Bueno1*, Huan He2, André J. Nault3, Sarah Ziemann4, Lauren Degn4, William A. Arnold2a,
3 Kristine H. Wammer4a
4
5 1. Department of Veterinary and Biomedical Sciences, University of Minnesota. 1971
6 Commonwealth Ave. Saint Paul, MN 55108. United States.
7 2. Department of Civil, Environmental, and Geo- Engineering, University of Minnesota. 500
8 Pillsbury Drive S.E. Minneapolis, MN 55455-0116. United States.
9 3. Health Sciences Libraries, University of Minnesota. 1988 Fitch Avenue. Saint Paul, MN
10 55108. United States.
11 4. Department of Chemistry, College of Arts & Sciences, University of St. Thomas. 2115
12 Summit Ave. Saint Paul, MN 55105. United States.
13
14 a: Co-senior authors
15 *Corresponding author: Irene Bueno ([email protected])
16
17 Abstract
18 Background: Antibiotics and their metabolites released into aquatic and soil environments have
19 the potential to affect their microbial communities and can be a selection pressure to drive
20 antimicrobial resistance emergence and spread. However, data about the persistence of
21 antibiotics and metabolites into the natural environment are still lacking.
22 Objectives: The goal of this manuscript is to describe the protocol that will be used to conduct a
23 formal scoping review of the current literature to address the following question: “What is known
1
24 from the existing literature about degradation of a selected group of antibiotic compounds in
25 water, sediment, and soil?”.
26 Eligibility criteria: Eligible studies will be primary research, in English, from any geographic
27 location, published between 2000-2020, include water, sediment, and/or soil samples, were
28 conducted in natural systems and/or laboratory studies with relevant data applied to natural
29 systems, include data related to transformation by sunlight, biodegradation, and/or sorption
30 processes, and include data for any of the following compounds: i) sulfonamides:
31 sulfachlorpyridazine, sulfadiazine, sulfadimethoxine, sulfamethazine, sulfamethoxazole,
32 sulfapyridine; ii) macrolides: erythromycin, roxithromycin, tylosin, azithromycin; iii)
33 tetracyclines: chlortetracycline, doxycycline, oxytetracycline, tetracycline; iv) fluoroquinlones:
34 ciprofloxacin, enrofloxacin, norfloxacin, ofloxacin; v) beta-lactams: penicillins; vi) others:
35 carbadox, trimethoprim, lincomycin.
36 Sources of evidence: The following databases will be searched: Pubmed/MEDLINE, CAB
37 Abstracts, Web of Science, and Scopus from 2000-2020.
38 Charting methods: We will extract data on general and specific study characteristics, study
39 systems, and transformation processes/antibiotic compounds combinations.
40
41
42
43
44
45
46
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47 Introduction
48 Rationale
49 Antimicrobial resistance (AMR) is a well-recognized global public health threat (WHO, 2020).
50 According to the Centers for Disease Control and Prevention (CDC), close to three million
51 people in the U.S. develop antibiotic-resistant infections each year, and this leads to more than
52 35,000 deaths (CDC, 2019). As AMR increases, attention is being directed towards the role of
53 the natural environment. Watersheds, in particular, are recipients of antibiotic residues,
54 antimicrobial resistant bacteria (ARB), and antimicrobial resistance genes (ARG) released from
55 effluents of anthropogenic sources (Bueno et al., 2017; Bueno et al., 2018; Huijbers et al., 2015).
56 These sources include but are not limited to wastewater treatment plants, animal agriculture and
57 aquaculture, ethanol plants, crop production, and pharmaceutical manufacturing plants.
58 Antibiotics and their metabolites released from these sources might pose an indirect risk to
59 human, animal, and ecosystem health by driving the emergence of antimicrobial resistance in
60 environmental bacteria (Rahube et al., 2016).
61
62 Studying the fate of antibiotics and their metabolites in the natural environment through field
63 work is challenging and limited by resources. To overcome this restraint, mathematical and
64 geospatial modeling play an important role in predicting the fate of these compounds within the
65 complexity and uncertainties of natural systems (Singer, et al., 2006; Spicknall, et al., 2013). To
66 fully understand the persistence of antibiotics in the natural environment and fully parameterize
67 mathematical and geospatial models, information on degradation rates for different compounds is
68 needed. Relevant removal processes include transformation by sunlight, degradation by
69 microorganisms, and sorption to settling particles (Kümmerer, 2009). For targeted antibiotic
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70 compounds, a scoping review will be conducted to compile relevant biodegradation, sorption,
71 and direct and indirect photolysis rate constants of the target antibiotics to assess which gaps are
72 most critical to fill to inform future transformation studies. In addition, data from the scoping
73 review will be used to parameterize antibiotic dissemination models in the natural environment.
74 Objectives
75 The objective of this protocol is to describe the methods that will be used to address the
76 following review question: What is known from the existing literature about degradation for a
77 selected group of antibiotic compounds in water, sediment, and soil? In particular, what is
78 known about:
79 • transformation by sunlight (direct and indirect photolysis rate constants)?
80 • degradation by microorganisms (biodegradation rate constants)?
81 • sorption to settling particles (partition coefficients as a function of particle organic
82 carbon content, mineral composition, and pH)?
83 Methods
84 Protocol and registration
85 This protocol was prepared using the Preferred Reporting Items for Systematic Reviews and
86 Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) (Tricco et al., 2018) and it will
87 be published in the University of Minnesota Libraries Digital Conservancy
88 (https://conservancy.umn.edu/).
89 Eligibility criteria
90 Studies are eligible for this review if they meet the following criteria:
91 a) Primary research.
92 b) Published in English.
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93 c) Published between 2000-2020. The year 2000 was chosen because it was when analytical
94 methods became sensitive enough to quantify antibiotic’s environmentally-relevant
95 concentrations.
96 d) Conducted in natural systems and/or in laboratory settings that provide relevant data to the
97 natural systems.
98 e) Investigate any of the following transformation studies: sorption, biodegradation, and/or
99 photolysis.
100 f) Investigate any of the following compounds: i) sulfonamides: sulfachlorpyridazine,
101 sulfadiazine, sulfadimethoxine, sulfamethazine, sulfamethoxazole, sulfapyridine; ii) macrolides:
102 erythromycin, roxithromycin, tylosin, azithromycin; iii) tetracyclines: chlortetracycline,
103 doxycycline, oxytetracycline, tetracycline; iv) fluoroquinlones: ciprofloxacin, enrofloxacin,
104 norfloxacin, ofloxacin; v) beta-lactams: penicillins (broadly); vi) others: carbadox, trimethoprim,
105 and/or lincomycin.
106 Information sources
107 The following databases will be searched for relevant studies: Pubmed/MEDLINE, CAB
108 Abstracts, Web of Science, and Scopus, with a publication limit of 2000-2020. All citations will
109 be exported to EndNote® X9 Desktop and de-duplicated. The final set of articles resulting from
110 the de-duplication will be uploaded to the Rayaan webtool as a .bib file for the first phase of the
111 screening process (Ouzzani et al., 2016).
112 Search
113 The search strings for each one of the search databases and for each one of the transformation
114 processes were drafted by an experienced librarian (André J. Nault) with input from experts in
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115 the field (Drs. Kristine H. Wammer, Huan He, and William A. Arnold). The search strings can
116 be found at the end of this protocol.
117 Selection of sources of evidence
118 The selection of relevant studies will be done with the Rayaan webtool (Ouzzani et al., 2016) by
119 a team of four reviewers. Each article will be assessed by two independent reviewers. Reviewers
120 will resolve any conflicts about the selection of articles into the study during weekly meetings,
121 and with the help of a third reviewer if needed. The first screening phase will consist of only
122 reviewing the title and abstract of each article, and the second screening phase will consist of
123 reviewing the full text of those articles that are retained after the first screening phase. Prior to
124 screening articles, the screening process will be pre-tested by all four reviewers with a random
125 set of articles, and the process will be improved based on feedback from this pre-testing phase.
126 First screening phase (title/abstract)
127 1) Is the title/abstract available? If not, the record will be excluded.
128 2) Is the title/abstract in English? If not, the record will be excluded.
129 3) Does the title/abstract refer to primary research? If not, the record will be excluded. We will
130 exclude reviews and conference proceedings.
131 4) Does the title/abstract include a natural system (river, lake, stream, creek, estuary, marine,
132 soil, other), a laboratory experiment, or a modeling study with relevant data to the natural
133 system of interest? If not, the record will be excluded. Engineered systems such as
134 wastewater treatment plants will be excluded.
135 5) Does the title/abstract refer to marine sediments or marine biodegradation (i.e.,
136 biodegradation in marine environment)? If so, does it also refer to photolysis-
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137 photodegradation? If the study solely reports on marine sediments and/or marine
138 biodegradation without involving photodegradation, the study will be excluded.
139 6) Does the title/abstract include water, sediment, or soil samples? If not, the record will be
140 excluded unless it is a relevant laboratory and/or modeling study.
141 7) Does the title/abstract evaluate any of the following processes: photolysis (UV-A/B radiation
142 with a wavelength between 290-400 nm, sunlight, simulated sunlight, indirect photolysis
143 induced by hydroxyl radical, carbonate radical, singlet oxygen, triplet excited organic
144 matter), biodegradation (all systems except marine), or sorption (all systems except marine),
145 and/or persistence? If not, the record will be excluded.
146 8) Does the title/abstract include any of the following target compounds: i) sulfonamides:
147 sulfachlorpyridazine, sulfadiazine, sulfadimethoxine, sulfamethazine, sulfamethoxazole,
148 sulfapyridine; ii) macrolides: erythromycin, roxithromycin, tylosin, azithromycin; iii)
149 tetracyclines: chlortetracycline, doxycycline, oxytetracycline, tetracycline; iv)
150 fluoroquinlones: ciprofloxacin, enrofloxacin, norfloxacin, ofloxacin; v) beta-lactams:
151 penicillins (broadly); vi) others: carbadox, trimethoprim, and/or lincomycin? If not, the
152 record will be excluded.
153 If the answer to any of the above questions is ‘No’, the record will be excluded (in the Rayyan
154 webtool they will be labeled as ‘Exclude’). If the answer to all the above questions is ‘Yes’ or
155 ‘Maybe’ (or a combination of both), records will move to the 2nd screening phase where the full
156 text will be reviewed (in the Rayyan webtool they will be labeled as ‘Include’ or ‘Maybe’). The
157 full text for included studies will be retrieved through the University of Minnesota Libraries and
158 imported into Mendeley 1.19.8.
159 Second screening phase (Full text)
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160 The same questions that were used during the first screening phase will be applied here. In
161 addition, the following questions will be assessed:
162 1) Is the full text available? If not, the record will be excluded.
163 2) Does the full text include information about both a parent antibiotic compound and its
164 product/transformation processes? If the study describes the parent compound without data for
165 the transformation processes or products, it will be excluded.
166 If the answer to any of the above questions is ‘No’, the study will be excluded. If the answer to
167 all the above questions is ‘Yes’ or ‘Maybe’, the study will be included.
168 Data charting process
169 Data charting will be conducted in the REDCap web application (Harris et al., 2009)
170 independently by two reviewers. The reviewers will resolve any conflicts during weekly
171 meetings and/or with the help of a third reviewer. The data charting tool will be pre-tested using
172 a random sample of studies, and the tool will be improved based on the reviewer’s feedback.
173 Data items
174 The data that will be extracted from each study will include the following:
175 1) General information: author(s), journal, publication year, aim of the study, geographic region.
176 2) Study characteristics: study design, system/setting used (e.g. river), sample type(s),
177 transformation processes, time period when the study took place, specific antibiotics evaluated.
178 3) Outcome data: data for each transformation process/antibiotic combination will be extracted.
179 Critical appraisal of individual sources of evidence
180 A critical appraisal of individual sources of evidence will not be conducted as this is a scoping
181 review of the literature and not a systematic review (Sargeant & O'Connor, 2020).
182
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183 Synthesis of results
184 Studies will be grouped according to the transformation processes reported, and within those, by
185 antibiotic compounds. Descriptive statistics will be conducted for the outcome data for each one
186 of the transformation process/antibiotic combinations within the different study systems/settings
187 and sample types. A narrative summary will also be conducted that will include general
188 information and specific studies characteristics. A meta-analysis will be conducted if there are
189 enough data for each transformation process/antibiotic compound combination. In addition, any
190 data gaps will be identified.
191 Funding
192 This work was funded by the Minnesota Environmental and Natural Resources Trust Fund (M.L.
193 2018, Chp. 214, Art. 4, Sec. 02, Subd. 04h.) as recommended by the Legislative and Citizen
194 Commission on Minnesota Resources.
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196
197
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198 References
199 Bueno, I., Williams-Nguyen, J., Hwang, H., Sargeant, J. M., Nault, A. J., & Singer, R. S. (2017). 200 Impact of point sources on antibiotic resistance genes in the natural environment: a 201 systematic review of the evidence. Animal Health Research Reviews, 18(2), 112-127. 202 https://doi.org/10.1017/S146625231700007X. 203 Bueno, I., Williams‐Nguyen, J., Hwang, H., Sargeant, J., Nault, A. J., & Singer, R. (2018). 204 Systematic review: impact of point sources on antibiotic‐resistant bacteria in the natural 205 environment. Zoonoses and Public Health, 65(1), e162-e184. 206 https://doi.org/10.1111/zph.12426. 207 CDC. (2019). Antibiotic resistance threats in the United States. Retrieved from 208 https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-threats-report-508.pdf. 209 Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009). Research 210 electronic data capture (REDCap)—a metadata-driven methodology and workflow 211 process for providing translational research informatics support. Journal of Biomedical 212 Informatics, 42(2), 377-381. https://doi.org/10.1016/j.jbi.2008.08.010. 213 Huijbers, P. M., Blaak, H., de Jong, M. C., Graat, E. A., Vandenbroucke-Grauls, C. M., & de 214 Roda Husman, A. M. (2015). Role of the environment in the transmission of 215 antimicrobial resistance to humans: a review. Environmental Science & Technology, 216 49(20), 11993-12004. https://doi.org/10.1021/acs.est.5b02566. 217 Kümmerer, K. (2009). Antibiotics in the aquatic environment–a review–part I. Chemosphere, 218 75(4), 417-434. https://doi.org/10.1016/j.chemosphere.2008.11.086. 219 Ouzzani, M., Hammady, H., Fedorowicz, Z., & Elmagarmid, A. (2016). Rayyan-a web and 220 mobile app for systematic reviews. Systematic Reviews, 5, 210. In. 221 https://doi.org/10.1186/s13643-016-0384-4. 222 Rahube, T. O., Marti, R., Scott, A., Tien, Y.-C., Murray, R., Sabourin, L., . . . Topp, E. (2016). 223 Persistence of antibiotic resistance and plasmid-associated genes in soil following 224 application of sewage sludge and abundance on vegetables at harvest. Canadian journal 225 of Microbiology, 62(7), 600-607. https://doi.org/10.1139/cjm-2016-0034. 226 Sargeant, J. M., & O'Connor, A. M. (2020). Scoping reviews, systematic reviews, and meta- 227 analysis: Applications in veterinary medicine. Frontiers in Veterinary Science, 7, 11. 228 https://doi.org/10.3389/fvets.2020.00011. 229 Singer, R. S., Ward, M. P., & Maldonado, G. (2006). Can landscape ecology untangle the 230 complexity of antibiotic resistance? Nature Reviews Microbiology, 4(12), 943-952. 231 doi:10.1038/nrmicro1553. 232 Spicknall, I. H., Foxman, B., Marrs, C. F., & Eisenberg, J. N. (2013). A modeling framework for 233 the evolution and spread of antibiotic resistance: literature review and model 234 categorization. American Journal of Epidemiology, 178(4), 508-520. 235 https://doi.org/10.1093/aje/kwt017. 236 Tricco, A. C., Lillie, E., Zarin, W., O'Brien, K. K., Colquhoun, H., Levac, D., . . . Weeks, L. 237 (2018). PRISMA extension for scoping reviews (PRISMA-ScR): checklist and 238 explanation. Annals of Internal Medicine, 169(7), 467-473. https://doi.org/10.7326/M18- 239 0850. 240 World Health Organization (WHO). (2020). Antimicrobial resistance. Retrieved from 241 https://www.who.int/health-topics/antimicrobial-resistance. 242
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243 Search strings
244 Scopus
245 TITLE-ABS-KEY ( sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR
246 sulfamethazine OR sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR
247 tylosin OR chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR
248 ciprofloxacin OR enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR
249 lincomycin OR sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR beta-
250 lactam) AND TITLE-ABS-KEY ( lake OR river OR stream OR aquatic) AND TITLE-ABS-
251 KEY ( sediment ) AND TITLE-ABS-KEY (adsorption OR sorption OR persistence) AND (
252 PUBYEAR AFT 1999 AND PUBYEAR BEF 2022 ) AND ( LIMIT-TO (
253 LANGUAGE,"English" ) ) AND NOT TITLE-ABS-KEY (photocatalysis OR catalysis OR
254 catalyst OR photocatalyst OR photocatalytic OR catalytic OR Tio2 OR “titanium dioxide” OR
255 charcoal OR bioremediation OR bioreactor OR synthesis OR “activated sludge” OR biochar)
256
257 TITLE-ABS-KEY ( sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR
258 sulfamethazine OR sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR
259 tylosin OR chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR
260 ciprofloxacin OR enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR
261 lincomycin OR sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR beta-
262 lactam) AND TITLE-ABS-KEY ( lake OR river OR stream OR aquatic OR sediment) AND
263 TITLE-ABS-KEY (biodegradation OR biotransformation OR co-metabolism) AND (
264 PUBYEAR AFT 1999 AND PUBYEAR BEF 2022 ) AND ( LIMIT-TO (
265 LANGUAGE,"English" ) ) AND NOT TITLE-ABS-KEY (photocatalysis OR catalysis OR
1
266 catalyst OR photocatalyst OR photocatalytic OR catalytic OR Tio2 OR “titanium dioxide” OR
267 charcoal OR bioremediation OR bioreactor OR synthesis OR “activated sludge” OR biochar)
268
269 TITLE-ABS-KEY ( sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR
270 sulfamethazine OR sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR
271 tylosin OR chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR
272 ciprofloxacin OR enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR
273 lincomycin OR sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR beta-
274 lactam) AND TITLE-ABS-KEY ( lake OR river OR stream OR aquatic OR sediment) AND
275 TITLE-ABS-KEY (photodegradation OR phototransformation OR photolysis OR "indirect
276 photolysis" OR "hydroxyl radical" OR "singlet oxygen") AND ( PUBYEAR AFT 1999 AND
277 PUBYEAR BEF 2022 ) AND ( LIMIT-TO ( LANGUAGE,"English" ) ) AND NOT TITLE-
278 ABS-KEY (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic OR
279 catalytic OR Tio2 OR “titanium dioxide” OR charcoal OR bioremediation OR bioreactor OR
280 synthesis OR “activated sludge” OR biochar)
281 CAB Abstracts
282 [mp=abstract, title, original title, broad terms, heading words, identifiers, cabicodes]
283 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
284 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
285 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
286 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
287 sulfonamide OR sulfa drug OR macrolide OR fluoroquinolone OR beta-lactam).mp. AND (lake
288 OR river OR stream OR aquatic).mp. AND (sediment).mp. AND (adsorption OR sorption OR
2
289 persistence).mp. NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR
290 photocatalytic OR catalytic OR Tio2 OR titanium dioxide OR charcoal OR bioremediation OR
291 bioreactor OR synthesis OR activated sludge OR biochar).mp.
292
293 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
294 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
295 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
296 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
297 sulfonamide OR sulfa drug OR macrolide OR fluoroquinolone OR beta-lactam).mp. AND (lake
298 OR river OR stream OR aquatic OR sediment).mp. AND (biodegradation OR biotransformation
299 OR co-metabolism).mp. NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR
300 photocatalytic OR catalytic OR Tio2 OR titanium dioxide OR charcoal OR bioremediation OR
301 bioreactor OR synthesis OR activated sludge OR biochar).mp.
302 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
303 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
304 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
305 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
306 sulfonamide OR sulfa drug OR macrolide OR fluoroquinolone OR beta-lactam).mp. AND (lake
307 OR river OR stream OR aquatic OR sediment).mp. AND (photodegradation OR
308 phototransformation OR photolysis OR indirect photolysis OR hydroxyl radical OR singlet
309 oxygen).mp. NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic
310 OR catalytic OR Tio2 OR titanium dioxide OR charcoal OR bioremediation OR bioreactor OR
311 synthesis OR activated sludge OR biochar).mp.
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312 Web of Science
313 (ALL=((sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
314 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
315 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
316 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
317 sulfonamide OR "sulfa drug" OR macrolide OR fluoroquinolone OR "beta lactam") AND (lake
318 OR river OR stream OR aquatic) AND (sediment) AND (adsorption OR sorption OR
319 persistence) NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic
320 OR catalytic OR Tio2 OR "titanium dioxide" OR charcoal OR bioremediation OR bioreactor OR
321 synthesis OR "activated sludge" OR biochar) )) AND LANGUAGE: (English)
322 Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI,
323 CCR-EXPANDED, IC Timespan=2000-2021
324 (ALL=((sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
325 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
326 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
327 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
328 sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR “beta lactam”) AND (lake
329 OR river OR stream OR aquatic OR sediment) AND (biodegradation OR biotransformation OR
330 “co-metabolism”) NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR
331 photocatalytic OR catalytic OR Tio2 OR “titanium dioxide” OR charcoal OR bioremediation OR
332 bioreactor OR synthesis OR “activated sludge” OR biochar) )) AND LANGUAGE: (English)
333 Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI,
334 CCR-EXPANDED, IC Timespan=2000-2021
4
335 (ALL=((sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
336 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
337 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
338 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
339 sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR “beta lactam”) AND (lake
340 OR river OR stream OR aquatic OR sediment) AND (photodegradation OR phototransformation
341 OR photolysis OR “indirect photolysis” OR “hydroxyl radical” OR “singlet oxygen”) NOT
342 (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic OR catalytic OR
343 Tio2 OR “titanium dioxide” OR charcoal OR bioremediation OR bioreactor OR synthesis OR
344 “activated sludge” OR biochar) )) AND LANGUAGE: (English)
345 Indexes=SCI-EXPANDED, SSCI, A&HCI, CPCI-S, CPCI-SSH, BKCI-S, BKCI-SSH, ESCI,
346 CCR-EXPANDED, IC Timespan=2000-2021
347
348 Pubmed
349 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
350 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
351 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
352 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
353 sulfonamide OR "sulfa drug" OR macrolide OR fluoroquinolone OR "beta lactam") AND (lake
354 OR river OR stream OR aquatic) AND (sediment) AND (adsorption OR sorption OR
355 persistence) NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic
356 OR catalytic OR Tio2 OR "titanium dioxide" OR charcoal OR bioremediation OR bioreactor OR
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357 synthesis OR "activated sludge" OR biochar) AND 2000/01/01:2021/03/23[dp] AND
358 (english[Language])
359
360 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
361 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
362 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
363 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
364 sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR “beta lactam”) AND (lake
365 OR river OR stream OR aquatic OR sediment) AND (biodegradation OR biotransformation OR
366 “co-metabolism”) NOT (photocatalysis OR catalysis OR catalyst OR photocatalyst OR
367 photocatalytic OR catalytic OR Tio2 OR “titanium dioxide” OR charcoal OR bioremediation OR
368 bioreactor OR synthesis OR “activated sludge” OR biochar) AND 2000/01/01:2021/03/23[dp]
369 AND (english[Language])
370
371 (sulfachlorpyridazine OR sulfadiazine OR sulfadimethoxine OR sulfamethazine OR
372 sulfamethoxazole OR sulfapyridine OR erythromycin OR roxithromycin OR tylosin OR
373 chlortetracycline OR doxycycline OR oxytetracycline OR tetracycline OR ciprofloxacin OR
374 enrofloxacin OR norfloxacin OR ofloxacin OR carbadox OR trimethoprim OR lincomycin OR
375 sulfonamide OR “sulfa drug” OR macrolide OR fluoroquinolone OR “beta lactam”) AND (lake
376 OR river OR stream OR aquatic OR sediment) AND (photodegradation OR phototransformation
377 OR photolysis OR “indirect photolysis” OR “hydroxyl radical” OR “singlet oxygen”) NOT
378 (photocatalysis OR catalysis OR catalyst OR photocatalyst OR photocatalytic OR catalytic OR
6
379 Tio2 OR “titanium dioxide” OR charcoal OR bioremediation OR bioreactor OR synthesis OR
380 “activated sludge” OR biochar) AND 2000/01/01:2021/03/23[dp] AND (english[Language])
381 Total from Pubmed after de-duplication was 367.
382
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