The data on persistence, bioaccumulation and toxicity for trimethoprim are from fass.se. The information on risk comes from the reports by Goodpoint. Trimethoprim is monitored within the framework of EU water legislation.
Persistence. Trimethoprim is potentially persistent.
Bioaccumulation. Trimethoprim has low potential for bioaccumulation.
Toxicity. Trimethoprim has moderate chronic toxicity.
Risk. See the reports from Goodpoint.
Fass environmental information
Fass environmental information for trimethoprim, Bactrim (sulfamethoxazole, trimethoprim) from Roche (downloaded 2020-11-16).
- 0% after 28 days of incubation BOD/ThOD (OECD 301 F)
- 4% after 28 days of incubation BOD/ThOD (OECD 301 D)
- 27% after 28 days of incubation BOD/ThOD (OECD 301 D with co-metabolism)."
There are data from more tests, see Fass environmental information."Trimethoprim is neither readily, nor inherently biodegradable. This justifies the phrase 'Trimethoprim is potentially persistent.'"
Bioaccumulation: Log Kow = 0.64 experimental, method unknown.
Acute toxicity: There are data for 3 trophic levels, lowest for cyanobacteria (Anabaena flos-aquae) NOEC 72 h (yield) = 1.0 mg/L (OECD 201).
PEC/PNEC is based on sales data in Sweden in year 2017. PEC/PNEC = 0.008 which gives the risk insignificant, i.e. consideration has not been given to measured levels in the environment.
Report Goodpoint 2016
Concentrations of trimethoprim in Swedish wastewater treatment plants is likely to select for bacterial resistance.
Trimethoprim is included in Region Stockholm's table of pharmaceuticals with risk for negative environmental impact according to the environmental program, 2017–2021. Trimethoprim has been detected in treated wastewater, surface water and fish i Region Stockholm.
Report Goodpoint 2018
Comparative assessment of environmental risk and risk of resistance selection in the environment using trimethoprim and pivmecillinam in Sweden.
From a resistance-selection-risk perspective in wastewater treatment plants, pivmecillinam appears to be a slightly better alternative than trimethoprim. [...] Nitrofurantoin is therefore preferable to quinolones (e.g., ciprofloxacin), trimethoprim and pivmecillinam from an environmental point of view (selection risk) when appropriate from a clinical perspective.
EU water legislation
Trimethoprim is monitored within the framework of EU water legislation. "Substances for which doubt exists about their toxicity, or for which the sensitivity, reliability or comparability of the available monitoring methods are not adequate, should not be included in the watch list. The sulfonamide antibiotic sulfamethoxazole and the diaminopyrimidine antibiotic trimethoprim, the antidepressant venlafaxine and its metabolite O-desmethylvenlafaxine, a group of three azole pharmaceuticals (clotrimazole, fluconazole and miconazole) ... The inclusion of the various pharmaceuticals is consistent with the EU Strategic Approach to Pharmaceuticals in the Environment, and the inclusion of the two antibiotics is also consistent with the European One Health Action Plan against Antimicrobial Resistance (AMR), which supports the use of the watch list to ‘improve knowledge of the occurrence and spread of antimicrobials in the environment’."
Low concentrations of antibiotics
Studies have shown that even low concentrations of antibiotics in the environment may trigger antibiotic resistance and therefore measures should be taken to ensure that as little as possible ends up in our environment.
The Wise list
Trimethoprim is recommended in the Wise list. The Wise list is the drug formulary of essential medicines for common diseases in Region Stockholm from the Drug and Therapeutics Committee. Environmental classification of pharmaceuticals is taken into consideration, sometimes with other environmental aspects, when selecting pharmaceuticals for the Wise list. When comparable pharmaceuticals are equivalent to medical effects, safety and pharmaceutical efficacy, environmental impact and price are considered.
Suggestions on how to reduce emissions of trimethoprim
Concrete proposals on how to work to reduce emissions of environmentally harmful pharmaceuticals on the list have been developed in close cooperation with Region Stockholm Drug and Therapeutics Committee's expert groups. The action proposals were developed from an environmental perspective. The patient's best always goes first and several pharmaceuticals on the list are also included in the Wise list. However, for such pharmaceuticals, there may be measures that could reduce the environmental impact.
Concrete proposal for trimethoprim
- Trimethoprim is recommended in Wise list after urinary cultivation if the bacterium is sensitive.
- In the empirical treatment of lower urinary tract infection without fever, the Wise list recommendation is nitrofurantoin, which is better than trimethoprim or pivmecillinam from an environmental point of view. Antibiotic rotation at the individual level is recommended to reduce the risk of resistance development.
- For antibiotics, the general rule is as restrictive use as possible without risking the patient's health. Relevant cultivations are important in order to choose antibiotics that have a good effect with as narrow spectrum as possible.
- Fass.se för vårdpersonal
- Goodpoint. Prioritering av läkemedel med miljörisk inom SLL. Stockholm: Goodpoint; 2016. Rapport LS 2016–0634.
- Binelli A, Parolini M, Cogni D, Pedriali A, Provini A. A multi-biomarker assessment of the impact of the antibacterial trimethoprim on the non-target organism Zebra mussel (Dreissena polymorpha). Comp Biochem Physiol C Toxicol Pharmacol. 2009;150:329-36.
- IVL Swedish Environmental Research Institute Ltd. Fick J, Lindberg RH, Kaj L, Brorström-Lundén E. Results from the Swedish National Screening Programme 2010. Subreport 3. Pharmaceuticals.
- IVL Swedish Environmental Research Institute Ltd Fick J, Lindberg RH, Fång J, Magnér J, Kaj L, Brorström-Lundén E. Screening 2014. Analysis of pharmaceuticals and hormones in samples from WWTPs and receiving waters. Rapport C 135.
- Bengtsson-Palme J, Larsson DG. Concentrations of antibiotics predicted to select for resistant bacteria: Proposed limits for environmental regulation. Environ Int. 2016;86:140-9.
- Provtagningar av läkemedelsrester i vatten, sediment och fisk för Region Stockholm.
- Region Stockholm. Förteckning över miljöbelastande läkemedel med åtgärdsförslag framtagen inom ramen för Region Stockholms miljöprogram 2017–2021.
- Goodpoint. Jämförande bedömning av miljörisk och risk för resistensselektion i miljön vid användning av trimetoprim och pivmecillinam. Stockholm: Goodpoint; 2018.
- Official Journal of the European Union. Commission implementing decision (EU) 2020/1161 of 4 August 2020.
- Official Journal of the European Union. Commission implementing decision (EU) 2022/1307 of 22 July 2022.
- Gullberg E, Cao S, Berg OG, Ilbäck C, Sandegren L, Hughes D et al. Selection of resistant bacteria at very low antibiotic concentrations. PLoS Pathog. 2011;7:e1002158.
- Region Stockholms läkemedelskommitté. Kloka listan (the Wise list).
- Region Stockholm's Drug and Therapeutics Committee. The Wise list 2015.
Author: Health and Medical Care Administration, Region Stockholm