Environmental pollution with antimicrobial agents from bulk drug manufacturing industries in Hyderabad, South India, is associated with dissemination of extended-spectrum beta-lactamase and carbapenemase-producing pathogens
- 8.9k Downloads
High antibiotic and antifungal concentrations in wastewater from anti-infective drug production may exert selection pressure for multidrug-resistant (MDR) pathogens. We investigated the environmental presence of active pharmaceutical ingredients and their association with MDR Gram-negative bacteria in Hyderabad, South India, a major production area for the global bulk drug market.
From Nov 19 to 28, 2016, water samples were collected from the direct environment of bulk drug manufacturing facilities, the vicinity of two sewage treatment plants, the Musi River, and habitats in Hyderabad and nearby villages. Samples were analyzed for 25 anti-infective pharmaceuticals with liquid chromatography–tandem mass spectrometry and for MDR Gram-negative bacteria using chromogenic culture media. In addition, specimens were screened with PCR for bla VIM, bla KPC, bla NDM, bla IMP-1, and bla OXA-48 resistance genes.
All environmental specimens from 28 different sampling sites were contaminated with antimicrobials. High concentrations of moxifloxacin, voriconazole, and fluconazole (up to 694.1, 2500, and 236,950 µg/L, respectively) as well as increased concentrations of eight other antibiotics were found in sewers in the Patancheru–Bollaram industrial area. Corresponding microbiological analyses revealed an extensive presence of extended-spectrum beta-lactamase and carbapenemase-producing Enterobacteriaceae and non-fermenters (carrying mainly bla OXA-48, bla NDM, and bla KPC) in more than 95% of the samples.
Insufficient wastewater management by bulk drug manufacturing facilities leads to unprecedented contamination of water resources with antimicrobial pharmaceuticals, which seems to be associated with the selection and dissemination of carbapenemase-producing pathogens. The development and global spread of antimicrobial resistance present a major challenge for pharmaceutical producers and regulatory agencies.
KeywordsAntibiotics Antifungal agents Antimicrobial resistance Multidrug-resistant (MDR) pathogens Carbapenemase-producing Enterobacteriaceae (CPE) Non-fermenters Colonization Infection Selection pressure
Study conception and design: CL, CB, ACR, and FS. Identification of sampling sites and acquisition of data: CL, CB, and AD. Provision of documentary images: CL and CB. Performance of the laboratory experiments: NL and MK. Data analysis and interpretation of the results: CL, CB, NL, TE, ACR, MK, and FS. Drafting of the manuscript: CL. Critical revision of the manuscript: CL, CB, AD, TE, NL, ACR, MK, and FS.
Compliance with ethical standards
Conflict of interest
All authors deny any potential conflicts of interest.
The authors did not receive any external funding.
- 1.World Health Organization. Antimicrobial resistance 2014: global report on surveillance. Geneva: World Health Organization; 2014.Google Scholar
- 2.O’Neill J. The review on antimicrobial resistance 2014. Tackling drug-resistant infections globally: final report and recommendations. http://www.amr-review.org. Accessed 20 Jan 2017.
- 15.Ashbolt NJ, Amézquita A, Backhaus T, et al. Human health risk assessment (HHRA) for environmental development and transfer of antibiotic resistance. Environ Health Persp. 2013;121:993–1001.Google Scholar
- 23.Changing Markets. Superbugs in the Supply Chain, 2016: how pollution from antibiotics factories in India and China is fuelling the global rise of drug-resistant infections. http://www.mightyearth.org/wp-content/uploads/2016/10/changing-market-superbugs-in-the-supply-chain-guard-font-fin-print.pdf. Accessed 20 Jan 2017.
- 25.India online pages. Population of Hyderabad 2016. http://www.indiaonlinepages.com/population/hyderabad-population.html. Accessed 20 Jan 2017.
- 26.Central Pollution Control Board of India (CPCB). Final action plan for improvement of environmental parameters in critically polluted areas of Patancheru–Bollaram cluster, Andhra Pradesh, 2010. http://cpcb.nic.in/divisionsofheadoffice/ess/Patancheru-Bollaram.pdf. Accessed 20 Jan 2017.
- 27.Central Pollution Control Board of India (CPCB). Note on the implementation of the action plan and its compliance for the critically polluted area of Patancheru–Bollaram in Telangana, 2016. http://cpcb.nic.in/zonaloffice/banglore/CEPI_Bollaram.pdf. Accessed 20 Jan 2017.
- 28.The Hans India. Pharma still pollutes Patancheru, 2015. http://www.thehansindia.com/posts/index/Telangana/2015-11-28/Pharma-still-pollutes-Patancheru/189407. Accessed 20 Jan 2017.
- 34.The Indian Express. India has 60.4 per cent people without access to toilet: study 2015. http://indianexpress.com/article/india/india-news-india/india-has-60-4-per-cent-people-without-access-to-toilet-study/. Accessed 20 January 2017.