, Volume 45, Issue 4, pp 479–491 | Cite as

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

  • Christoph LübbertEmail author
  • Christian Baars
  • Anil Dayakar
  • Norman Lippmann
  • Arne C. Rodloff
  • Martina Kinzig
  • Fritz Sörgel
Original Paper



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.


Antibiotics Antifungal agents Antimicrobial resistance Multidrug-resistant (MDR) pathogens Carbapenemase-producing Enterobacteriaceae (CPE) Non-fermenters Colonization Infection Selection pressure 


Author contributions

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.

Supplementary material

15010_2017_1007_MOESM1_ESM.pdf (1.4 mb)
Supplementary material 1 (PDF 1437 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Christoph Lübbert
    • 1
    • 2
    Email author
  • Christian Baars
    • 3
  • Anil Dayakar
    • 4
  • Norman Lippmann
    • 2
    • 5
  • Arne C. Rodloff
    • 2
    • 5
  • Martina Kinzig
    • 6
  • Fritz Sörgel
    • 6
    • 7
  1. 1.Division of Infectious Diseases and Tropical Medicine, Department of Gastroenterology and RheumatologyLeipzig University HospitalLeipzigGermany
  2. 2.Interdisciplinary Center for Infectious DiseasesLeipzig University HospitalLeipzigGermany
  3. 3.Ressort InvestigationNorth German Broadcasting Corporation (NDR)HamburgGermany
  4. 4.NGO GamanaMadhapurIndia
  5. 5.Institute for Medical Microbiology and Epidemiology of Infectious DiseasesLeipzig University HospitalLeipzigGermany
  6. 6.IBMP-Institute for Biomedical and Pharmaceutical ResearchNürnberg-HeroldsbergGermany
  7. 7.Institute of PharmacologyUniversity of Duisburg-EssenEssenGermany

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