Clean, fresh water is one of the most important natural resources of the world. Yet large amounts of chemicals, including antibiotics, are released into the environment through wastewater.
For example, researchers that looked into the release of wastewater from Indian pharmaceutical production facilities estimated that processed water from one plant contained 45 kg of ciprofloxacin per day (in comparison, the total daily consumption in Sweden is 9 kg). Downstream from that plant the sediments contained high amounts of antibiotics and, as a natural consequence, antibiotic resistant bacteria.
The most common treatment technique is activated sludge, a cheap and efficient method to remove organic material. It relies on a complex microbial community in the treatment process, which is recycled within the plant. If high levels of antibiotics are deposited to the plant, this ecosystem may be disturbed, resulting in lowered efficacy of the treatment process. Importantly however, this treatment technique is not capable of clearing chemicals such as antibiotics.
Selection of antibiotic resistance by wastewater
Wastewater with high antibiotic content is problematic for at least two reasons: resistance selection including dispersal, and proper function of waste processing.
This was demonstrated in a study where researchers collected samples from a sewage treatment plant receiving wastewater from a pharmaceutical factory. Samples were taken from different stages of the treatment process, and viable bacteria were cultured. 93 strains of bacteria were isolated and investigated further. The strains were identified and their susceptibility to 39 antibiotics from 12 classes was determined with disc diffusion methodology. The presence of integrons, mobile elements capable of transferring resistance between bacteria, was also determined.
The study found that a high degree of antibiotic resistance was found in the isolated strains, including:
- All strains were resistant to at least 5 antibiotics,
- 86% were resistant to 20 or more antibiotics and
- 53% of the strains were resistant to 29 or more antibiotics.
- The most common type of resistance was to two β-lactam antibiotics, ampicillin and mecillinam, both occurring in 98% of the strains, respectively.
- 62% of the strains were resistant to ciprofloxacin.
- A mobile element was found in 95% of the isolates.
A prior study had revealed alarmingly high rates of antibiotic resistance in river sediments downstream of the plant, and therefore indicated that the presence of the highly resistant bacteria was not confined within the treatment plant.
Waste water plants failing?
Building on the experiences above, a more recent study published in November 2016 looked into the bacterial diversity in the water treatment plant. Researchers visited the same wastewater treatment plant, again sampling all steps in the process. This time, the samples were studied with DNA sequencing to study the total composition of the microbial community in the samples.
More than one million sequences were analysed and grouped according to similarity. The diversity of bacteria was lowest in the beginning of the treatment process and increased toward the secondary sludge. Compared with similar data from sewage treatment plants in China with no pharmaceutical industry waste, the diversity was significantly lower. This suggests that lack of microbial diversity affects the efficiency of the treatment process, resulting in release of polluted water.
Need for action
Wastewater containing high levels of antibiotics is a serious environmental problem. Techniques which effectively remove antibiotics and other chemicals need to be deployed before release to wastewater treatment plants, and measure to better control dispersal of antibiotic resistance through processed water or remaining sludge urgently need to be required and put in place.
A promising step forward in this regard is the draft of the Indian National Action Plan on Antimicrobial Resistance where the government within three years intends to introduce limits to the emission of antibiotics and a framework for monitoring antibiotic residues in wastewater.
Such timebound targets and measures should serve as inspiration to other countries with pharmaceutical production capacity to drastically improve the monitoring and restriction of antibiotic release into the environment.
Larsson DG, de Pedro C, Paxeus N. Effluent from drug manufactures contains extremely high levels of pharmaceuticals. J Hazard Mater. 2007 Sep 30;148(3):751-5. http://dx.doi.org/10.1016/j.jhazmat.2007.07.008
Marathe NP, Regina VR, Walujkar SA, Charan SS, Moore ERB, Larsson DGJ, Shouche YS. A Treatment Plant Receiving Waste Water from Multiple Bulk Drug Manufacturers Is a Reservoir for Highly Multi-Drug Resistant Integron-Bearing Bacteria. PLOS One, October 29, 2013. http://dx.doi.org/10.1371/journal.pone.0077310
Marathe NP, Shetty SA, Shouche YS, Larsson DGJ. Limited Bacterial Diversity within a Treatment Plant Receiving Antibiotic-Containing Waste from Bulk Drug Production PLOS One, November 3, 2016. http://dx.doi.org/10.1371/journal.pone.0165914