FATE AND TRANSPORT OF FLUOROQUINOLONE AND ITS RESISTANT BACTERIA IN RIVERINE ENVIRONMENT

Gothwal, R and T, Shashidhar (2017) FATE AND TRANSPORT OF FLUOROQUINOLONE AND ITS RESISTANT BACTERIA IN RIVERINE ENVIRONMENT. PhD thesis, Indian institute of technology Hyderabad.

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Abstract

Antibiotics are the products of rapid innovations in the health sector, and their usage has changed the pattern of the modern way of living. Ever since it has been recognized that they can be used as a medicine to treat and prevent infectious diseases, their market has been expanding out of bounds. The manufacturing plants were established majorly in developing countries to match the increasing demands. The main pathway for antibiotics to enter into aquatic environment is considered from hospitals and domestic sewage in developed countries. Whereas, improper disposal of effluents of bulk drug manufacturing units is the major pathway for antibiotics to enter into aquatic environment in developing countries. There are several bulk drug manufacturing industries in and around Hyderabad (India), and common effluent treatment plants to treat their effluents. The treated effluent is mixed with the domestic sewage at Amberpet wastewater treatment plant (WWTP) and then drained into the Musi River. This study was about the occurrence and distribution of Fluoroquinolone antibiotic, and to understand the prevalence its resistant bacteria contamination in Musi river. The improper disposal of bulk drug manufacturing units can cause high levels of antibiotic contamination in the river, which in return might result in becoming an active site for the spread of drug resistance. Seven fluoroquinolones (ciprofloxacin, lomefloxacin, ofloxacin, norfloxacin, enrofloxacin, pefloxacin and difloxacin) were selected as target antibiotics due to the presence of their production facilities in the area, and their presence was also confirmed by a preliminary analysis for fluoroquinolones in the sludge of domestic wastewater treatment plant (WWTP). In addition to antibiotics, heavy metals also act as selective agents and promoting the antibiotic resistance. Hence nine heavy metals (Cr, Mn, Fe, Co, Ni, Cu, Zn, Mo, and Pb) and other pollution parameters were quantified as well as correlated. Multiple regression analyses were also performed to find out the functional relationship between pollution parameters (antibiotic, heavy metal, total organic carbon, susceptible bacteria, resistant bacteria), which might affect the resistant culture directly and indirectly. The results of the study provided information that concentration of fluoroquinolones was found to be a thousand-fold higher than the usual concentrations found in rivers of developed countries. The research findings also indicated that anthropogenic impacts could promote the spread of resistant bacteria, as positive correlation was observed with the presence of fluoroquinolone and heavy metals. For a better understanding of the relationship between fluoroquinolones and resistant bacteria, a mathematical model was developed for temporal and spatial transport of the fluoroquinolones antibiotics and resistance gene carrying bacteria in the aquatic environment of the river. It included state variables for organic matter, heavy metals, fluoroquinolones, susceptible and resistant bacteria in the water column and sediment bed. This model included plasmid dynamics, as mobile resistance genes are majorly being carried on plasmids and these plasmid-mediated resistance genes are transferable between different bacterial species by conjugation (horizontal resistance transfer). The processes in the model comprised of advection, dispersion, adsorption, diffusion, degradation, settling, re-suspension, microbial growth rate, segregation and transfer of resistance genes. The equations with appropriate boundary conditions were solved using implicit-explicit scheme. A sequential iterative technique was used to solve the non-linear partial differential equations. In this approach, the advection part was discretized based on the Monotone Upwind Scheme for Conservation Laws (MUSCL) which is globally second-order accurate and non-oscillatory. The diffusive part was approximated by a second-order central difference. Finite difference approximations of transport equations were written, with reference to the finite difference grid method. The developed model was applied to Musi River, was calibrated and validated with observed field data. The model was able to reproduce similar spatial pattern to observed data. Sensitivity analysis and uncertainty analysis was performed to understand the effect of stochasticity in model parameters on unpredictability in the end results. The sources of uncertainty were grouped into environmental, demographic and anthropogenic stochasticity, and Poisson distribution was employed for diffusion approximation of model parameters and variables. With this exercise, we were able to identify that, variation in the population of resistant bacteria in sediments were insignificant due to stochastic nature of model parameters and variables. Hypothetical management scenarios were simulated with the model to predict the concentration of antibiotic resistant bacteria. Results from the simulation of different hypothetical cases suggested that concentration of antibiotic, organic matter, segregation and horizontal transfer rate of resistance gene majorly dictates the population of antibiotic resistant bacteria. As it is costly to remove antibiotics from effluents of bulk drug manufacturing industries, emphasis can be given to reducing organic matter which can limit the growth rate of bacteria and can reduce total bacterial population in the river. Reduction in antibiotic concentration can reduce the selection pressure and can minimize the river segment with resistant bacteria, but complete removal of antibiotics may not result in complete elimination of antibiotic resistant bacteria.

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