Insight into the fluoroquinolone resistance, sources, ecotoxicity, and degradation with special emphasis on ciprofloxacin

https://doi.org/10.1016/j.jwpe.2021.102218Get rights and content

Highlights

  • Ciprofloxacin is a second-generation fluoroquinolone.

  • It is used to treat wide range of bacterial infections.

  • Fluoroquinolones exerts its ecotoxicity on living beings.

  • Fluoroquinolones induced resistance in bacteria is studied.

  • Recent remediation strategies have been discussed for ciprofloxacin removal.

Abstract

The presence of antibiotics in wastewater, domestic water, and sewage has been found to produce ecotoxicological effects on living beings. Fluoroquinolones (FQs) are recognized as critically important and highly prioritized antimicrobial and are frequently used in veterinary and human medicine. The recalcitrance of these antibiotics along with their poor metabolism has led to their detection in manures and wastewater. Ciprofloxacin (CIP) is a synthetic and commonly prescribed FQ and the metabolite of enrofloxacin, the veterinary drug. CIP has negative effects on the flora and fauna. Due to the emergence of bacterial resistance against FQs, special attention is given to the environmental degradation of these antibiotics by microorganisms. Physicochemical processes and bioremediation are employed for the removal of CIP, but the lipophilic and hydrophobic nature of the antibiotics acts as a hindrance to their complete removal from the environment. The present review gives an insight into the sources of FQs in the environment, their detection, and their impact on living beings. CIP removal is being paid special attention and recent trends in its removal are discussed.

Introduction

Antibiotics are one of the greatest advancements in the field of medicine, and they have been employed for the treatment of a wide range of illnesses and for promoting animal growth. The antibiotics are partially absorbed by the system, and a considerable fraction is excreted either in its original form or metabolized form. Therefore, the use of animal excreta in agriculture can act as one of the major routes of the entry of antibiotics into the environmental matrices [1]. The entry of antibiotics into the aquatic environment at lower concentrations poses a long-term risk to aquatic organisms [2]. Excessive usage of antibiotics has resulted in antibiotic pollution in the environment, and these polluted sites act as hotspots for the spread of antibiotic resistance in environmental bacteria. The subinhibitory concentration of the antibiotics exerts selective pressure on microbes, driving the evolution of antibiotic-resistant bacteria [3].

Among the antibiotics, FQs are of interest since they have been increasingly used in households, hospitals, and veterinary applications [4]. In biological treatment plants, more than 70% of CIP and norfloxacin (NOR) gets adsorbed on the sludge surface as sludge is an accumulator of the antibiotics. The contaminated sludge is used as biosolids in agricultural fields owing to the multitude of hazards [5]. FQs are used worldwide in veterinary and human medicine. They are the third-largest class of antibiotics. Up to 70% of the FQs are excreted in an unmetabolized form, which promotes resistance in microbial populations. FQs are recalcitrant to degradation and have high adsorption affinities which result in their persistent nature and have a reported half-life up to 580 days in soil and 10.6 days in surface water [6]. Over the last few years, the FQs are detected frequently in wastewater. But, there were no reports which showed their degradation in the conventional WWTPs. The quinolone emergence was accidental as a by-product of an antimalarial agent, chloroquine. Nalidixic acid is the first quinolone to be discovered and showed antibacterial activity against Enterobacteria [7]. Nalidixic acid is used in the treatment of simple urinary tract infections only. Later, other quinolones were synthesized which broaden the antibacterial spectrum of these drugs. Different functional groups are introduced into the structure of quinolone which gives new compounds with better pharmacokinetics, a wide spectrum of action, high stability, and less toxicity [8]. Table 1 shows the development of quinolone antibiotic generations. FQs are eliminated via renal excretion and hepatic metabolism. FQs get only partially metabolized in the liver and excreted via urine and bile. CIP is excreted in urine (65%) and feces (25%) [23].

Quinolones are used in the treatment of both Gram-positive and Gram-negative bacterium. The latest generation is active against anaerobic bacteria and bacteria which are resistant to sulfonamides and Beta-lactams. NOR and ofloxacin are used as both human and veterinary medicine, whereas danofloxacin, marbofloxacin, enrofloxacin, and sarafloxacin are used are veterinary medicine, and CIP is used as a human medicine only [24].

CIP is a second-generation FQ that is frequently detected in the effluents of wastewater treatment plants (WWTPs), soils, surface water, and groundwater [25]. CIP is active against a wide range of bacteria and is used in the treatment of bacterial infections. Table 2 shows the CIP detection using various analytical techniques. It acts by inhibiting the bacterial deoxyribonucleic acid (DNA) replication while interacting with the topoisomerase II DNA gyrase and topoisomerase IV in bacteria [30]. Mainly the broad-spectrum activity of the FQs is due to the binding of the topoisomerase on the ketone and carboxyl group. The high antibacterial activity of the FQs is due to the presence of fluorine at the 6th position. Substitutions at ethyl, cyclopropyl, and fluorophenyl position and piperazine ring can have an impact on the biological activity [31]. CIP is one of the most widely used FQs in human medicines [32]. It is one of the main metabolites of enrofloxacin (ENR). ENR is N-deethylated in animals which results in active CIP showing enhanced antimicrobial activity [33]. CIP presence has been detected in environmental matrices such as soil [34], sediment [35], surface water, wastewater [36], and manure [37]. According to the reports of Gonzales-Martinez [38], CIP has an impact on the community structure of the microbes, and their catabolic diversity.

Section snippets

Sources of FQs in the environment

Animal manure, WWTP effluent, biosolids contaminated with FQs are potential reservoirs of the antibiotics. The mobility of the FQs in the water depends on the solubility, the solubility of 1 g/L is said to be hydrophilic and resistant to hydrolysis [39]. The water solubility of the CIP is 30 g/L and ENR is 130 g/L [40]. FQs enter the environment via both veterinary and human waste. Waste streams that originate from the hospitals, animal farms, and residential areas contain the FQs antibiotic.

Ecotoxicity of FQs and its impact on living organisms

Ecotoxicological data are available for less than 1% of the drugs. Antibiotics are designed to act on specific tissues or organs or target a specific molecular or metabolic pathway, but it affects non-target organisms also. FQs and their metabolites are highly toxic to algae, plants, bacteria, crustaceans, and fishes [56]. The FQs compounds exert ecological effects on the soil microbial communities [57]. The negative impacts of FQs include the ecotoxicological effects, decrease in the microbial

WWTPs in the spread of FQs resistance

WWTPs are designed to minimize the concentration of pathogens and antibiotics [71]. These WWTPs receive hospital, industrial, and domestic waste and become a hotspot for the promotion of multi-drug resistance in bacteria [72]. The antibiotic-resistant genes (ARGs) are present in sediments, groundwater, wetlands, and surface water [73]. The antibiotics employed in livestock treatment and animal feed may also play a role in the development of resistance in bacteria. The WWTPs discharges into

Antibiotic removal in the WWTPs

The removal efficiency of antibiotics was also studied by Wang et al. [75], the quinolones along with beta-lactams and lincomycin was removed up to 77% followed by tetracyclines, whereas the sulfonamides, macrolides, and trimethoprim are recalcitrant to degradation so exhibit the lowest removal in WWTPs. The beta-lactams get rapidly hydrolyzed via enzymatic and chemical hydrolysis. Quinolones get absorbed into the sewage sludge and have high sorption constant, which can explain their highest

FQs induced resistance in bacteria

Extensive use of FQs has led to the increased resistance to antimicrobials. Bacterial resistance has emerged rapidly. Escherichia coli, Salmonella spp., Mycobacterium tuberculosis, Clostridium spp., Klebsiella pneumoniae, Staphylococcus aureus, Neisseria gonorrhea, Pseudomonas aeruginosa, Proteus mirabilis are reported to be resistant to FQs. Table 4 shows the Quinolone resistance mechanism in bacteria. Initially, the resistance was related to chromosomal mechanisms, and mainly due to the

Degradation of FQs

Antibiotics are non-biodegradable and highly persistent in the environment. CIP degrades very slowly and is persistent in soil for up to 4 months, thus creating a micro-environment for the antibiotic-resistant bacterial strains in the soil matrix [111]. CIP is a second-generation FQ and is detected at high concentrations in wastewaters. The unrestricted use of the CIP has aggravated the increase of CIP-resistant bacteria. The physical and chemical methods of degradation are expensive and

Degradation of FQs using fungi and bacteria

Fungi and bacteria are used for the removal of antibiotics via biotransformation, mineralization, and biodegradation. Agrocybe praecox, Dichomitus squalens, Gloeophyllum striatum, Gloeophyllum trabeum, Irpex lacteus, Pleurotus ostreatus, Bjerkandera adusta, Clitocybe odora, Clitocybula dusenii are the fungal species that are involved in the degradation of CIP. Bacteria and fungi are reported to transform CIP with fungi offering certain advantages over bacteria in FQs degradation. In the case of

Plants in the removal of CIP

The sewage sludge that contains antibiotics is used as a fertilizer in fields [129]. Antibiotics reach the soil matrices, get accumulated in plants, and affect the microorganisms. Growth promoters used in animal husbandry reach the manure in the original form or as metabolites, and ultimately to fields. High antibiotics concentration gets accumulated in the soil, and strongly influences the plants and microorganisms. Antibiotics and metabolites reach the soil and get mineralized by soil

Phytoremediation of CIP

Vetiver grass is used in the phytoremediation of antibiotics. Vetiver grass can tolerate inorganic and organic pollutants. A study by Panja et al. [131], showed the ability of Vetiver grass in the removal of CIP from aquatic media with a major aim for the development of the plant-based method for the treatment of wastewater [131]. The transformation and elimination of CIP were evaluated in the study. In 30 days, 80% of CIP was removed and transformation products of CIP in the tissues of Vetiver

CIP removal using modified advanced oxidation processes (AOPs)

AOPs include technologies such as hydrogen peroxide (H202), Fenton (Fe(II)/H2O2), ultraviolet radiation (UV), and ozone (O3) [133]. The ozonation of FQs was performed by Liu et al. [134]. 2 mg/L of O3 led to 100% removal efficiency. Ozonation is effective in the decontamination of the contaminants from the effluents of wastewater but can lead to sore throat, headaches, and nose and eye irritation [134]. Water containing bromite can react with residual ozone to form carcinogenic bromate [135].

Conclusions

The antibiotics and the resistant genes are released into the ecosystem which has led to antibiotic pollution in the environment. The antibiotics have a dreadful impact on the non-target bacteria and disrupt their ecological functions. They can either cause inhibition or disappearance of bacterial groups i.e.; they can either have a bactericidal or bacteriostatic effect or can confer resistance in the bacteria by generating phenotypic and genetic variability. Both physicochemical and biological

Funding

This study was supported by the funding agency, National Agricultural Science Fund, Indian Council of Agricultural Research, Delhi, India.

Research involving human participants and/or animals

The study do not related to animals or humans.

Informed consent

N/A.

Declaration of competing interest

No conflicts of interest.

Acknowledgment

Financial assistance provided by NASF research grant (project entitled “Bioremediation of chemical contaminants and their complexes present in drainage water with high dynamic flux used for irrigation in urban and peri-urban agriculture”), sanction no. NASF/CA-6030/2017-18 is highly acknowledged. The author Kushneet Kaur Sodhi highly acknowledges the University Grant Commission (UGC), Government of India for providing the stipend.

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