Treatment of Antibiotics in Wastewater Using Advanced Oxidation Processes (AOPs)

Antibiotics are nonbiodegradable, can survive at aquatic environments for long periods and they have a big potential bio-accumulation in the environment. They are extensively metabolized by humans, animals and plants. After metabolization, antibiotics or their metabolites are excreted into the aquatic environment. Removal of these compounds from the aquatic environment is feasible by different processes. But antibiotics are not treated in conventional wastewater treatment plants efficiently. During the last years studies with advanced oxidation processes (AOPs) for removal of these pharmaceuticals from waters has shown that they can be useful for removing them fully. Advanced oxidation processes (AOPs) can work as alternatives or complementary method in traditional wastewater treatment, and highly reactive free radicals, especially hydroxyl radicals (OH) generated via chemical (O3/H2O2, O3/OH ), photochemical (UV/O3, O3/H2O2) reactions, serve as the main oxidant. This study presents an overview of the literature on antibiotics and their removal from water by advanced oxidation processes. It includes almost all types of antibiotics which are consumed by human and veterinary processes. It was found that most of the investigated advanced oxidation treatment processes for the oxidation of antibiotics in water are direct and indirect photolysis with the combinations of H2O2, TiO2, ozone and Fenton’s reagent.


Introduction
The "antibiotic" term qua generic is used to specify any class of organic molecule that blocks or ravage microbes by specific interactions with bacterial marks, without considering any compound or class [1]. Antibiotics are designed to act very effectively even at low doses and, in case of intracorporal administration, to be completely excreted from the body after a short time of residence [2]. They are nonbiodegradable and can survive in aquatic environments for long periods [3]. The entrance of these compounds into the environment owing to anthropogenic sources can result in a potential risk for organisms. Although antibiotics exist at residual levels, they can cause resistance in bacterial populations, making them inactive in the treatment of several diseases in the near future [4,5]. And they cause endocrine-disrupting effects when they are consumed by living organisms. They interfere with the synthesis, secretion, transport, binding, action, and elimination of hormones in the human body [6].
The annual usages of antibiotics are determined between 100,000 and 200,000 t globally [7]. Traditionally, these compounds were not accepted as environmental contaminants, but their existence in the aquatic ecosystems has become an apprehension as biological impacts and potential threat to the environment [8][9][10]. Furthermore, it has been shown up that residual antibiotics are able to support the election of genetic variants of microorganisms concluding in the existence of antibiotic-resistant pathogens [11,12].
Removal of these compounds from the aquatic environment is feasible by different processes. This can be carried out using biotic (biodegradation) or nonbiotic (chemical oxidation and advanced oxidation) ways. But antibiotics are not treated in conventional wastewater treatment plants efficiently. During the last years, studies with advanced oxidation processes (AOPs) for removal of these pharmaceuticals from waters have shown that they can be useful for removing them completely. In this chapter, we aim to introduce a review of literature on antibiotics and their removal from water by advanced oxidation processes. An effort to include as many studies as possible was made in order to highlight important findings and present the knowledge currently available on the removal efficiency of antibiotics from wastewater.

General description of antibiotics
Antibiotic as a word is reproduced from the Greek anti (¼against) and biotikos (¼living).
Most of the living organisms are able to compose matters that can influence other organisms' capacity for growth, endurance, and reproduction. Microorganisms have a versatile ability to inhibit the growth and purpose of other microorganisms and produce and release biologically effective substances at the appropriate moment. We denominate substances of this kind as antibiotics [13].
In addition, organisms' ability to compose antibiotics has been of great importance for the development of different life forms and their capability to accommodate to new circumambient. Nowadays, antibiotics are important components for the functions of various biological systems.
antibiotics have toxic effects on humans, animals, and also microorganisms even at low concentrations. At the same time, they are nonbiodegradable and can survive in the environment even in the conventional wastewater treatments. So they cause bio-accumulation [3]. Therefore, the presence of antibiotics in the environment can cause the occurrence of antibiotic-resistant bacteria [17]. They are not treated in the conventional wastewater treatment plants completely. According to the recent studies, advanced oxidation processes (AOPs) are useful to remove these toxic compounds completely from waters.

Sources of antibiotics in the environment
In these last years, the use of antibiotics in veterinary and human medicine has been widespread, and consequently, the possibility of water contamination with such compounds has been increased [19]. These pollutants are continually discharged into the natural environment as parent compounds, metabolites/degradation products, or both forms by a diversity of input sources as shown in Figure 1 [5].
Fertilizers present in the fields can contaminate soil and consequently surface and groundwater through runoff or filtration [20]. Likewise, human antibiotics which are present into the environment through discharge, entering in the sewage and reaching the Waste-water treatment plants (WWTP). Despite most of WWTPs are not projected to remove highly polar micropollutants [19], they can be transferred to surface waters and reach groundwater after leaching.
The sludge produced in WWTPs is utilized as soil manure and can cause problems when used as a fertilizer. Some other significant pollution source is the direct delivery of veterinary antibiotics through the implementation in aquaculture. Inappropriate elimination of unused/expired Figure 1. Pathways of antibiotics in the environment [5,16]. drugs can also be considered as significant points of contamination. These are derived directly from sewage discharge or landfills deposition, waste effluents from manufacture, or accidental spills during manufacturing or distribution [5].
At optimum operation conditions, for instance sufficient contact time, it is possible to mineralize the target contaminant to CO 2 and H 2 O, the most stable end products of chemical oxidation. For this reason, the extraordinary definition of AOPs on chemical processes is that they are completely described as "environmentally friendly" [42].
The basic treatment of AOPs can be explained in two steps: one is the generation of hydroxyl radicals and the other is the oxidative reaction of these radicals with molecules [43]. The dissolved organic pollutants can be converted into CO 2  Ground water*/bank filtrate (ng L À1 )

Ozonation
Ozone is a powerful oxidizer and has been increasingly used for the treatment of wastewater [46]. High pH values (>11.0) causes high efficiency and ozone behaves randomly with all organic and inorganic compositions present in the reacting medium [45]. Ozone reacts with substances in two different ways: indirect and direct. These two reaction pathways are managed by different type of kinetics and lead to different oxidation products [47].
Simplified reaction mechanism of ozone at high pH is given in below:

Ozone/hydrogen peroxide (peroxone) process (O 3 /H 2 O 2 )
The principle of peroxonation is based on the coupling between ozone (O 3 ) and H 2 O 2 , resulting in the generation of oxidizing radicals. As pointed out by Zaviska et al. [47], the peroxonation mechanism could be more productive than ozonation alone, and H 2 O 2 impacts on increasing the decomposition percentage of O 3 in water, which generates a larger number of very reactive •OH radicals [49]. Because of the high cost of ozone generation, this combination makes the process economically feasible [50]. Several factors limit the usefulness of the peroxonation process such as important energetic consumption, low water solubility of ozone, and its sensitivity to several factors [51]. A general mechanism of peroxon process is given below: Solution pH is critical as well for the process output like other AOPs. Higher production rates of hydroxyl radicals will be obtained by the addition of hydrogen peroxide to the aqueous O 3 solution at high pH conditions. Independence of peroxone process from any light source or UV delivers a certain benefits to this operation [44].
•OH radical is generated through the agency of reaction between H 2 O 2 and Fe þ2 salts as described below.
Thus, composed hydroxyl radical can react with Fe(II) to develop ferric ion (Fe(III)) (Eq. (16)) As an alternative, hydroxyl radicals are able to react with organic pollutants and start oxidation in a waste stream, Reactions can result into the degradation of Fe þ3 to Fe þ2 at a value of pH between 2.7 and 2.8.
In these circumstances, iron can be considered as a true catalyst [156].
Process efficiency is closely related to the solution pH whose optimal values are between 2 and 4 as well as the COD:H 2 O 2 :catalyst ratio in the feed [52].
Basically, the Fenton process possesses several important advantages for water/wastewater treatment [48,53]: • A plain and adaptable operation permitting easy execution in existing plants • Easy-to-use and relatively cheap chemicals The vacuum ultraviolet (UV) is absorbed by all the materials from water to air, therefore can only be transferred in a vacuum. The absorption of a VUV photon causes breaking of one or more bond. As an example, water is decomposed by VUV photolysis has a high feasibility for the oxidative degradation of organic pollutants in water. In spectral domain (approx. 140-200 nm), it produces hydrogen atoms and hydroxyl radicals. Due to the high absorption cross-section of water and quantum yields of water homolysis of 0.45-0.3 at stimulation wavelengths (between 140 and 185 nm) provide productive local concentrations of hydroxyl and hydrogen radicals. VUV photolysis is a new technique for water treatment and suggests the benefit to generate unusually high local concentrations of oxidative reactive intermediates without the addition of supplementary oxidant [44,54].

Hydrogen peroxide/UV (H 2 O 2 /UV) process
Hydrogen peroxide can be photolyzed by UV radiations by producing the homolytic scission of the O-O bond of the H 2 O 2 and resulting the formation of •OH radicals which can also be supplied to the decomposition of H 2 O 2 by secondary reactions [48]. The main reaction is given below: UV/H 2 O 2 process is effective in mineralizing organic pollutants. As an disadvantage the process cannot use solar light as the source of UV light owing to the fact that the required UV energy is not available in the solar spectrum [55]. Over and above, H 2 O 2 has poor UV absorption characteristics. At last, special reactors designed for UV illumination are required [56].
The major factors influencing the process are the amount of H 2 O 2 used, presence of bicarbonate, wastewater pH, the initial concentration of the object compound, and reaction time [57].

Ozone/UV (O 3 /UV) process
The advanced oxidation process with ozone and UV radiation is initiated by the photolysis of ozone. Hydroxyl radicals can be composed by those in hydrogen peroxide under UV and/or ozone. The equations are given below: All kinds of UV light origins can be utilized for this process, especially low-pressure mercury vapor lamps. The O 3 /UV process does not have the same limitations as that of H 2 O 2 /UV process. Many variables (temperature, pH, UV intensity, tubidity, lamp spectral characteristics, and pollutant type, etc.) affect the performance of the system [42,44].

Ozone/hydrogen peroxide/UV (O 3 /H 2 O 2 /UV) process
This method is considered to be the most effective and powerful method, which provides a fast and complete mineralization of pollutants [42,50]. The addition of H 2 O 2 to the O 3 /UV process accelerates the decomposition of ozone, which results in an increased rate of ·OH generation.
The main short mechanism of the O 3 /H 2 O 2 /UV process is given below: The capital and operating costs for the system vary widely depending on the wastewater flow rate, types, and concentrations of contaminants present and the degree of removal required [58].

Photo-Fenton process
The Photo-Fenton process occurs by the combination of H 2 O 2 and UV radiation with Fe(II) or Fe(III). The main factor of the mechanism is that iron salts act as photocatalysts and H 2 O 2 as an oxidizing agent. It offers a productive and cheap method for wastewater treatment and produces hydroxyl radicals to a greater extent [59].
The reaction is given below: A highly low reaction time is required for the photo-Fenton process, and depending on the operating pH value, the concentrations of H 2 O 2 and iron are added.

Heterogeneous photochemical oxidation processes
Widely investigated and applied heterogeneous photochemical oxidation processes are semiconductor-sensitized photochemical oxidation processes.
A semiconductor consists of two energy bands: one is high energy conduction and the other is low energy valence band. This kind of photolytic chemical oxidation is used for the generation of OH radical in heterogeneous processes. Zinc oxide, strontium titanium trioxide, and TiO 2 have been used for commercial implementation. Valance and conduction bands of a semiconductor material are distinguished by energy gap/band gap [60].
Moreover, the photocatalyst TiO 2 is a wide band gap semiconductor (3.2 eV) and is successfully used as a photocatalyst for the treatment of organic pollutants [61,62]. To summarize, in the TiO 2 process, the photon energy given to achieve the band gap energy and to induce an electron into the transmission band from the valence band can be fed with a wavelength shorter than 387.5 nm. Clarified reaction mechanisms of TiO 2 /UV process are given below [Eq. (16)- (19)].
The basic reason of this reversal is the production of photons. The reversal mechanism importantly decreases the photocatalytic efficiency of a semiconductor. Main benefit of TiO 2 /UV process is low energy consumption thus sunlight can be utilized as a light source [44].
AOPs have been examined in terms of limitations and summarized below.
As an example, UV oxidation process with H 2 O 2 is just effective at low wavelengths (especially under 200 nm).The treated aqueous flux must supply good transmission of UV light. Scavengers and high doses of chemical subscriptions may limit the process. Insoluble oil and grease, heavy metal ions, insoluble oil and grease, carbonates, and high alkalinity may cause clogging of the UV quartz handle. Air emission problems with O 3 may arise. The cost of the AOPs is expensive when compared to rival technologies [42].

Assessment of AOPs performance for antibiotic removal
Ozonation and AOPs are required for efficient degradation of antibiotics in water and wastewater. These treatment processes have an advantage of elimination of such pollutants through mineralization or conversion to the products that are less harmful to human health and the aquatic environment.
Various studies have published the effective AOPs treatment for the removal of antibiotics from wastewater [63][64][65][66][67]. High-quality and effective publications relevant with the AOP studies on the mechanisms and applications of water and wastewater treatments have been pronounced for last two decades. From the theoretical, environmental, and economical point of view, they demonstrate a great and increasing interest. As shown in Table 2, several studies have been conducted on the applicability of AOPs on different antibiotic classes.
Ozone is a potent oxidant and has been progressively applied for the treatment of wastewater.
Ozone and/or hydroxyl radicals passivate bactericidal characteristics of antibiotics by disrupting or modulating their pharmaceutically active functional groups, such as N-etheroxime and dimethylamino groups of macrolides [68,69], aniline moieties of sulfonamides [70], thioether groups of penicillins, unsaturated bonds of cephalosporin, and the phenol ring of trimethoprim [69]. High removal rates (>90%) were achieved by ozonation of the compounds with electron-rich aromatic systems, such as hydroxyl, amino (e.g., sulfamethoxazole), acylamino, alkoxy, and alkyl aromatic compounds, as well as those compounds with deprotonated amine (e.g., erythromycin, ofloxacin, and trimethoprim) and nonaromatic alkene groups, since these structural moieties are highly amendable to oxidative attack [1]. Ozonation process was found to be effective for the removal of b-lactams, macrolides, sulfonamides, trimethoprim, quinolones, tetracyclines, and lincosamides [5].
The performance of ozone treatment can be improved providing ozone is combined with UV irradiation, hydrogen peroxide, or catalysts such as iron or copper complexes [52]. Regardless, optimum process and operational circumstances have still been determined for the different water and wastewater types together with various types of antibiotics [152].
In general, Fenton process has been widely used successfully for the oxidation of many groups of antibiotics, including b-lactams, quinolones, trimethoprim, and tetracyclines. Fenton's oxidation is a homogeneous oxidation process and considered to be a metal-catalyzed oxidation reaction, in which iron acts as a catalyst [65,153]. The main handicap of the process is the low pH value. It is required to avoid iron precipitation that takes place at high pH [154,155].
Heterogeneous photocatalysis with TiO 2 semiconductor is generally accomplished by the illumination of a suspension of TiO 2 in aqueous solution with light energy which is greater than its bandgap energy. This causes the generation of high energy electron-hole pairs (e À /h þ ), which may migrate to the surface of the catalyst and may either reunite producing thermal energy or participate in redox reactions with the compounds that are adsorbed on the catalyst's surface [1].
Due to some disadvantages of the heterogeneous photocatalysis (e.g., rather small quantum efficiency of the process; comparatively narrow light-response reach of TiO 2 ; the requirement of postseparation and recovery of the catalyst particles from the reaction mixture in aqueous slurry systems), TiO 2 appear to have some interesting properties, such as high chemical stability in a wide pH range, strong resistance to chemical breakdown and photocorrosion, and high efficiency. The catalyst is also inexpensive and can be reprocessed [134,156]. The characteristics of antibiotics to be treated like pKa and molecular structure will identify not only the performance of their photocatalytic breakdown but also the mechanisms of the oxidation products formation.
Ultraviolet (UV) disinfection is progressively discovering practices in UWTPs. Photolytic breakdown can be either direct or indirect. In direct photolysis, the target pollutant assimilates a solar photon, which causes to a breakup of the molecule. In an indirect photolysis mechanism, as a matter of course occurring molecules in the system such as dissolved organic matter (DOM) behave as sensitizing species, which creates strong reactive agents such as hydroxyl radicals, singlet oxygen, and hydrate electrons under solar radiation [1,117].
Ultraviolet irradiation has been greatly used for the treatment of waters and wastewaters worldwide. Different studies have stated the effective treatment of UV irradiation for the removal of antibiotics in wastewater effluents [63]. It has been lately stated that at high UV doses of almost 11,000-30,000 mJ cm 2 , a nearly complete removal of tetracyclines and ciprofloxacin was obtained. Kim et al. [99] noticed that sulfonamides and quinolones demonstrate high removal efficiency in the reach of 86-100% throughout the UV process [1].
Many of the antibiotics have aromatic rings, structural moieties (such as phenol and nitro groups) heteroatoms, and other functional chromophore groups that can either absorb solar radiation or react with photogenerated transient species in natural. The organic material, UV dosage, contact time, and the chemical construction of the compound are significant agents ruling the removal performance of antibiotics throughout direct photolysis. This technique is only practicable to wastewater-containing photosensitive compounds and waters with low COD concentrations [5].
Most traditional operation performed in WWTPs and DWTPs (such as coagulation, flocculation, sedimentation, and filtration) were ineffective in the removal of these compounds [63], taking the improvement of new effective methodologies. Owing to the recalcitrant nature of the effluents including antibiotics residues, the implementation of the AOPs arises as an alternate. In fact, ozonation and Fenton's oxidation are the most tried methodologies. Although ozonation has the benefit of being used to fluctuate flow rates and compositions, the high cost of material and the energy required to provide the process constitute a primary disadvantage. Oxyhydroxides produce precipitate (if the pH range is not controlled well) when a homogeneous process is used and the necessity of recovering dissolved catalyst is a disadvantage. This is another process that is applied often to the group of beta-lactam antibiotics, combined with UV irradiation (photo-Fenton).

Conclusions
The consumption of antibiotics worldwide by human and veterinary uses has been increasing significantly. This is an important public concern because they have endocrine-disrupting properties even in trace concentrations and can cause microorganism resistance in aquatic environments. According to the researches made in recent years, advanced oxidation processes are promising treatment methods for the removal of the antibiotic compounds from water.
In the event of the photochemical technologies, we can determine that the photochemical AOPs are usually easy, clean, comparatively inexpensive, and productive against the classical, chemical AOPs. Four basic types of photochemical AOPs (H 2 O 2 /UV, O 3 /UV, H 2 O 2 /Fe 2þ /UV, and TiO 2 /UV) have been enforced to reduce and/or mineralize organic pollutants. We have defined that, within these photochemical processes, the photocatalytic ones had mainly a better performance.
Furthermore, it is significant to point that heterogeneous photocatalysis has been the aim of an enormous improvement in the last decade. In fact, TiO 2 is a semiconducter approach that exists, for example, as a chemically very stable, biologically inefficient, very easy to manufacture, cheaper than the photocatalytic viewpoint, active and several important photocalysts with an energy vacancy comparable to solar photons.