TiO2 photocatalysis under natural solar radiation for the degradation of the carbapenem antibiotics imipenem and meropenem in aqueous solutions at pilot plant scale

Water Research 166 (2019) 115037

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TiO2 photocatalysis under natural solar radiation for the degradation of the carbapenem antibiotics imipenem and meropenem in aqueous solutions at pilot plant scale Alejandro Cabrera-Reina a, Ana B. Martínez-Piernas b, Yannis Bertakis c,
Antonio Sa
nchez Pe
rez b, d Nikolaos P. Xekoukoulotakis c, *, Ana Agüera b, **, Jose
nica, Universidad de Tarapaca
, Av. General Vela
squez 1775, Arica, Chile EUDIM, Escuela Universitaria de Ingeniería Meca CIESOL, Joint Centre University of Almería-CIEMAT, Almería, Spain Department of Environmental Engineering, Technical University of Crete, Polytechneioupolis, GR-73100, Chania, Greece d Chemical Engineering Department, University of Almería, Spain a

b c

a r t i c l e i n f o

a b s t r a c t

Article history: Received 6 May 2019 Received in revised form 2 August 2019 Accepted 30 August 2019 Available online 31 August 2019

This paper deals with the removal of two last-resort antibiotics, namely imipenem and meropenem, in aqueous solutions employing heterogeneous photocatalysis with TiO2 under natural solar radiation at pilot plant scale. It was found that TiO2 photocatalysis is a very efficient technique for the degradation of both compounds in aqueous solutions, albeit it's relatively low quantum efficiency. At the experimental conditions employed in the present work (compound parabolic collectors photoreactor) the optimal TiO2 concentration was about 50 mg L
1. Experiments conducted in various aqueous matrices lead to the conclusion that the method can be applied to real aqueous matrices, such as natural waters and wastewaters. The comparison of TiO2 photocatalysis and natural photolysis showed an important decrease of the accumulated energy required to achieve the complete removal of both antibiotics which, in terms of normalized illumination time (t30W), represented a reduction of 50 min for imipenem and 60 min for meropenem. © 2019 Elsevier Ltd. All rights reserved.

Keywords: TiO2 Photocatalysis Aqueous matrices Carbapemen antibiotics Imipenem Meropenem

1. Introduction Antimicrobial resistance (AMR) has been detected in all parts of the world, and it is one of the most significant challenges to the global public health today (Davies and Davies, 2010; Laxminarayan et al., 2013; Holmes et al., 2016; O'Neill, 2016; Vikesland et al., 2017; WHO, 2019; EU, 2019; CDC, 2019). Moreover, the problem is increasing and is expected to have a severe impact on the public health in the near future. Indeed, according to the World Health Organization (WHO), the increasing resistance to antimicrobials is the most significant global concern for the public health, and WHO has highlighted the need for coordinated action to minimize the emergence and spread of AMR (WHO, 2019). In recent years, antimicrobial resistant bacteria are responsible for tens to hundreds of

* Corresponding author. ** Corresponding author. E-mail addresses: [email protected] (N.P. Xekoukoulotakis), [email protected] (A. Agüera). https://doi.org/10.1016/j.watres.2019.115037 0043-1354/© 2019 Elsevier Ltd. All rights reserved.

thousands of deaths in various parts of the world, including Europe (EU, 2019) and the USA (CDC, 2019), while if action is not taken, it is estimated that several million additional lives will be lost each year prematurely because of AMR (O'Neill, 2016; Kostyanev et al., 2019). Moreover, the costs associated with antibiotic-resistant infections exceed several billion euros and dollars per year in Europe and in the USA, respectively (Vikesland et al., 2017; EU, 2019; CDC, 2019). Because of the relatively rapid spread of antibiotic resistance, it has been expressed the fear that our globalized society is progressively entering a post-antibiotic era, and therefore measures should be taken to mitigate the spread of antibiotic resistance (Vikesland et al., 2017; WHO, 2019; EU, 2019; CDC, 2019). It should be noted that, although the development of antibiotic resistance is an ancient natural evolution phenomenon (D'Costa et al., 2011), its development and spread is being accelerated by different human factors, such as overuse and misuse of antimicrobial medicines in both human and veterinary medicine, inadequate or non-existent programs for infection prevention and control, poor-quality medication, weak laboratory capacity, inadequate surveillance and insufficient regulation of the use of antimicrobial drugs (WHO,

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2019; EU, 2019; CDC, 2019). Since antimicrobial resistant-microorganisms have been found in people, animals, food, and the environment (WHO, 2019), it has been widely understood that to combat the problem of AMR requires the systems thinking approach of the so-called “one-health perspective” (Vikesland et al., 2017; WHO, 2019; EU, 2019; CDC, 2019), according to which the environment, and in particular the aquatic environment, plays a very crucial role in the evolution and spread of AMR (Allen et al., 2010; Berendonk et al., 2015; Vikesland et al., 2017; WHO, 2019; EU, 2019; CDC, 2019). It has also been well established that sewage treatment plants (STPs) are hot spots for the development and spread of AMR, as well as for the release of antibiotics to the aquatic environment (Michael et al., 2013; Rizzo et al., 2013; Yang et al., 2017; Manaia et al., 2018; Tran et al., 2018; Danner et al., 2019), because conventional treatment methods applied to STPs are not effective for the removal of micropollutants, including antimicrobials, as well as antimicrobial resistant bacteria and genes. At this point, it should be emphasized that, one of the objectives of the so-called “One Health Action Plan” of the European Union against AMR is to support the development of various advanced treatment technologies that enable the efficient and rapid degradation of antimicrobials in wastewater and the environment, and thereby reduce the spread of AMR (EU, 2019). Antibiotic consumption has been recognized as one of the key drivers for the development and spread of antibiotic resistance. Indeed, it has been well established that there is a clear association between antibiotics consumption and the development and spread of antibiotic resistance, i.e., increased consumption of antibiotics results in increased antibiotic resistance levels (Bell et al., 2014; ECDC/EFSA/EMA, 2015; ECDC/EFSA/EMA, 2017; Chatterjee et al., 2018). In the past few decades, global antibiotic consumption, as well as antibiotic consumption rate, has been increased substantially (Van Boeckel et al., 2014; Klein et al., 2018; ResistanceMap, 2019). Moreover, the development of novel antibiotic is rather slow and therefore antibiotics are becoming a so called “endangered species” (Butler et al., 2017). However, although antimicrobial consumption is an important driver for increasing antimicrobial resistance levels, reduction of antimicrobial consumption will not be sufficient to effectively control the development and spread of antimicrobial resistance because the dominant contributing factor appears to be the spread of resistant strains and genes (Collignon et al., 2018). Therefore, additional measures should be taken to reduce antimicrobial resistance levels, including efficient water and wastewater treatment, among others (Collignon et al., 2018; EU, 2019). As a result of the increased consumption and use of antibiotics, their release into the aquatic environment has also been increased. Indeed, in recent years, antibiotics are considered as contaminants of emerging concern, due to their continuous input and persistence in the aquatic environment. Since the 1980s, several classes of antibiotics, including both human and veterinary antibiotics, have been identified in the aquatic environment at concentrations typically in the range from ng∙L
1 to mg∙L
1 (Hirsch et al., 1999; Kümmerer, 2009; Homem and Santos, 2011; Carvalho and Santos, 2016; Yang et al., 2017; Patel et al., 2019; Danner et al., 2019). Indeed, antibiotics have been identified all over the world and in almost any existing aquatic ecosystem, including lakes (Carvalho and Santos, 2016; Sousa et al., 2018; Yang et al., 2018), rivers (Carvalho and Santos, 2016; Desbiolles et al., 2018; Sousa et al., 2018), groundwater (Lapworth et al., 2012; Sui et al., 2015; Carvalho and Santos, 2016; Yang et al., 2017; Sousa et al., 2018), seawater (Alygizakis et al., 2016; Carvalho and Santos, 2016; Desbiolles et al., 2018), even drinking water (Yang et al., 2017). However, it has been found that the presence of antibiotics in the aquatic environment, even at such relatively low concentrations, is

capable of inducing the evolution of antibiotic resistance (Andersson and Hughes, 2014). Therefore, advance treatment methods should be applied for the efficient removal of antibiotics from the effluents of STPs, and consequently from the aquatic environment (EU, 2019). Among the various classes of antibiotics, in recent years, special emphasis has been given to carbapenem antibiotics (Papp-Wallace et al., 2011; Katzung, 2018). Carbapenems are synthetic b-lactam antibiotics that contain the characteristic four-membered 2azetidinone ring fused with a five-membered dihydropyrrole ring. Their mode of action against bacteria involves the inactivation of the terminal step of bacterial cell wall synthesis, and they have a wider spectrum of activity against bacteria in comparison with the typical b-lactam antibiotics, such as penicillins and cephalosporins. Therefore, they are considered one of the most reliable last-resort antibiotics used for the treatment against serious infections caused by Gram-negative bacteria. However, the emergence and spread of resistance mechanisms to carbapenems pose a major threat for infection control and treatment worldwide. Indeed, several carbapenem resistant bacteria and genes producing carbapemenases are increasingly being reported over the last two
n et al., 2012; Nordmann et al., decades (Walsh et al., 2005; Canto 2012; Albiger et al., 2015; Grundmann et al., 2017; Logan and € ro €k, 2018; Kostyanev et al., 2019). Weinstein, 2017; Wilson and To Carbapemenases are hydrolyzing b-lactam enzymes (i.e., b-lactamases) that facilitate the rapid addition of a water molecule across the b-lactam bond of the carbapemen antibiotics, thus rendering carbapenems ineffective against cell wall synthesis of the bacteria (Bush and Bradford, 2019). It should be noted that the WHO was requested by the Member States to develop a global priority pathogens list of antibioticresistant bacteria to help in prioritizing the research and development of new and effective antibiotic treatments. This list has been recently published, establishing a catalogue of 12 families of bacteria that pose the greatest threat to human health (WHO, 2017). Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae, which are carbapenem-resistant bacteria, are classified as critical in this list, i.e., with the highest priority. For example, according to the WHO, resistance in Klebsiella pneumoniae, which is a common intestinal bacterium that can cause life-threatening infections, to last-resort antibiotics, such as carbapenems, has spread to all regions of the world, and in some countries, carbapenem antibiotics do not work in more than half of people treated for K. pneumoniae infections (WHO, 2019). Of particular concern is the finding that, in recent years, the consumption of last-resort antibiotics, including carbapenems, has been rapidly increasing across all country income groups (Van Boeckel et al., 2014; Klein et al., 2018; ResistanceMap, 2019). In addition, increased consumption of carbapenem antibiotics has been associated with the emergence and spread of carbapenem € ro €k, 2018). Although, recently, some resistance (Wilson and To novel antibiotics are being developed, including combinations of blactam/b-lactamase inhibitors (Docquier and Mangani, 2018), and some other drug combinations (Tyers and Wright, 2019), as well as metallo-b-lactamase inhibitors (Wang et al., 2018), it is absolutely essential to preserve the efficacy of existing antibacterial drugs, such as carbapenems, as much as possible (Nordmann et al., 2012). Carbapenem antibiotics are excreted via the kidney (PappWallace et al., 2011; Katzung, 2018), so that they finally reach STPs, end eventually end-up in the aquatic environment. Indeed, recently, meropenem has been found in STPs influents and effluents (Tran et al., 2016a, 2016b; Le et al., 2018), and imipenem was found in hospital wastewater effluents (Szekeres et al., 2017), while in another recent study the concentration of imipenem in a hospital wastewater effluent was predicted to be in the order of a few

A. Cabrera-Reina et al. / Water Research 166 (2019) 115037

mg∙L
1 (Ory et al., 2019). As it was mentioned above, the prevention of these pharmaceuticals arriving surface water bodies is a key factor to control antibiotic resistance. In recent years, several advanced treatment methods have been successfully applied for the removal of various contaminants of emerging concern, including antibiotics, from aqueous matrices. Among these methods, special emphasis has been given to various advanced oxidation processes (AOPs), such as ozone oxidation, Fenton and photo-Fenton oxidation, heterogeneous photocatalysis, and UVC/H2O2, among others (Stefan, 2018). AOPs are oxidative techniques based on the intermediacy of various reactive oxygen species, such as hydroxyl radicals, HO (Stefan, 2018). Heterogeneous TiO2 photocatalysis is a mild oxidation technique which has been extensively studied in recent years for the elimination of various organic micro-pollutants in the aqueous phase, including pharmaceutical compounds, and in particular antibiotics (Michael et al., 2013; Kanakaraju et al., 2018; Stefan, 2018; Patel et al., 2019). In a previous study by our research group, we investigated the photochemical degradation of two representative carbapenem antibiotics, namely imipenem and meropenem, under solar radiation in aqueous solutions (Cabrera Reina et al., 2018). The aim of the present work was the application of solar TiO2 photocatalysis under natural solar radiation to remove imipenem and meropenem from water at low concentration and at pilot plant scale. The influence of catalyst load, as well as water matrix characteristics on treatment kinetics has been studied, and the corresponding photonic efficiencies have been calculated. Finally, normalized illumination times and energy requirements have been computed and compared with those of direct photolysis under natural solar radiation in the absence of TiO2. To the best of our knowledge, the photocatalytic degradation of the above carbapenem antibiotics has not been reported in the literature yet. 2. Materials and methods 2.1. Reagents, materials and aqueous matrices Imipenem monohydrate (C12H17N3O4S$H2O, 98), which was purchased from Sigma-Aldrich, and meropenem trihydrate (C17H25N3O5S$3H2O, 98.0e101.0%), which was purchased from Molekula, were both used as received. The chemical structures of both carbapenem antibiotics are shown in Fig. 1. Sulfuric acid (H2SO4, 95e97%) was obtained from J. T. Baker, while sodium hydroxide (NaOH, pellets) was obtained from Sigma-Aldrich. Heterogeneous photocatalytic experiments were carried out using slurry suspensions of Aeroxide P25 TiO2 (specific surface area 35e65 m2 g
1), kindly supplied by Evonik Industries.

3

The assays used to study the effect of catalyst concentration were carried out in ultrapure water, which was obtained from a Millipore water purification system (Milli-Q). Afterwards, the effect of water matrix was assessed using: (i) ultrapure water (UPW, initial pH 7.4); (ii) river water (RW, initial pH 8.5) and (iii) simulated WWTP effluent (WW, initial pH 7.7). River water was collected from the Andarax River when flowing close to the location of Padules (Almería, Spain). The constituents of the simulated WWTP effluent, each of them obtained from Sigma-Aldrich, are given in detail
nchez Pe
rez et al., 2017). The main general characelsewhere (Sa teristics of each aqueous matrix are given in Table 1. The initial concentration was 1.575 mmol L
1 (i.e., 500.0 mg L
1) and 0.114 mmol L
1 (i.e., 50.0 mg L
1) for imipenem and meropenem, respectively, so that these assays could be compared with existing photolysis experiments (Cabrera Reina et al., 2018). Aqueous solutions were prepared daily, just before the start of the decontamination assays, to avoid deviations of the initial concentrations. It should be highlighted that no organic solvents were used during the preparation of the aqueous solutions, because the presence of organic solvents may quench the various photo-generated chemical species (Li et al., 2017). 2.2. Solar irradiation experiments Heterogeneous photocatalytic experiments were carried out under natural solar radiation in a solar detoxification pilot plant, located in CIESOL (Solar Energy Research Center, Almería, Spain), based on compound parabolic collectors (CPC), as shown schematically in Fig. 2, and described in detail elsewhere (Cabrera Reina et al., 2018). Briefly, the CPC photoreactor consists of two twin glass tubes fitted onto the focus of two CPC mirrors, and the whole system is fitted on a platform. Modules are facing south and tilted 37 (local latitude) to maximize annual energy collection. The total illuminated surface of each photoreactor is 0.42 m2, while the total and the illuminated volume are V ¼ 7 L and Vi ¼ 4.77 L, respectively. Experiments were carried out in batch mode during which the aqueous solutions were recirculated through the photoreactors by means of a centrifugal pump. The incident fluence rate in the UVA region of the electromagnetic spectrum, Eo (in W∙m
2), defined as the radiant power in the UVA region incident from all directions onto a small sphere divided by the cross-sectional area of that sphere (Braslavsky, 2007) was monitored employing a Delta Ohm UV radiometer (LP UVA 02 AV, spectral response range from 327 nm to 384 nm) also mounted on the platform and tilted at 37. It should be noted that the efficiency of a natural solar reactor depends on the solar radiant power absorbed by the reaction system, and therefore on the incident solar radiant power.

Fig. 1. Chemical structures of imipenem monohydrate and meropenem trihydrate. The ionization constants, pKa, of both compounds were obtained from the Advanced Chemistry Development (ACD/Labs) software (ACD/Labs, I-Lab 2.0, https://ilab.acdlabs.com/iLab2/). Acidic hydrogen atoms are marked in red. (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

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Table 1 Composition of the aqueous matrices used in the present work. Variable

River Water

Simulated MWWTP effluent

Ultrapure Water

Total Organic Carbon (TOC), in mg∙L
1 Inorganic Carbon (IC), in mg∙L
1 Total Carbon (TC), in mg∙L
1 [F
], in mg∙L
1 [Cl
], in mg∙L
1
1 [NO
2 ], in mg∙L
1 [NO
3 ], in mg∙L
1 [PO3
], in mg∙L 4
1 [SO2
4 ], in mg∙L pH

15.1 53.1 68.1 0.4 16.5 0.9 5.0 0.3 209.3 8.5

7.9 5.7 13.6 0 50.2 0 1.3 0.2 239.6 7.7

e e e e 1 e e e e 7.4

by the cross-sectional area of the sphere and per time interval (in mol∙m
2 min
1 or einstein∙m
2 min
1) (Bolton and Stefan, 2002; Braslavsky, 2007); S is the surface area of the photochemical reactor exposed to radiation (in m2); and V is the total volume of the photochemical reactor (in L). The incident photon fluence rate, E0n;p;o , was calculated as described in detail in our previous work (Cabrera Reina et al., 2018). The incident UVA fluence rate, Eo, was used to calculate the accumulated energy per volume needed to reach a particular degradation level, QUV, (in J∙L
1) according to the following equation: QUV,n ¼ QUV,n
1 þ Eo,aver,n(S/V)Dt; Dt ¼ tn
tn
1

Fig. 2. Experimental setup under natural solar radiation: outdoors solar detoxification pilot plant with compound parabolic collectors (CPC).

Consequently, the direct comparison between experiments in terms of treatment time is appropriate only if these experiments are carried out in identical systems and simultaneously. Therefore, as it was mentioned in our previous work (Cabrera Reina et al., 2018), experiments under natural solar radiation were carried out either in parallel or on successive days at about the same times. Consequently, the average UVA fluence rate of each experimental run did not differ significantly from one experiment to the other, thus allowing their direct comparison in terms of treatment time. In a typical experimental run, TiO2 was loaded in the recirculation tanks of the CPC system at the desired initial concentration, and the resulting aqueous suspensions were recirculated in the dark for 15 min before uncovering the CPC system. Samples periodically taken from the photochemical reactor were centrifuged to remove suspended TiO2 particles, and then analyzed for residual carbapenems concentration. Control experiments were performed for evaluating antibiotics adsorption onto the catalyst surface under the same initial conditions used in the photocatalytic experiments. The results showed, approximately, a 10% adsorption for all the evaluated catalyst concentrations (i.e. 10, 20, 50 and 100 mg L
1). For each experimental run, the flow of incident radiation on the photochemical reactor in the wavelength range from 300 to 400 nm, I0(l) (in mol∙L
1 min
1 or einstein∙L
1 min
1), was calculated according to the following equation:

I0 ðlÞ ¼ E0n;p;o ðS=VÞ

(1)

where E0n;p;o is the incident photon fluence rate on a chemical amount basis, defined as the total number of moles of photons (i.e., einsteins) incident from all directions onto a small sphere, divided

(2)

where QUV,n
1 is the energy accumulated up to the start of the current time period; tn and tn
1 is the experimental time (in s) for the samples n and n
1, respectively; Eo,aver,n is the average UVA fluence rate (in W∙m
2) between tn and tn
1; S is the surface area of the photochemical reactor exposed to radiation (in m2); and V is the total volume of the photochemical reactor (in L). Moreover, the normalized illumination time t30W (in s), which is another comparison tool that represents the treatment time if the assay would have been carried out under constant solar radiation of 30 W m
2, was calculated using the following equation (Malato et al., 2003):

t30W;n ¼ t30W;n
1 þ Dtn

Eo;aver;n Vi 30 V

(3)

where t30W,n is the normalized illumination time; t30W,n
1 is the normalized illumination time up to the start of the current time period; V and Vi represent the total and the illuminated volume of the photoreactor, respectively (both in L). 2.3. Analytical measurements Analytical measurements to determine carbapenems degradation profiles were carried out in an HPLC system equipped with a ZORBAX ECLIPSE XDB-C18 analytical column (1.8 mm, 4.6  50 mm; Agilent), and coupled with a UV detector (Series 1200, Agilent Technologies). Further details about the analytical method can be found elsewhere (Cabrera Reina et al., 2018). 3. Results and discussion 3.1. TiO2-assisted photocatalytic degradation under solar irradiation The heterogeneous photocatalytic degradation of imipenem and meropenem was studied in aqueous solutions in UPW under natural solar radiation in the presence of TiO2 (Aeroxide P25).

A. Cabrera-Reina et al. / Water Research 166 (2019) 115037

Experiments were conducted in the CPC system in the presence of 10 mg L
1 TiO2, at inherent solution pH (in the presence of 10 mg L
1 TiO2, inherent solution pH was approximately 6.6), while the initial concentration of imipenem and meropenem was 1.575 mmol L
1 (i.e., 500.0 mg L
1) and 0.114 mmol L
1 (i.e., 50.0 mg L
1), respectively. As can be seen in Fig. 3, the degradation of both compounds upon solar irradiation in the presence of TiO2 proceeded relatively fast. For example, the removal of imipenem was approximately 75% after 60 min solar irradiation in the presence of TiO2, while the degradation of meropenem was slightly faster, and about the same percentage of decay (i.e., 75%) was achieved after 45 min irradiation. Moreover, the photochemical degradation of both compounds under natural solar radiation in the presence of TiO2 was much faster than in the corresponding direct photolysis experiments (for comparison reasons, the photochemical degradation of both compounds under natural solar radiation is shown in Fig. S1 in the supplementary materials, as it was published in our previous work (Cabrera Reina et al., 2018). Additional experiments were carried out to assess the degree of mineralization, as described in detail in Section S1 in the supplementary materials. It was found that after prolonged irradiation the degree of mineralization was rather low, thus indicating that some rather stable transformation products were formed. Τhere are two mechanisms which contribute simultaneously to the photochemical degradation of both compounds, namely: (i) direct photolysis under solar radiation, as described in detail in our previous work (Cabrera Reina et al., 2018); and (ii) photocatalytic degradation, which takes place through various intermediate reactive chemical species, generated upon illumination of TiO2 in aqueous suspensions. The detailed mechanism of the photocatalytic degradation of organic pollutants upon irradiation of aqueous TiO2 suspensions has been discussed extensively in the scientific literature (Stefan, 2018; Schneider et al., 2014; Hoffman et al., 1995). Very briefly, upon illumination of aqueous TiO2 suspensions with irradiation energy equal to or greater than the band gap energy of the semiconductor, valence band holes, and conduction band electrons are generated. These photogenerated chemical species can either recombine to liberate heat or make their separate ways to the surface of TiO2, where they can react with species adsorbed onto the catalyst surface, thus leading to

5

various reactive oxygen species, including hydroxyl radicals (Stefan, 2018; Schneider et al., 2014; Hoffman et al., 1995). These reactive oxygen species, as well as the photogenerated valence band holes, can oxidize most of the organic pollutants commonly found in water and wastewaters, including pharmaceutical compounds (Kanakaraju et al., 2018; Patel et al., 2019). Overall, these two mechanisms, i.e., direct photolysis under solar radiation and photocatalytic degradation in the presence of TiO2, contribute to accelerating the photochemical degradation of both carbapenem antibiotics significantly.

3.2. Effect of TiO2 concentration The concentration of TiO2 in slurry photocatalytic processes is an important factor that can influence the degradation of the organic pollutants strongly (Herrmann, 2010). Indeed, several studies have indicated that the rate of the heterogeneous photocatalytic degradation of various organic pollutants in aqueous solutions initially increases with increasing catalyst loading and then usually reaches a plateau at higher catalyst concentration, or even decreases at excessive catalyst loadings, because of radiation scattering and screening effects (Kisch and Bahnemann, 2015; Herrmann, 2010). Therefore, due to its significance, the effect of TiO2 loading on the photocatalytic degradation of imipenem and meropenem was investigated in aqueous solutions in UPW under natural solar radiation in the presence of various concentrations of TiO2. Experiments were conducted in the CPC system by varying TiO2 loading in the range from 10 to 100 mg L
1, at inherent solution pH (in the presence of higher concentrations of TiO2, such as 50 and 100 mg L
1, inherent solution pH was approximately 5.5). The initial concentration of imipenem and meropenem was 1.575 mmol L
1 (i.e., 500.0 mg L
1) and 0.114 mmol L
1 (i.e., 50.0 mg L
1), respectively, and the results are also shown in Fig. 3. Moreover, for each experimental run, the pseudo-first order rate constants of the photocatalytic degradation of both compounds were calculated, and then the initial reaction rates, r0 (in mol∙L
1 min
1), have been computed by multiplying the pseudofirst order rate constants with the initial concentration of each compound. The results are shown in Table 2, while Fig. 4 shows the

Fig. 3. Effect of TiO2 concentration on the photocatalytic degradation of (a) imipenem and (b) meropenem in UPW at inherent solution pH under natural solar radiation. Experimental conditions: [imipenem]0 ¼ 1.575 mmol L
1 (i.e., 500.0 mg L
1); [meropenem]0 ¼ 0.114 mmol L
1 (i.e., 50.0 mg L
1). Experiments were conducted at the CPC system. The inset figures show the plot of eln(C/C0) versus time for each experimental run.

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A. Cabrera-Reina et al. / Water Research 166 (2019) 115037

Table 2 Initial reaction rate, r0 (in nmol∙L
1 min
1), and photonic efficiency, zp (in mol∙einstein
1), of the photocatalytic degradation of imipenem and meropenem in aqueous TiO2 suspensions in UPW, in RW and in WW, under natural solar radiation. [TiO2] (mg∙L
1)

10 20 50 100 50 50

Water matrix

UPW UPW UPW UPW RW WW

Imipenem

Meropenem

r0 (nmol∙L
1 min
1)

zp  105 (mol∙einsten
1)

r0 (nmol∙L
1 min
1)

zp  106 (mol∙einsten
1)

39.2 50.9 78.0 83.0 47.8 43.1

4.5 5.8 8.7 9.3 5.0 4.5

3.50 4.59 6.53 6.75 4.90 4.95

3.9 5.2 7.3 7.6 5.3 5.3

Fig. 4. Effect of TiO2 concentration on the initial reaction rates, r0 (in nmol∙L
1 min
1), and photonic efficiency, zp (in mol∙einstein
1), of the photocatalytic degradation of (a) imipenem and (b) meropenem under natural solar radiation. Experiments were conducted at the CPC system. Dashed lines are plotted to guide the eye.

plot of the initial reaction rate of each compound as a function of catalyst concentration. As can be seen, the initial reaction rates of the photocatalytic degradation of both compounds increased with increasing catalyst concentration up to approximately 50 mg L
1, after which r0 remained practically constant. The increase in photocatalytic reaction rate with increasing catalyst loading indicates a heterogeneous catalytic regime, since the fraction of incident radiation absorbed by the semiconductor progressively increases in suspensions containing higher amounts of TiO2 (Herrmann, 2010). However, the initial reaction rates of the photocatalytic degradation of both compounds reached a plateau at about 50 mg L
1 TiO2 loading. The catalyst concentration above which reaction rate levels off depends on several factors (such as reactor geometry, substrate concentration, wavelength and intensity of radiation source) and corresponds to the point where all catalyst particles, i.e., all the surface exposed, are fully illuminated (Herrmann, 2010). At higher concentrations, a screening effect of excess particles occurs, thus masking part of the photosensitive surface and consequently hindering radiation penetration, and as a result, the initial reaction rate reaches a plateau, as can be seen in Fig. 4. In this study, the optimal initial reaction rate was 78.0 and 6.53 nmol L
1 min
1, for imipenem and meropenem, respectively, while the optimal TiO2 concentration at which subsequent photocatalytic experiments were conducted was about 50 mg L
1. At this point, it should be emphasized that the optimal initial reaction rate and the optimal TiO2 concentration depend on the absorbed radiation intensity and the geometry of the photocatalytic reactor (Kisch and Bahnemann, 2015). Moreover, the optimum photocatalyst loading is also determined by the concentration of the target pollutants in the aqueous matrix. Indeed, treatment of industrial wastewater, where the concentrations of the target pollutants are in the order of mg∙L
1, usually several hundreds of

mg∙L
1 of the photocatalyst are required. On the other hand, the removal of contaminants of emerging concern, which are present in the aqueous matrix at the sub-mg∙L
1 level, can be achieved with substantially lower TiO2 concentrations (Prieto-Rodriguez et al., 2012). Consequently, very different concentrations of TiO2 have been reported as optimum values. For example, Kaneco et al. (2009) studied the removal of thiram at an initial concentration of 5 mg L
1 in a Pyrex reaction vessel (100 mL) finding the best degradation rates when using 8 mg L
1 of TiO2, while Minero et al. (1996) recommended 200 mg L
1 of TiO2 for treating pentachlorophenol in a Helioman reactor. Therefore, the optimal photocatalyst concentration has to be determined in each particular case. As far as the energy requirements are concerned, the use of heterogeneous photocatalysis decreased the solar energy required to bring about the degradation of both compounds, with respect to natural photolysis. More specifically, the QUV needed to achieve over 80% removal of imipenem and meropenem using 50 mg L
1 of TiO2 was approximately 2.2 kJ L
1, while this value increased to approximately 8.7 kJ L
1, when the experiment was carried out under natural solar radiation in the absence of TiO2. In terms of the normalized illumination time, t30W, imipenem and meropenem can be removed after 46 min and 49 min, respectively, when using heterogeneous photocatalysis, while these values increased to 98 min and 105 min, respectively, under natural solar radiation in the absence of TiO2. Thus, the energies and treatment times needed to degrade both antibiotics in aqueous solutions were substantially decreased in the presence of TiO2 under natural solar radiation. 3.3. Apparent quantum yield or photonic efficiency As have been discussed in detail in the literature (Kisch and Bahnemann, 2015), measuring the quantum yield of a

A. Cabrera-Reina et al. / Water Research 166 (2019) 115037

photocatalytic process requires measuring the intensity of the radiation absorbed by the photocatalyst. Unfortunately, this measurement is difficult for a heterogeneous system, since it should be taken into account not only the absorption of radiation by the photocatalyst but also scattering and reflection of radiation by the suspended particles of the photocatalyst (Kisch and Bahnemann, 2015). Therefore, to overcome this problem, several approaches have been proposed, including measuring the so-called apparent quantum yield or photonic efficiency, zp(l), (dimensionless or mol∙einstein
1) of the photocatalytic process, according to the following equation (Kisch and Bahnemann, 2015):

zp ðlÞ ¼

r0 I0 ðlÞ

7

imipenem and meropenem, respectively. These values are very low mainly for two reasons: (i) as mentioned above, in the calculation of the photonic efficiencies we didn't take into account losses of radiation due to reflection and scattering of incident radiation, which has been reported to range from 13% to 76% of the total incident photon flux (Kisch and Bahnemann, 2015); and (ii) it is well known in the literature that the main process which takes place after the photochemical generation of valence band holes and conduction band electrons is their recombination to liberate heat, either in the bulk or on the surface of the photocatalyst (Schneider et al., 2014; Hoffman et al., 1995), thus reducing the apparent quantum yield of the process substantially.

(4)

where r0 is the initial rate of the photocatalytic reaction (in mol∙L
1 min
1), and I0(l) is the flow of incident radiation on the photochemical reactor in the wavelength range from 300 to 400 nm (in mol∙L
1 min
1 or einstein∙L
1 min
1). It should be noted that comparing photonic efficiencies is only possible if radiation absorption is the same in each experimental run, and this is rather unlikely to occur in different photochemical reactors (Kisch and Bahnemann, 2015). However, if the experiments are carried out in the same photochemical reactor and at catalyst concentrations which do not differ significantly between them, it is likely that radiation absorption is the same for all experimental runs. In the present work, the above assumption was considered to be valid, since the experiments were carried out in the same photochemical reactor at various catalyst concentrations which did not differ substantially between them. In addition, it should be emphasized once more that at the experiments conducted at different TiO2 concentrations, the average UVA irradiance of each experimental run did not differ significantly from one experiment to the other. Based on the above, the photonic efficiencies of the photocatalytic degradation of imipenem and meropenem were calculated, and the results are given in Fig. 4 and Table 2. As expected, the photonic efficiencies of the photocatalytic degradation of both compounds follow the same trend as the initial reaction rate. The photonic efficiency at the optimal TiO2 concentration (i.e., 50 mg L
1 TiO2) was 8.7  10
5 and 7.3  10
6 mol E
1 for

3.4. Effect of the water matrix In a final set of photocatalysis experiments, the effect of the water matrix was studied. Therefore, additional photocatalysis experiments were carried out in two aqueous matrices, namely in river water (RW) and in simulated MWWTP effluent (WW) and the results were compared with those obtained in UPW. Experiments were conducted in the CPC system at an initial concentration of 1.260 mmol L
1 (i.e., 400.0 mg L
1) and 0.114 mmol L
1 (i.e., 50.0 mg L
1) for imipenem and meropenem, respectively, and at 50 mg L
1 TiO2 loading. This concentration was selected based on the above-mentioned results of the TiO2 load experimental series. The results are shown in Fig. 5, while the initial reaction rates and the corresponding photonic efficiencies for both compounds are given in Table 2. As can be seen, the initial reaction rates and the corresponding photonic efficiencies were slightly decreased when the experiments were carried out in WW and RW. This reduction in the photocatalytic activity was obviously due to the consumption of the various photogenerated reactive chemical species formed upon irradiation of the aqueous TiO2 suspensions by the various organic and inorganic components of the aqueous matrices. More specifically, for imipenem, the initial reaction rate decreased from 78.0 to 83.0 nmol L
1 min
1, which were the values obtained in ultrapure water with 50 and 100 mg L
1 of TiO2, respectively, to 47.8 and 43.1 nmol L
1 min
1, which were the values obtained in river water and simulated WWTP effluent, respectively. In addition, for

Fig. 5. Effect of water matrix on the photocatalytic degradation of (a) imipenem and (b) meropenem under natural solar radiation. Water matrices: UPW (pH ¼ 7.4); WW: simulated MWWTP effluent (pH ¼ 7.7); RW: river water (pH ¼ 8.5). Experimental conditions: [TiO2] ¼ 50 mg L
1, [imipenem]0 ¼ 1.260 mmol L
1 (i.e., 400.0 mg L
1); [meropenem]0 ¼ 0.114 mmol L
1 (i.e., 50.0 mg L
1). Experiments were conducted at the CPC system. The inset figures show the plot of eln(C/C0) versus time for each experimental run.

8

A. Cabrera-Reina et al. / Water Research 166 (2019) 115037

meropenem, the initial reaction rate decreased from 6.53 to 6.75 nmol L
1 min
1 to 4.90 and 4.95 nmol L
1 min
1, respectively. For both compounds, the results obtained in RW as well as in simulated WWTP effluent using 50 mg L
1 of TiO2 were similar to those obtained in UPW using 20 mg L
1 of TiO2. From the above results, it can be concluded that the reduction in the photocatalytic efficiency for the experiments carried out in RW and simulated WWTP effluent was rather small to insignificant, which means that photocatalysis can be applied to real aqueous matrices, such as natural waters and wastewaters, without any significant reduction in the photocatalytic activity. As occurred in ultrapure water, in terms of the energy requirements, heterogeneous photocatalysis improved treatment efficiency with respect to natural photolysis. More specifically, for the photocatalytic degradation of imipenem in the presence of 50 mg L
1 TiO2 in simulated WWTP effluent and RW, the QUV needed to achieve over 80% reduction was approximately 3.3 kJ L
1, while for meropenem the QUV needed to achieve over 70% reduction was approximately 2.2 kJ L
1.

 The experiments were carried out under natural radiation, but also at a pilot plant scale, while the photoreactor used is available in just a few research groups.  The operation conditions employed are close to actual situations, while the selected initial concentrations of both compounds are environmentally relevant.  Advanced analytical methods have been employed.  Apparent quantum yields have been determined. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Acknowledgements The authors would like to acknowledge the SFERA-II Programme for financial support. Alejandro Cabrera Reina wishes to thank FONDAP/15110019 and FONDECYT/11160680.

4. Conclusions and added value The conclusions drawn for the present study can be summarized as follows:  Heterogeneous TiO2 photocatalysis is a very efficient technique for the degradation of imipenem and meropenem antibiotics in aqueous solutions under natural solar radiation.  The degradation of both compounds in aqueous solutions upon solar irradiation in the presence of TiO2 proceeded much faster than during photolysis and the energy requirements were decreased approximately by half.  At the experimental conditions employed in the present work, the optimum TiO2 concentration for the photocatalytic degradation of both compounds upon illumination with solar radiation in aqueous solutions in ultrapure water was 50 mg L
1.  The photonic efficiencies of the photocatalytic degradation of both compounds in aqueous solutions under solar radiation and at the optimal TiO2 concentration were in the order of 10
5 to 10
6 mol E
1. These rather low values can be attributed to losses of radiation due to reflection and scattering of incident radiation, as well as due to the recombination of the photo-generated valence band holes and conduction band electrons of TiO2.  The initial reaction rates and the corresponding photonic efficiencies were decreased when the experiments were carried out in simulated WWTP effluent and river water. This reduction in the photocatalytic activity was obviously due to the consumption of the various photogenerated reactive chemical species formed upon irradiation of the aqueous TiO2 suspensions by the various organic and inorganic components of the aqueous matrices. The results obtained both in river water and simulated WWTP effluent using 50 mg L
1 of TiO2 were similar to those obtained with 20 mg L
1 of TiO2 in ultrapure water. Moreover, the added value and the originality of our work can be summarized as follows:  The fate of the carbapenem antibiotics in the environment is critical. Indeed, carbapenems are of particular interest since they belong to the group of last-resort antibiotics. Therefore, it is essential to gather information about possible treatment methods aiming at their elimination from aqueous matrices.  To the best of our knowledge, the photocatalytic degradation of the target carbapenem antibiotics has not been reported in the literature yet.

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