Introduction

A concernabout the presence of emerging pollutants in wastewater, has increased in recent years, due to the potential unfavorable consequences to human health; among these, several classifications are presented, one of them being pharmaceutical products comprising of antibiotics, analgesics, antidepressants, among others [1]. Antibiotics are compounds used in humans and animals to treat infectious diseases; however, in recent decades these compounds have been used excessively, whose presence has increased in wastewater, with alterations of the aquatic environment, increased risks to human health, geno-toxic effects and the development and proliferation of bacteria which is resistant to antibiotics (ARB). The ARB are microorganisms that resist the antibiotic effects and their antibiotic resistance genes (ARG) can be transferred from one bacterium to another and contain the genetic coding that makes them resistant [2]. In that sense, , the World Health Organization (WHO) has classified the bacterial resistance phenomenon as a global emergency [3]. Due to the public health problems that it causes, there is a reduction in the effectiveness of medical treatments against diseases, the increase in morbidity and mortality, that is reflected in 25000 annual deaths in Europe and 19000 in the United States, as well as the increase in costs for medical care and the time required for treatment [4].

Among the countries with the highest rate of antibiotic use are: Turkey, Tunisia and Spain, with a defined daily dose (DDD) per 1000 inhabitants of 48.1, 47.8 and 40.1 respectively [5], as well as China which also positioned itself as the largest producer of antibiotics. In 2013, this country used about 162,000 tons of them [6]. On the other hand, Latin American countries such as Brazil, Cuba, Ecuador, Uruguay, Venezuela, Dominican Republic, Mexico, Peru and Colombia, have a consumption lesser than 20 DDD per 1000 inhabitants. This value is below 50% compared to the values registered by the aforementioned countries of Europe and Africa. Colombia has an average rate of 8.1 DDD per 1000 population [4]; considering that in outpatient prescriptions and highly complex treatments, there are doses of 1.58 and 22.5 [7], [8]. However, 34.6% of antibiotic prescriptions correspond to inappropriate use, which contributes to the problem as described previously [9].

It is important to make emphasis that once antibiotics are ingested undermedical prescription, they are eliminated through urine and human feces, reaching the bodies of water, although it is possible that they reach them by simple contact with the environment, which generates their presence in wastewater [6]. In this resource, the transfer of ARG (causes of antibiotic resistance) is possible, due to the deposition of different bacteria that already developed resistant genes and others that come from different tributaries, such as urban wastewater and livestock [10]. It has been found that human feces have the presence of β-lactam antibiotics and sulfonamides, with values of 10.86 μg / kg and 8.2μg / kg, respectively [6].

Therefore, the treatment of wastewater is a determining factor in the distribution of these emerging pollutants, which in global terms includes central urban waters centralized treatment systems deploying primary treatment; and in some cases secondary treatment. According to the global wastewater treatment indicator, which was developed in 2017 by members of Yale University and the Columbia University Land Institute, the highest water treatment levels are centered in Europe and the lowest ones correspond to Latin America and the Caribbean, sub-Saharan Africa and South Asia [11].

As a result of the low treatment levels, in New Mexico, the United States and there Czech Republic, were found antibiotic concentrations such as norfloxacin, ciprofloxacin and sulfamethoxazole, were found in the effluent of a Wastewater Treatment Plants (WWTP). Only 40 to 86% of antibiotics are eliminated in the case of the Czech Republic and 20 to 77% in New Mexico [12],[13]. In addition, in Sfax, Tunisia (considered the second country consuming the most number of antibiotics [5]) 13 antibiotics were present in both, the tributary and the effluent, since the highest removal obtained in the plant was 88% for trimethoprim and less than 33% for sulfapyridine [14]. In Latin America, the presence of azithromycin, ciprofloxacin, clarithromycin, norfloxacin and sulfamethoxazole is found in tributaries and effluents of two WWTP, one in Medellin and the other one in Bogotá, Colombia [15].

Despite the available information and advanced techniques, a study that included the removal of antibiotics, ARB and ARG in parallel, was not found among the references consulted. That is why, given the need to mitigate the risk of exposure in water sources, this review is carried out based on the analysis of 9 technologies used in different countries for the removal of antibiotics, ARB and ARG, each with their respective modifications and innovation of conventional processes, to obtain better efficiencies. Among the 9 technologies 8 are advanced oxidation processes, membrane bio-reaction and absorption with activated carbon, due to the removal efficiencies, obtained through them and their constant research. In the development of this review, the removal efficiency of each technology was analyzed, according to the research carried out on them, as well as their influence on the countries where they have been implemented.

Materials and methods

This document outlines a systematic review of the technologies applied around the world, for the removal of antibiotics from wastewater, along with resistant bacteria and their genes. This was possible by the means of searching for research and review articles in which the broadest and most relevant issues of the problem were identified, in order to understand its scope and the importance of its management.

Due to its high application potential and removal efficiencies that change depending on the technology during the preliminary search, it was possible to identify the implementation of tertiary treatments for the removal of antibiotics ARG, and ARB, such as advanced oxidation, membrane filtration, and adsorption processes [16]. These processes increase the efficiency of conventional treatments during the removal of contaminants, to reach the limits defined by the regulation [16]. In the same way, membrane filtration and adsorption processes, due to its high application potential and removal efficiencies, differ depending on the technology [17]. Once the removal technologies were identified, their search was carried out by considering in each case the following keywords: “Degradation of antibiotics by ozone”, “Removal of antibiotic resistance genes by ozone”, and “Removal of bacteria resistant to antibiotics by ozone”. The search was carried out in the ScienceDirect and Scopus databases bytaking into account only experimental researches (but literature reviews), in which the removal of each contaminant was evidenced and were in a range of 2006 and 2019. Besides, to make a comparison between the best methodologies in terms of the removal of the studied contaminants, the researches with the highest removal rates (> 70%) were selected. However, due to the implementation of conventional methodologies (without variations or additional ones ), few results are presented with lower efficiency, this to show the considerable improvement of this variable, through process innovation. About the inclusion criterion mentioned, no research was rejected due to the nature of their scale; more than 75% of research belongs to tests carried out in the laboratory, and the remaining percentage corresponds to real and pilot size scales.

During the systematic review, 47 researches of 66, which were examined, were extracted; however, the review articles, as well as other documents, were considered and used to discuss the obtained results.

All information was written on a basis that contemplated the following fields: title of the article, author (s), year of publication, journal, country, type of research, its purpose, place where it was developed, methodology implemented and finally its results and discussion. A quantitative analysis of the information was carried out according to the number of publications per country, and the efficiency of each technology in the removal of contaminants.

Advanced oxidation processes

Advanced oxidation (AO) processes, in addition to removing other compounds, facilitate the removal of antibiotics from wastewater. These provide high efficiency due to the high oxidation potentials, which destabilize certain bonds, thus generating less harmful materials. Within these processes are ozonation, Fenton oxidation, photo-catalysis, electro-chemistry, UV radiation and gamma radiation. Below is a brief description of each case.

Ozonation

Ozonation belongs to AO technologies, within non-photochemical processes, and is used in wastewater to oxidize contaminants [18]. The ozone has two ways to react with pollutants; one by direct reaction and the other one by means of free radicals that are formed during the decomposition of ozone in water (indirect) [19]. Hydroxyl radicals are produced through free radicals, which are highly reactive and lead to the degradation of pollutants, when are attacked by ozone molecules [20].

The focus on the removal of antibiotics using this technology began in 2005. According to the review carried out, this technology has efficiencies greater than 84%; in addition, it shows the interest of countries such as Germany to eliminate antibiotic resistance genes from the waters, since these are transmitted horizontally from one bacterium to another one increasing the public health problem. Table 1 presents the results of research conducted in three different countries where the target pollutants are mainly ARG and some antibiotics.

Table 1 presents the research related to technology, detailing in the first column the country where it was carried out, and in the second, the antibiotic, ARG, or ARB removed of the wastewater. The third column details the type of sample studied, in the fourth, the pollutant removal efficiency, and in the fifth column, the methodology used in the research is provided.

The WEDECO system is used for high continuous oxygen production through a low energy consumption compared with a conventional generator since it produces up to 9% more ozone in its efficient line and 4% in its standard line, with the same consumption [26]. Additionally, there are removal efficiencies in logarithmic units (log), where 3.7 log is equivalent to a reduction greater than 99.9%.

Fenton

This AO process is carried out through the use of hydrogen peroxide (H₂O₂) and a transition metal as a catalyst, generating chain reactions that allow the H₂O₂ to be consumed; thus a hydroxyl radical is produced, which is capable of removing substances quickly [27]. Additionally, one of AO process advantages is the easy use, the low cost of its usage and the fact that it does not represent a threat to the environment [28]. This process has been implemented since 1984 with more than 344 publications to current date; and 21% of this have been published in 2019.

Fenton oxidation achieves better removal results when supplemented with other methods (see Table 2). However, the best efficiencies are obtained by implementing photo-fenton in an antibiotic solution, since it achieves better results in less time, converting this into greater efficiency within a WWTP, due to the possibility of treating a high flow rate in a short time.

Photocatalysis

Photocatalytic oxidation or photocatalysis has been the subject of more than 654 research papers in recent decades, which increased exponentially in 2014 according to Scopus analysis. This process is based on the adsorption of light by a material used as a photocatalyst, which generates electron-hole pair, and these, in turn, hydroxyl radicals that lead to the degradation of pollutants [35]. Titanium dioxide (TiO₂) is the most researched and tested photocatalyst in studies conducted with this treatment [36]. It is emphasized that despite being considered a promising treatment, the results of the registered research do not show high removal efficiencies for some antibiotics such as erythromycin and clarithromycin (see Table 3); the same goes for Escherichia coli HB101. However, it is noticedthat in China the implementation of photocatalysis for the removal of ARB and ARG, showed important results, where a 99% removal efficiency for genes was achieved ampC, mecA, and the bacteria Staphylococcus, Pseudomonas aeruginosa.

Ultrasound

In the implementation of ultrasound, degradation of contaminants is performed by acoustic cavitation. In this phenomenon micro-bubbles filled with gas or steam, are formed by acoustic waves that are introduced into a liquid body. Thanks to the high pressure and temperature conditions within the microbubbles (which can reach 5000 ° C and 1000 bar), the water molecules decompose generating H+ and OH- radicals, which lead to the degradation of pollutants [42]. Among the advantages of this method, the treatment in ambient conditions of temperature and pressure can be mentioned, and additionally to not requiring oxidizing agents; however, its energy costs for wave creation are high [43]. That is why, this treatment is rarely used for antibiotic removal. It was implemented from 2001 and its use expanded until 2018 with a decrease in publications. However, 3 of the existing publications were selected because of their relevance to the topic to be researched. Their results are found in Table 4 and show a removal above 90% with the use of the method. It is important to mention that it is not consistent to generalize these results, since the number of studies that provide information on the use of the method, are limited.

Electrochemical

The electrochemical consists of the implementation of electrodes and electrolytes that allow the execution of the electrochemical process, where oxyradicals are generated and capable of oxidizing the pollutants, producing CO₂ and H₂O [46]. This method has been widely documented since 1978, with exponential growth in the last 5 years, leaving a total of 266 studies. From the latest research, five studies were selected (see Table 5). As per the results, the most widely used method with a removal efficiency greater than 90% is obtained by anodic oxidation in an electrochemical cell. This method allows the degradation of antibiotics directly and indirectly. However, a common denominator of the research is that the greatest degradation was obtained indirectly. This was thanks to the formation of oxidative agents during the treatment, such as electro-generated active chlorine, which decreases during the time of action, allowing the treatment of a higher flow rate in less time. Additionally, in the presence of chloride ions and basic pH the best removal efficiencies are obtained.

Within the applications of electrochemistry, there is electrolysis, a process that has been implemented in the treatment of wastewater which, through it, the decomposition of a substance is affected thanks to the chemical reactions induced by electricity. During electrolysis, a source in charge of supplying energy is used, an electrolyte to conduct it, an anode and finally a cathode [47]. In this process, the cations are directed towards the cathode and get electrons from it, and the anions are directed towards the anode where they lose electrons; electrolysis is a redox reaction [48].

Punctually of this process, 89 studies using this technology were recorded since 2009, from which 4 are examined and the information on the results is recorded in Table 5. These results show high removal efficiencies, 90% for chlortetracycline and 99.9% for tetracycline. However, any study presents result against the removal of ARB and ARG.

UV irradiation

Ultraviolet radiation has been used in recent years in the removal of pollutants thanks to its great effectiveness. During this process, the frequency of UV light in microorganisms, generates photochemical damage to their nucleic acids, which leads to their inactivation [58]. However, the removal of antibiotics by this method is relevant taking into account that they are photo active, which indicates that they are willing to absorb light bycausing transformations in their structure [29]. To date, about 289 researches related to this method have been registered. Table 6 shows the results obtained during six researches carried out in three countries in 2015, 2016 and 2019. In these studies, there is diversity in the treated contaminants, with nine resistance genes, three resistant bacteria and ten antibiotics. Their results show greater efficiency when it was complemented with other methods such as oxidation with peroximonosulfate (PSM) and chlorination. However, it does not work in the same and generalized way for all types of antibiotics asARB and ARG require the previous identification of the contaminants to be treated.

Most researches that implemented this technology express the removal efficiency on a logarithmic scale, where 0.41 log is equivalent to an removal greater than 85% and 5.3 log is equivalent to 99.99%; in other words, except for the case of the study carried out in Spain, all removal exceeded 90%.

Gamma irradiation

In this technology, radicals, reactive electrons, ions and neutral molecules are generated by exposing water to high-energy electromagnetic radiation; in this way, they modify the pollutant molecules and finally affect their removal [63]. This radiation has been implemented to a lesser extent compared to UV radiation, as it has a total of 59 related documents. The rates of removal of gamma radiation for certain antibiotics, and antibiotic resistance bacteria are high (see Table 7). However, not all are degraded with the same radiation dose, due to their properties and conditions. Additionally, a common factor in obtaining good results in the analyzed studies is that the solution is in an acidic condition, since it allows greater generation of H+ radicals and increases their degradation.

Source: Own elaboration

Membrane bioreactor

Membrane bioreactors are widely used in the secondary treatment of WWTPs; these are composed of a suspended reactor, with membrane separation (micro-filtration or ultra-filtration) to perform biological treatment and solids removal [68]. In the bioreactor, the wastewater that leaves the biological reactor, passes through the membranes where compounds larger than its pore are retained thanks to the negative pressure induced by a pump; this makes possible the separation between water and biomass, where the latter remains in the bioreactor [69]. This technology has been evaluated inthe removal of antibiotics, ARB and ARG, and the results of seven researches have been extracted (see Table 8), where the efficacy in the removal of antibiotics is evidenced by means of membrane bioreactors with an added value, whether microorganisms, hollow fiber or combination of aerobic and anaerobic processes are used. Additionally, with this technology more studies are presented with a focus on ARG and ARB.

Absorption with activated carbon

During this process, there is a solid medium (activated carbon) on which the soluble substance is arranged. This way activated carbon manages to absorb antibiotics and does not generate toxic products [76]. This is possible thanks to the calcination and physical or chemical activation of the carbon, where its porosity varies and the extraction of pollutants by adsorption, becomes effective, as it attaches to other molecules [77]. Adsorption with activated carbon for the removal of antibiotics began approximately in 2007 according to the revised documents. Table 9 shows the results obtained in five researches carried out with this method in four countries, which show the possibility of using organic waste for the preparation of activated carbon in furnaces, which gives added value and can reduce costs of raw material, still achieving removal results greater than 95%. However, its efficiency is reduced in the presence of organic matter in the environment, so it is necessary to implement it after secondary treatment within a WWTP.

In the studies, it was found that with certain doses of activated carbon, the removal of the compounds reached a constant point, which means that the amount of activated carbon is not directly proportional to the removal of the antibiotic. However, it is necessary to provide the surface required for adsorption according to the characteristics of the medium.

Results

Among the documents reviewed, 47 researches were used and their findings were presented regarding the removal efficiency of antibiotics, ARB and ARG. The researches were grouped by continents based on the country where they were developed, resulting in three continents namely; Asia, America and Europe. Asia is the continent where the greatest number of researches were done. This result is due to China's participation is 36% of the total. The interest of this country in testing and developing new technologies that allow the removal of antibiotics, ARB and ARG, is because as a major producer and one of the largest consumers of antibiotics, they are asked to controlling their consumption and reducing their amounts in wastewater; on the contrary, by 2050 bacterial resistance could cause the death of about 1 million people in that country [6], [82]. On the other hand, America has a 26% participation in publications on the subject, where Colombia stands out with 13% of the total research, evidencing the growing concern regarding the problem, due to its impacts on the environment and the population that increases with its low rate of wastewater treatment. Finally, the continent with the lowest participation is Europe with 19%, where Germany and Spain have the same contribution equivalent to 6% of the total studies.

The research shows an inclination towards wastewater, facing the problem that exists in it considering that they were the object of study of 51% of them. This figure was followed by the solutions previously prepared with the contaminants, which correspond to 37% of the researches. The remaining percentage belongs to drinking water, groundwater and seawater.

Among the most evaluated antibiotics for their removal are sulfamethoxazole, trimethoprim, ciprofloxacin and norfloxacin, because these are part of the most prescribed antibiotics [7], and therefore the ones with the greatest attention for removal from wastewater. However, despite being amoxicillin (belonging to the penicillin group), the most consumed antibiotic according to studies conducted in Colombia and in 25 countries in Europe [7], [83]; this research was not representative, considering that it was the object of study of 4 researches from the 47 analyzed.

Additionally, it was determined that the most studied bacterium was Escherichia coli with a total of five researches. The importance of this bacterium is that it is resistant to various antibiotics as confirmed by the study carried out in 2003 by Reinthaler et. al [84], where its resistance was demonstrated in 16 antibiotics out of 24 antibiotics tested. Within these, different resistance rates were found to ampicillin, piperacillin, caphelotine, trimethoprim, sulfamethoxazole and tetracycline, among other antibiotics [84]. However, given the results of this study, it is important to mention that E. coli is still susceptible to various antibiotics [84], [85]. Similarly, the sul1 resistance gene is distinguished within the researches, because it is a sulfamethoxazole-resistant gene [86], which is why it is part of the Escherichia coli genes, increasing resistance to this antibiotic.

In the technologies studied, it is possible to identify variations in their implementation that increase or decrease their removal efficiency. This is the case of discontinued systems and the WEDECO system for ozonation, which improve the performance of the method. Similarly, the photo-fenton treatments, nano electrolysis, photocatalytic treatment with TiO₂ and UV, high frequency ultrasound, anodic oxidation with Ti / IrO₂ as an anode, UVC/PMS radiation, gamma radiation with approximately 2 kGy, bioreactor of hollow fiber membrane, and adsorption with activated carbon made from organic elements. The results of these treatments were retrieved to make comparisons and are presented in Figure 1, where there is a graph based on the technology that shows the removal of each contaminant. This shows that the treatment with fenton was the one with the greatest removal of antibiotics, where 85% of these were completely removed by showing greater performance compared to the electro-chemistry that completely eliminated 71% of the antibiotics treated.

Previous studies confirm the good performance of fenton based reactions against other advanced oxidation processes because it does not produce toxic effluents and achieves high removal efficiencies even more in the presence of light, as is the case with photo-fenton [87], [88]. The latter has also been tested in the presence of oxalic acid and ultrasound, obtaining removal efficiencies of 100%, for metronidazole and clindamycin; whilst for antibiotics such as trimethoprim, ciprofloxacin, norfloxacin, among others, its removal efficiency was less than 70% [89]. The fenton process has been evaluated for the removal of other contaminants, in which it also stands out against the others, since it allows their mineralization and does not generate total organic carbon, once the reaction ends [90]. However, they also expose a series of difficulties when being implemented, due to the rigorous pH range that it handles, iron oxide generation that hinders the process and the instability of the mixture of the agents used [89]. The difficulties presented during the treatment of wastewater can be overcome by choosing the appropriate catalyst, in addition to the application of heterogeneous photo-fenton where the catalyst exhibits greater stability [91].

The results of previous reviews on the efficiency of electro-chemistry highlights its success in water remediation and its current growing research as it additionally eliminates persistent organic pollutants and presents advantages such as low costs, easy implementation and use [92]. Advantages which are due to the saving of chemical products, thanks to the generation of oxidizing agents in situ and the operation of the technology in environmental conditions [93]. However, this technology is still at an intermediate level of technological preparation, which makes it difficult to apply at the industrial level. It is necessary to study components such as the anode and cathode, in order to make an adequate selection of it which allows optimal operating conditions, as well as the development of a mechanical design, suitable for the electrochemical cell [94].

In the case of resistance genes, photocatalysis is the treatment that has the highest removal efficiency compared to the genes studied (mecA and ampC), followed by UV radiation that shows the greatest removal of the sul1 and intl1 genes. Additionally, it was found that the photocatalysis performance is again superior to ozonation in the removal of resistant bacteria, together with gamma radiation that presents a complete removal of Staphylococcus.

Photocatalysis proves to be a convenient technology for the removal of bacteria and resistance genes at the same time. This is a result consistent with previous research that shows this method as promising, by achieving the degradation of a high range of pollutants, with benefits such as stability of the catalyst, the operation under lower limitations regarding the pH of the solution and the possible decrease in operating costs due to the use of sunlight [95], [96]. During photocatalysis it is possible to implement different catalysts such as Al₂O₃, ZnO, Fe₂O₃ and TiO₂ [96]. However, the efficiency of TiO₂ photocatalysis for wastewater disinfection, is highlighted, as it reaches lower toxicity and cost, as well as complementing it with other methods such as UV radiation, in order to accelerate reactions [95], [97], both variables coincide with the selection of the best application of photocatalysis in this review.

As for gamma radiation, other studies also emphasize its potential, due to by means of ionizing radiation, it is possible to attack antibiotic molecules directly and also damage microbial DNA obtaining optimal results [98]. Despite this, this technology is rarely used for the treatment of wastewater because of its high investment cost and the inputs required for its operation [99], a disadvantage that can be overcome by combining gamma radiation with biological treatments in WWTP [100].

Regarding the operating costs of the most important technologies in the elimination process, although there are few studies detailing this variable, the research carried out in 2009 by Pablo [101] showed that the treatment of wastewater by fenton processes represents a lower cost, compared with other POAs such as ozonation and electrochemistry; the cost is around 8 USD (5.75 €) per m³, versus 81 and 15 USD per m³ (58.24 € and 10.785 € per m³ approximately to date). The results were obtained in the elimination of chlorophenol [101]. This research can be compared with one carried out in 2015, where estimated operating costs of photocatalysis and photo-fenton were determined at 8.69 and 5.2 € per m³ respectively, during the treatment of wastewater from the pesticide industry [102].

The costs of each technology will vary depending on the pollutant load and the target pollutants, as well as the modifications made in each implementation. A clear example of the last variable, was evidenced in a research where the costs of the conventional fenton process were compared, with photo-fenton in the elimination of adsorbable organic halogens; reaching costs of € 70.0 and € 46.5 per m³ respectively [103].

Conclusions

In recent decades, research has been done to evaluate the technologies in the removal of antibiotics, ARB and ARG from wastewater, as they cause alterations in the aquatic environment and affect public health. In these area, there is the collaboration of several countries; however, the most representative is China, since its interest is driven by being the largest producer and one of the largest consumers of antibiotics in the world.

During the development of the article, 9 technologies were identified in the removal of the target pollutants, such as the advanced oxidation process (AOP) with ozone, fenton, photocatalysis, ultrasound, electrolysis, electrochemistry, UV radiation and gamma radiation, as well as membrane bioreactors and activated carbon adsorption. Within these technologies, the ones that are most effective for the removal of antibiotics according to the analysis of the information are the fenton and electrochemical processes, achieving the complete removal of some of them. On the other hand, for the removal of ARB and ARG, the photocatalysis and gamma radiation processes were more efficient, respectively. In each of the mentioned technologies, they presented modifications that increased their efficiency. In that sense, the importance of innovating on conventional processes is highlighted, in order to achieve better results and meet the need to eliminate these pollutants in wastewater, given the problems that cause the environment and the population.

During the choice of technology to be implemented within a WWTP, for the removal of these contaminants, it is necessary to also characterize the type of water to be treated, in order to determine its presence in detail and select the one that best suits the conditions, including the other physicochemical parameters to remove. However, a substantial variables exist in the cost of each treatment with the respective variations or combinations that increase its efficiency; therefore, it is recommended to continue the research through a financial analysis of the technologies.

References

Notes

* Review paper

Author notes

^a Corresponding author. E-mail: mariazapataz@usantotomas.edu.co

Additional information

How to cite this article:: M. C. Zapata-Zuñiga, M. Á. Parra-Pérez, J. A. Álvarez-Berrio, and N. I. Molina-Gómez, “Technologies in wastewater treatment plants for the removal of antibiotics, resistant bacteria and antibiotic resistance genes: A review of the current literature,” Ing. Univ., vol. 26, 2022 [Online]. https://doi.org/10.11144/Javeriana.iued26.twtp

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