Prevalence of Staphylococcus aureus and MRSA among Medical students: a literature review Prevalência de Staphylococcus aureus e MRSA entre estudantes de Medicina: uma revisão de literatura Prevalencia de Staphylococcus aureus y MRSA en estudiantes de Medicina: una revision de la literatura

Objective: The aim was to analyze the results of studies about the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus among medical students. Methodology: A literature review was carried out from August to November 2020, being selected 19 articles from the Pubmed and “Biblioteca Virtual de Saúde” databases, using the descriptors “Methicillin-Resistant Staphylococcus aureus” and “Students, Medical”. Studies from the last 10 years that target medical students and samples collected by nasal swab were included. Results: Several studies have Research, Society and Development, v. 10, n. 11, e347101119536, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i11.19536 2 confirmed the hypothesis that, as students advanced in the academic years and, consequently, raised their exposure to hospital environments, colonization by methicillin-sensitive and resistant Staphylococcus aureus increased. However, some studies were divergent, not finding significant values for this association. The prevalences found also varied according to the place and country surveyed. Conclusion: In general, the greater the exposure to hospital environments, the higher the rate of colonization of students by methicillin-resistant Staphylococcus aureus and Staphylococcus aureus.


Introduction
Nowadays, Staphylococcus aureus (S. aureus) is the leading cause of community and nosocomial infections (Okamo et al., 2016). This bacterium is an important colonizer of the humans' skin and mucosa, mainly anterior nasal cavity, but also perineum, pharynx, gastrointestinal tract, vagina and armpits (López-Aguilera et al., 2013). From the microbiota, in susceptible patients, the bacteria can infect skin, soft tissues, lungs, bones, joints and blood circulation (Chamberlain & Singh, 2011).
Thus, that is a significant cause of mortality and morbidity in immunosuppressed patients, patients on hemodialysis, with prolonged hospitalizations and advanced age, besides smoking, alcoholism and chronic respiratory diseases (Ma et al., 2011;Rampal et al., 2020). In 2017, the microorganism was included in the World Health Organization's (WHO) List of Priority Pathogens, ratifying its relevance on the world stage (Szymanek-Majchrzak et al., 2019).
In the 1960s, a strain of methicillin-resistant Staphylococcus aureus (MRSA) was first isolated (Jayaweera et al., 2020). It is now known that this variant is due to the mec(A) and SCCmec genes, which encode altered penicillin-binding proteins (PBP), conferring resistance to beta-lactams and methicillin (Alzoubi et al., 2020). With the emergence of this resistant strain, there has been an increase in the therapeutic complexity of hospital-acquired infections, as well as Research, Society andDevelopment, v. 10, n. 11, e347101119536, 2021 (CC BY 4.0) | ISSN 2525-3409 | DOI: http://dx.doi.org/10.33448/rsd-v10i11.19536 3 hospitalization time and treatment costs (Alzoubi et al., 2020;Rodríguez-Avial et al., 2013). Studies proves that individuals exposed to a hospital environment for long periods have a greater chance of carrying S. aureus or MRSA in the nasal microbiota and, consequently, healthcare workers can be a source of transmission of nosocomial infections (Alzoubi et al., 2020;Okamo et al., 2016). Most of the population is an intermediate carrier of S. aureus, while the rest is divided between those who are always colonized and those who never acquire the microorganism (Ansari et al., 2016). In 2011, MRSA infections were estimated to account for about 50-63% of all nosocomial infections in the United States (Chamberlain & Singh, 2011). The current percentage of MRSA among S. aureus has been increasing, however, worldwide, it varies by region, corresponding to rates of 20 to 80% of all S. aureus (Alzoubi et al., 2020). In South America, North America, Malta and Asia, MRSA prevalence rates were greater than 50%. In South America, Brazil was one of the countries that showed prevalence greater than 50% (Santos, 2018). However, despite being a microorganism of global relevance, in Brazil, there has been a scarcity of published data on the topic, which hinders the delineation of its real epidemiology in the country (Evangelista & Oliveira, 2015). The variation in prevalence among countries can be explained by geographic location, the extent of environmental exposure to risk factors, as well as different policies for infection control and prevention (Okamo et al., 2016).
Several studies have investigated the prevalence of MSSA (methicillin-susceptible Staphylococcus aureus) and MRSA among medical students, in order to compare whether those on clinical postings, with greater contact in hospital institutions, had a higher prevalence of these microorganisms than students in the basic cycle, or only to analyze the profile of the students as carriers of the pathogens mentioned above. This review aims to make an analysis and interpretation of these studies, presenting a synthesis of the found data, besides discussing the reasons that led to the results presented by each one of them. Considering the small number of data found in the literature, this study aims to perform a literature review on the prevalence of MSSA and MRSA among medical students in different locations worldwide. In order to allow an epidemiological analysis and to direct prevention and treatment policies for these infections, as well as to encourage the inclusion of medical students in these actions.

Methodology
In this article, a literature review was conducted from August to November of 2020, using articles from the last 10 years for its writing. We included articles in Portuguese, English and Spanish that had medical students as target population and samples collected by nasal swab.
Initially, articles from the Scielo, Pubmed and "Biblioteca Virtual de Saúde" (BVS) databases were searched, applying the descriptors "Methicillin-Resistant Staphylococcus aureus" and "Students, Medical". From this search, four, 86 and 65 results were found, respectively, from which, one, 19 and 8 articles were selected (Table 1). From this initial selection, articles that involved a sample with graduate professionals, students from other courses (Chinese medicine, nursing, pharmacy and dentistry, medical labor sciences), non-nasal collections, or those involving the general population were excluded. The only exception was the article by Shadi A. Zakai (2015), which despite containing both resident physicians and medical students in its sample, made it possible to analyze the students in isolation, allowing the exclusion of only the part corresponding to resident physicians without having to eliminate the article as a whole. Thus, the final selection did not include articles from the Scielo database and included 17 articles from Pubmed and two from BVS, totaling 19 articles for the study.
After the criterion selection of articles, the studies were read and analyzed for data collection, evaluating the type of study, location, sample details, culture media and identification tests that were used, and the described resistance standard. Of these selected studies, most have a cross-sectional methodology and are concentrated in Asia, and none of them were conducted in Brazil.
Furthermore, in the selected papers, the prevalence of MRSA and S. aureus among medical students was emphasized.
Therefore, the main objective of the present paper is to analyze the relation between the presence of MRSA and S. aureus and the time of clinical exposure, comparing the findings in preclinical and clinical students, as well as observing other risk factors that were presented in the studies.

Results and Discussion
The articles analyzed in this study varied both in location, being distributed in several countries, and in the culture media used for growth of the microorganism and analysis of the resistance profile. In addition, the samples collected were also varied. In general, we can divide medical students into those who were in the preclinical stage at the university at the time of sample collection and those who were already in clinical stage, the latter being in greater contact with the hospital and, therefore, presenting more risk of being carriers of S. aureus and MRSA, since one of the most common routes of infection is the health professional-patient route (Chamberlain & Singh, 2011).
Regarding the culture media that were used, there was a prevalence in the use of sheep blood agar and salt mannitol agar for the cultivation of S. aureus, as well as Mueller Hinton agar to perform the antibiogram. In addition to these agars, some studies used methods diverging from each other, as in the study by Szymanek-Majchrzak et al. (2019) which used Chapman agar; the article by Ma et al. (2011), which used Columbia agar; and the work by Ansari et al. (2016), which applied DNAse agar. The studies by Jayaweera, Pilapitiya and Kumbukgolla (2020); Treesirichod, Hantagool and Prommalikit (2014); and Gualdoni et al. (2012), used MacConkey agar, with the latter two also making use of chocolate agar. The study by Rodríguez-Avial et al. (2013), on the other hand, used chromID SAID agar and chromID MRSA agar with methicillin for the growth of S. aureus and for the antibiogram, the diffusion method on MH2 agar was used.
Some articles also used nutrient broth for bacterial growth, such as brain heart infusion agar with the presence of NaCl at 7,5%, tryptone soy broth enriched agar and mannitol salt agar, quoted sequentially as Jayaweera et al.  (2015), and Budri et al. (2018). The methodology presented in each article is resumed in Table 2. The articles' samples were classified in preclinical or clinical according to the definition presented in each research, since this data can vary because of the curriculum of each university. In studies where this definition was not available, clinical students were considered the ones from the third year and forward. The results of each study were detailed in Table 3, in which initially can be observed a large variability showed in the results, considering that good part can be explained by the prevalence difference of the microorganism in each country, also by the different pathogen control actions and due the irregular exposures to environmental factors in each institution (Okamo et al., 2016). Hospital exposure presents itself as an important risk factor for the colonization by S. aureus and MRSA, an example of that is evident in the study conducted by Rodríguez-Avial et al. (2013), whereupon students from the same class were monitored, first when they were in the third year and again when they reached the sixth year, after having been exposed to activities in ambulatories and hospitals for a longer time. In the first analysis, 14 of 52 students were colonized with S. aureus (26,92%) and none of them had presented MRSA. Therefore, in the collection after three years, 81 students participated and of these, 37 (46,25%) had S. aureus and 1 (1,25%) were colonized with MRSA.
In the Efa et al. (2019) studies, samples taken from students of those same undergraduate years were analyzed, all from clinical cycle, and the same increasing pattern was observed in the prevalence of individuals with MRSA (fourth year: 3.6%; fifth year: 7.2%; and sixth year: 20%), as well as S. aureus in general. In the studies realized in Thailand conducted by Treesirichod et al. (2013Treesirichod et al. ( , 2014, third year students were analyzed in three different moments, the first before they started the wards rotations, the other after the first rotation and the last collection at the end of all rotations. Among the 128 students, although there were none colonized by MRSA, it was possible to observe a gradual increase in the prevalence of MSSA, which went from 29,7% in the first collection to 39,4% in the third. Likewise, other studies have also shown a significantly association between MRSA transport and time of exposure to the hospital. In Jayaweera et al. (2020), three batches of medical students, from first, third and fifth year, were screened for MRSA colonization. Before having been exposed to healthcare settings, only 6.4% of 1 st year students were MRSA carriers.
After six months of starting their clinical training, these same students were re-screened, and the MRSA colonization was increased up to 28.1%. The 5 th year students, who were exposed to healthcare settings for two years and six months duration, showed an even greater increase with 49.6% MRSA colonization.
The Graphic 1 illustrates how most of articles that studied both preclinical and clinical students found an increase in the prevalence of S. aureus as the hospital exposure of students rises over the course.
Graph 1 -Comparison between the prevalence of Staphylococcus aureus in the studies that investigated samples in clinical and preclinical students.
Note: to make the graphs, the percentages were calculated using the number of samples informed in the studies in cases where the values presented were only absolute. Source: Authors.
However, some cross-sectional studies highlighted that, in their institutions, there was no significance between hospital exposure and the presence of MRSA. According to Chen et al. (2012), the prevalence of MRSA in preclinicals was 2.4% while clinical was 1.9% after 1 to 2 years of exposure. In the study by Alzoubi et al. (2020), MRSA was found in 1.9% of students in preclinical years and 2.8% among clinical years, but the years of each cycle were not distinguished. Whereas in two studies, no MRSA cases were found (Gualdoni et al., 2012;Syafinaz et al., 2012). The results found in other studies, in addition to those described in Table 3, have been summarized in Graphs 2 and 3.

Conclusion
After a thorough analysis of the selected articles, it was possible to conclude that the increase of hospital exposure time, i.e., the increase of time spent in outpatient clinics and wards by students as they progress through the medical course (preclinical to clinical), increases the possibility of contamination by Staphylococcus aureus and MRSA, since the studies that pointed otherwise were not significant.
This exposure, besides representing risk to the students themselves, also contributes to the transmission of this pathogen to the patients who seek care in hospital environments, which can worsen the prognosis, increase mortality rates and length of hospital stay. Another point to be considered is that the presence of other factors may also be related to the portability of S. aureus, such as chronic sinusitis, smoking, male gender, individuals older than 23 years old, other upper respiratory tract infections and the presence of chronic diseases. In general, the use of antibiotic therapy in the last 3 months had divergences regarding its influence on the carriage of S. aureus.
Therefore, it is clear the need for structuring educational actions, both in hospitals and in medical teaching institutions, aimed at hand washing practices, monitoring of hospital infections and awareness of professionals and students about these issues. Since the data studied in this paper vary according to the time and places studied, it is recommended that new studies on the subject be carried out constantly, in order to evaluate the evolution of the profile of MRSA and S. aureus infections among medical students.