Colonization of methicillin-resistant Staphylococcus aureus among healthcare students: an integrative review

ABSTRACT BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is a worldwide concern given its presence even in non-hospitalized healthy individuals, such as university students. OBJECTIVE: To identify in the literature the prevalence of colonization by MRSA among healthcare students. DESIGN AND SETTING: Integrative review of the literature conducted in Universidade Federal do Piauí. METHOD: A search for primary studies was performed in the following databases: Medical Literature Analysis and Retrieval System on-line; Cumulative Index to Nursing and Allied Health Literature; Web of Science; Scopus; and LILACS. RESULTS: This review included 27 studies that demonstrated MRSA infection prevalence ranging from 0.0 to 15.3% among students. CONCLUSION: The prevalence of colonization of MRSA among healthcare students is high, and the nasal cavity was cited as an important reservoir location for these microorganisms.


INTRODUCTION
Staphylococcus aureus is considered to be a persistent member of the human endogenous microbiota and has historically been associated with important and serious cases of infection. It has the ability to rapidly develop resistance to antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) is considered to be a paradigm for bacterial infections, since it is associated with high rates of morbidity and mortality. [1][2][3] In assisting carriers of bacterial infections or colonized or infected patients, or in handling contaminated objects, healthcare workers' hands can become contaminated. These workers may subsequently transmit the microorganism to other patients. However, this situation is not exclusive to the hospital environment. Clinically manifested diseases in the community or in professionals and/or patients may lead to situations in which some individuals are asymptomatic carriers, also called colonized individuals or simply carriers, when the disease is present in the host organism without causing apparent manifestations. 1,4 In the United States and Taiwan, the prevalence of strains acquired in the community is 52%, thus exceeding the proportion of strains acquired in hospital environments. 5 There have also been reports of cases of MRSA acquired in the community. 6,7 Healthcare students play an important role in the epidemiology and pathogenesis of Staphylococcus aureus infection and can act as a source of dissemination both in the community and in hospital environments, and for carrying bacteria from one of these environments to another. 1 In Brazil, this topic has been little addressed, but it is known that the presence of MRSA among students has been gradually spreading. 1 Hence, it has become relevant to summarize the knowledge of MRSA that has resulted from research on this subject.

Research design
This study was an integrative review of the literature, incorporating a method of searching for secondary data. 8 To preserve methodological rigor, the following steps were taken to conduct this review: formulation of the research question; idealization of sampling plan and data collection strategies; extraction of relevant data from studies included in the review; and, finally, analysis and interpretation of the data. 8 The research question was elaborated in accordance with the PVO strategy (P -population; V -variable of interest; O -outcome). Thus, in line with the objective of the study, the following structure was used: P -healthcare students; V -methicillin-resistant Staphylococcus; O -prevalence. 9 Therefore, the following question was asked: "What evidence is available in the literature regarding the prevalence of methicillin-resistant Staphylococcus aureus colonization among healthcare students?"

Data collection period
Searching for and selection of studies took place between the months of November 2019 and January 2020 and were carried out by two independent reviewers. Any divergences were resolved by a third reviewer.

Selection criteria
After the search stage, original articles were selected, based on reviewing their titles and abstracts, in accordance with the following inclusion criteria: original articles covering the population of undergraduate students in the field of healthcare who experienced clinical activities that brought them into direct contact with patients.
The full text of each article was then read, with a view to choosing studies that answered the research question. Through this process, articles involving high school or technical students, those that did not comply with selection criteria mentioned above, those that did not answer the research question and those that were duplicates were excluded, as also were opinion articles, theoretical reflections, dissertations and book chapters.

Data collection
The following databases were selected: Medical Literature  Table 1 shows the descriptors used in this study and summarizes how the search was carried out. "Students" OR "Students, Health Occupations" OR "Students, Nursing" OR "Students, Pharmacy" OR "Students, Medical" OR Students, Dental" OR "Health Occupations Students" OR "Health Occupations Student" OR "Student, Nursing" OR "Nursing Student" OR "Nursing Students" OR "Pharmacy Students" OR "Student, Pharmacy" OR "Pharmacy Student" OR "Medical Students" OR "Student, Medical" OR "Medical Student" OR "Dental Students" OR "Student, Dental" OR "Dental Student" "Staphylococcus aureus" "Methicillin Resistance" OR "Resistance, Methicillin" OR "Methicillin-

Data processing and analysis
The studies thus found were exported to the Endnote reference manager software, version 20 (Clarivate Analytics, Philadelphia, United States), in order to identify duplicates and gather together all publications. In addition, the reference lists of these articles were consulted in order to find any additional studies. The selection of studies followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 9 (Figure 1). For data analysis and extraction, a data collection instrument that had been validated by Ursi was chosen for this study and was adapted for use in it. 10 Furthermore, the protocol for this review was previously assessed by experts in the method used. After fully evaluating the texts, a descriptive analysis on the results found was carried out, in which a synthesis of all the studies included in the review was presented, along with comparisons between them.

RESULTS
The final sample for this review comprised 30 primary articles, which were characterized taking into account the authors, year of publication, country, objective and main results ( The populations addressed by the researchers of these 30 studies were nursing students, medical students, health science students and dental students. 3,5,7,[12][13][14][15][16][17][18]20,21,[23][24][25]27,[29][30][33][34][35][36][37] Two studies involved students from more than one undergraduate course. 11,22,28 To detect colonizing microorganisms, samples were collected using the technique of swab smears from nasal specimens, in all of these studies except for four studies, in which specimens were collected from more than one anatomical site. 3,5,7,15-17,18-27-30,33-37 Regarding the prevalence of MRSA, the student population in some studies was divided into groups before exposure to healthcare and after such exposure. 14,19,21,23,26 The percentages found are shown in Table 3. To investigate the prevalence, antimicrobial susceptibility and molecular factors characteristic of CA (community acquired) MRSA among two groups of college students (medical and non-medical).

A25
Budri et al. 33 2018 Ireland To investigate co-located nasal Staphylococcus aureus and coagulase-negative staphylococci (CoNS), recovered from healthy medical students in a preclinical year and the transportation of genes and common elements to both species that may contribute to the evolution of S. aureus and MRSA.

A26
Al-Tamimi et al. 34 2018 Jordan To investigate the prevalence, standard antimicrobial susceptibility, antibiotic resistance genes and risk factors of medical students with MRSA.

A27
Suhaili et al. 35 2018 Malaysia To evaluate the antimicrobial susceptibility profile of S. aureus strains isolated from university students and to determine the prevalence of resistance to constitutive and inducible clindamycin, in which the latter would be capable of causing therapeutic failure due to false in vitro susceptibility to clindamycin.

A28
Onanuga et al. 36 2019 Nigeria To determine the antibiogram and the virulent characteristics of nasal S. aureus, accessing its profile of resistance to antibiotics and potential pathogens in healthy students at the University of the Niger Delta, Bayelsa State, Nigeria.

A29
Szymanek-Majchrzak et al. 37 1,40 This was observed in the present study, thus indicating that MRSA infection was present in students who were not exposed to hospital environments. This may indicate the presence of community-acquired MRSA strains. 1 It needs to be borne in mind that in the studies discussed here, students who had been hospitalized within the last few months had been excluded, considering that hospitalization could be a confounding factor for occurrences of MRSA. Identification of high frequencies of MRSA in students before they were exposed to experiences of clinical care is a matter for concern. It indicates that there is a need for effective infection prevention and control policies, in relation to hygiene and surveillance. 5 Clinical practice among students in the field of healthcare is part of the teaching-learning process. In relation to this process, there is exposure to occupational risks, especially through recognition of the variability of care provided to patients. 1,5  The throat and palms are also important reservoirs for MRSA. 19,21,22,26 It is known that students in the field of healthcare, as they progress through the curriculum with increasing complexity of care practices, whether in hospitals or other healthcare delivery environments, become carriers of microbes. In this, acquisition of Staphylococcus aureus is considered to be a major concern, especially with regard to MRSA. 1 Thus, MRSA rates in students may increase according to their clinical exposure, as well as from isolated occurrences. In another study, there was greater potential for virulence in samples from groups working in clinics. 5 This aspect of infection could not be analyzed in the present study, since the studies included in this review were cross-sectional, which did not allow the study sample to be monitored.
The prevalences found need to be analyzed with caution, considering that occurrences of infections caused by MRSA may differ according to the scenarios within which they occur. This may be due to measures that are taken to control infection and may be dependent on effective implementation. 5 Likewise, the MRSA rate also varies in different locations. 27,41 This study presented some limitations due to the choice of databases and keywords. Use of the CINAHL database may have restricted the search, as it is a specific database for the field of nurs- ing. In addition, the choice of databases and keywords may have camouflaged studies on the same topic that were not indexed in the same database. Hence, it can be suggested that similar investigations should be conducted, with cross-referencing of other databases, in order to investigate Brazilian scientific production on colonization by Staphylococcus aureus among healthcare students.

The prevalence of colonization by methicillin-resistant
Staphylococcus aureus among healthcare students is high, and the nasal cavity was cited in this study as an important reservoir for these microorganisms.
Efforts need to be made to implement standards and routines that are designed to limit the spread of MRSA strains among students, given that once MRSA has become established within a community, its eradication and control is difficult. Furthermore, in view of the high morbidity and mortality and exponential growth of series of microbial resistance, implementation of control strategies is prudent.
Therefore, education on infection control measures in undergraduate healthcare courses is of great importance, as also is implementation of adequate and effective infection control programs to reduce the prevalence of MRSA.