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Fatores associados à infecção por Staphylococcus aureus resistente à meticilina em unidade de terapia intensiva

Factores asociados a la infección por staphylococcus aureus resistente a la meticilina en una unidad de terapia intensiva

ABSTRACT

Objective:

To identify factors associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in adult patients admitted to the Intensive Care Unit (ICU), and to compare them with a control group.

Methods:

Retrospective case-control study carried out in an adult ICU, from January 2015 to June 2017, with 61 patients who developed methicillin-resistant Staphylococcus aureus infection and the same number of control patients.

Results:

Most participants were male 65 (60.6%), with a neurological diagnosis 43 (35.2%) and hypertensive 61 (50.0%). In the comparison of the groups, there was a statistically significant difference in relation to mechanical ventilation (p=0.0107), tracheostomy (p=0.0083), death (p=0.0401), urinary catheter (p=0.0420), length of stay (p<0.0001) and severity (p=0.0003). The main factors associated with methicillin-resistant Staphylococcus aureus infection were: severity (OR= 65.69; CI=3.726-4.808; p=0.0018), use of antimicrobials (OR= 0.047;CI=0.028-0.122;p=0.0024), length of stay (OR=1.19; CI=0.952-1.031; p=0.0285).

Conclusion:

methicillin-resistant Staphylococcus aureus infection is multifactorial and has been associated with length of stay and severity. Use of antimicrobials was a protective factor.

Descriptors:
Staphylococcus Aureus; Intensive Care Unit; Nursing; Infection Control; Microbial Drug Resistance

RESUMEN

Objetivo:

Identificar los factores asociados a la infección por Staphylococcus aureus resistente a la meticilina (SARM) en pacientes adultos internados en una Unidad de Cuidados Intensivos (UCI) y compararlos con un grupo control.

Métodos:

Se trata de un estudio de caso-control, retrospectivo, realizado en una UCI de adultos entre enero de 2015 y junio de 2017, con 61 pacientes que desarrollaron la infección por Staphylococcus aureus resistente a la meticilina y el mismo número de control.

Resultados:

La mayoría de los participantes tenía 65 años (60,6%) y era del sexo masculino; 43 (35,2%) poseían diagnóstico neurológico y 61 (50,0%) padecían de hipertensión. En la comparación de los grupos se observó una diferencia estadísticamente significativa en relación con la ventilación mecánica (p=0,0107), la traqueotomía (p=0,0083), la muerte (p=0,0401), el catéter urinario (p=0,0420), los días de hospitalización (p<0,0001) y la gravedad de los pacientes (p=0,0003). Los principales factores asociados con la infección por Staphylococcus aureus resistente a la meticilina fueron: gravedad (OR= 65,69; CI=3,726-4,808; p=0,0018), antimicrobiano (OR= 0,047; CI=0,028-0,122; p=0,0024), días de internación (OR=1,19; CI=0,952-1,031; p=0,0285).

Conclusión:

La infección por Staphylococcus aureus resistente a la meticilina es multifactorial y está asociada al tiempo de internación y a la gravedad de los pacientes. El antimicrobiano fue el factor protector.

Descriptores:
Staphylococcus Aureus; Unidad de Cuidados Intensivos; Enfermería; Control de Infecciones; Farmacorresistencia

RESUMO

Objetivo:

Identificar os fatores associados à infecção por Staphylococcus aureus resistente à meticilina (MRSA) em pacientes adultos internados em Unidade de Terapia Intensiva (UTI), e compará-los com um grupo controle.

Métodos:

Estudo caso-controle, retrospectivo, realizado em UTI adulto, no período de janeiro/2015 a junho/2017, com 61 pacientes que desenvolveram infecção por Staphylococcus aureus resistente à meticilina e o mesmo número de controle.

Resultados:

A maioria dos participantes era do sexo masculino (60,6%), com diagnóstico neurológico (35,2%) e hipertensos (50,0%). Na comparação dos grupos, houve diferença estatisticamente significante em relação à ventilação mecânica (p=0,0107), traqueostomia (p=0,0083), óbito (p=0,0401), cateter urinário (p=0,0420), dias de internação (p<0,0001) e gravidade dos pacientes (p=0,0003). Os principais fatores associados à infecção por Staphylococcus aureus resistente à meticilina foram gravidade (OR= 65,69; IC=3,726-4,808; p=0,0018), Antimicrobiano (OR= 0,047;IC=0,028-0,122;p=0,0024), dias de internação (OR=1,19; IC=0,952-1,031; p=0,0285).

Conclusão:

A infecção por Staphylococcus aureus resistente à meticilina é multifatorial e se associou ao tempo de internação e à gravidade dos pacientes. Antimicrobiano foi fator protetor.

Descritores:
Staphylococcus Aaureus; Unidade de Terapia Intensiva; Enfermagem; Controle de Infecções; Resistência Microbiana a Medicamentos

INTRODUCTION

Health Care-Associated Infections (HAIs) are not only a biological event, but a historical and social phenomenon that has a direct impact on safety of health care and is one of the main challenges to quality health care(11 Al-Tawfiq JA, Tambyah PA. Health care associated infections (HAI) perspectives. J Infect Public Health. 2014; 7(4):339-44. doi: 10.1016/j.jiph.2014.04.003
https://doi.org/10.1016/j.jiph.2014.04.0...
-22 Allegranzi B, Bagheri Nejad S, Combescure C, Graafmans W, Attar H, Donaldson L, et al. Burden of endemic health-care-associated infection in developing countries: systematic review and meta-analysis. Lancet. 2011; 377(9761):228-41. doi: 10.1016/S0140-6736(10)61458-4
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).

The Center of Diseases Control and Prevention (CDC) estimates that almost 1.7 million HAIs occur annually in patients being treated for other health problems, and that more than 98,000 of these patients (one in 17) die from it(33 Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, et al. Estimating health care-associated infections and deaths in U. S.hospitals, 2002. Public Health Rep. 2007; 122(2):160-16. doi: 10.1177/003335490712200205
https://doi.org/10.1177/0033354907122002...
). In Brazil, data on HAIs are still poorly documented due to the reduced standard of information in several hospitals, which makes it difficult to know the magnitude of the problem in the country(44 Souza ES, Belei RA, Carrilho CMDM, Matsuo T, Yamada-Ogatta SF, Andrade G, et al. Mortalidade e riscos associados a infecção relacionada à assistência à saúde. Texto Contexto Enferm. 2015; 24(1):220-8. doi: 10.1590/0104-0707201500294001
https://doi.org/10.1590/0104-07072015002...
). A study carried out by the Ministry of Health evaluated 99 tertiary hospitals linked to the Unified Health System (SUS) and located in Brazilian capitals and found that the prevalence of HAIs among hospitalized patients was 13%(55 Agência Nacional de Vigilância Sanitária. Epidemiologia para o controle de infecção hospitalar. Caderno A [Internet]. Brasília (DF): ANVISA; 2000[cited 2020 Jan 20]. Available from: http://www.cvs.saude.sp.gov.br/pdf/CIHCadernoA.pdf
http://www.cvs.saude.sp.gov.br/pdf/CIHCa...
).

It is estimated that HAIs in critically ill patients represent 20% of all infections in hospitalized patients(66 Gupta K, Martinello RA, Young M, Strymish J, Cho K, Lawler E. MRSA nasal carriage patterns and the subsequent risk of conversion between patterns, infection, and death. PLoS ONE. 2013;8:e53674. doi: 10.1371/journal.pone.0053674
https://doi.org/10.1371/journal.pone.005...
-77 Ferreira LL, Azevedo LMN, Salvador PTCO, Morais SHM, Paiva RM, Santos VEP. Cuidado de enfermagem nas Infecções Relacionadas à Assistência à Saúde: scoping review. Rev Bras Enferm. 2019; 72(2):476-483. doi: 10.1590/0034-7167-2018-0418
https://doi.org/10.1590/0034-7167-2018-0...
), 15% of primary bloodstream infections(88 Rodrigues AWS, Camargo B, Maciel EP. Research of methicillin-resistant staphylococcus aureus (MRSA) in hospital elevators of the private network of Brasília - DF. Rev Bras Pesqui Ciên Saúde [Internet]; 2019 [cited 2020 Jan 20] 6(11):13-18. Available from: http://revistas.icesp.br/index.php/RBPeCS/article/view/814/647
http://revistas.icesp.br/index.php/RBPeC...
) and correspond to almost half a million cases per year in intensive care units (ICUs)(99 Araújo PL, Mendonça AEO, Medeiros RA, Souza Neto VL, Nobre TTX, Costa IKF. Prevalence of health assistance infection in patients hospitalized in intensive therapy unit. Enferm Global [Internet]; 2018 [cited 2020 Jan 20] 52:304-315. Available from: http://scielo.isciii.es/pdf/eg/v17n52/en_1695-6141-eg-17-52-278.pdf
http://scielo.isciii.es/pdf/eg/v17n52/en...
). Among these infections, contamination by Staphylococcus aureus is among the main causes of morbidity and mortality and is associated with high rates of health care-associated complications, especially in developing countries(1010 Kim JJ, Blevins MW, Brooks DJ, Stehle JR Jr, McLouth CJ, Viviano JP, et al. Successful control of a methicillin-resistant Staphylococcus aureus outbreak in a burn intensive care unit by addition of universal decolonization with intranasal mupirocin to basic infection prevention measures. Am J Infect Control. 2019 Jun; 47(6):661-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30616934
https://www.ncbi.nlm.nih.gov/pubmed/3061...
).

Staphylococcus aureus is a gram-positive bacteria present in the human microbiota, mainly on the skin, which can become pathogenic and lead to an infection when there is a breakdown of the skin barrier or decreased immunity. When this important nosocomial pathogen is resistant to methicillin, it is called MRSA (Methicillin-resistant Staphylococcus Aureus)(1010 Kim JJ, Blevins MW, Brooks DJ, Stehle JR Jr, McLouth CJ, Viviano JP, et al. Successful control of a methicillin-resistant Staphylococcus aureus outbreak in a burn intensive care unit by addition of universal decolonization with intranasal mupirocin to basic infection prevention measures. Am J Infect Control. 2019 Jun; 47(6):661-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30616934
https://www.ncbi.nlm.nih.gov/pubmed/3061...
-1111 Kaur DC, Chate SS. Study of antibiotic resistance pattern in methicillin resistant Staphylococcus aureus with Special Reference to Newer Antibiotic. J Glob Infect Dis. 2015; 7(2):78-84. Available from: https://www.ncbi.nlm.nih.gov/pubmed/26069428
https://www.ncbi.nlm.nih.gov/pubmed/2606...
).

In the hospital environment, one of the most common places for colonization and infection by MRSA is the ICU, where approximately 20% of infected patients are predisposed to death(1212 Majumdar SS, Padiglione AA. Nosocomial infections in the intensive care unit. Anaesth Intens Care Med. 2012; 13(5):204-8. Available from: https://www.anaesthesiajournal.co.uk/article/S1472-0299(12)00035-5/pdf
https://www.anaesthesiajournal.co.uk/art...
). In Latin America, MRSA is the leading cause of nosocomial infection, which shows the importance of identifying risk factors for colonization and infection by this microorganism(1313 Caboclo RM, Cavalcante FS, Iorio NL, Schuenck RP, Olendzki AN, Felix MJ, et al. Methicillin-resistant Staphylococcus aureus in Rio de Janeiro hospitals: dissemination of the USA400/ST1 and USA800/ST5 SCCmec type IV and USA100/ST5 SCCmec type II lineages in a public institution and polyclonal presence in a private one. Am J Infect Control. 2013;41(3):e21-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23261682
https://www.ncbi.nlm.nih.gov/pubmed/2326...
).

Studies have shown that MRSA colonization is still the main risk factor for active infection(1414 Cadena J, Thinwa J, Water EA, Frei CR. Risk factors for the development of active methicillin-resistant Staphyloccus aureus (MRSA) infection in patients colonized with MRSA at hospital admission. Am J Infect Control. 2016; 44(12):1617-21. Available from: https://www.ajicjournal.org/article/S0196-6553(16)30483-7/fulltext
https://www.ajicjournal.org/article/S019...
-1515 Callejo-Torre F, EirosBouza JM, Olaechea Astigarraga P, Coma Del Corral MJ, Palomar Martínez M, Alvarez-Lerma F, et al. Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Infez Med. 2016; 3:201-9. Available from: https://pdfs.semanticscholar.org/3b4f/46688727a215a5bd14c9c1ceaf3a6d42bba7.pdf
https://pdfs.semanticscholar.org/3b4f/46...
). In addition, some predisposing factors are comorbidities such as diabetes, chronic lung disease, prolonged hospitalization, use of invasive equipment or invasive procedures, presence of colonized or infected patients in the same environment, previous hospitalization and exposure to antimicrobials(1414 Cadena J, Thinwa J, Water EA, Frei CR. Risk factors for the development of active methicillin-resistant Staphyloccus aureus (MRSA) infection in patients colonized with MRSA at hospital admission. Am J Infect Control. 2016; 44(12):1617-21. Available from: https://www.ajicjournal.org/article/S0196-6553(16)30483-7/fulltext
https://www.ajicjournal.org/article/S019...
,1616 McKinnell JA, Miller LG, Eells SJ, Cui E, Huang SS. A systematic literature review and meta-nalysis of factors associated with MRSA colonization at time of hospital or ICU admission. Infect Control Hosp Epidemiol. 2013; 34(10):1077-86. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24018925
https://www.ncbi.nlm.nih.gov/pubmed/2401...

17 Catry B, Latour K, Jans B, Vandendriesche S, Preal R, Mertens K, et al. Risk factors for methicillin-resistant Staphylococcus aureus: a multi-laboratory study. PLoS One. 2014;9:e89579. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3935888/
https://www.ncbi.nlm.nih.gov/pmc/article...
-1818 Zarb P, Coignard B, Griskeviciene J, Muller A, Vankerckhoven V, Weist K, et al. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare‐associated infections and antimicrobial use. Euro Surveill. 2012;17(46).pii:20316. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23171822
https://www.ncbi.nlm.nih.gov/pubmed/2317...
).

Longer hospital stays, frequent use of immunosuppressants and/or antimicrobials, nutritional conditions, age, as well as the hands of health professionals are significant factors associated with HAIs(1818 Zarb P, Coignard B, Griskeviciene J, Muller A, Vankerckhoven V, Weist K, et al. The European Centre for Disease Prevention and Control (ECDC) pilot point prevalence survey of healthcare‐associated infections and antimicrobial use. Euro Surveill. 2012;17(46).pii:20316. Available from: https://www.ncbi.nlm.nih.gov/pubmed/23171822
https://www.ncbi.nlm.nih.gov/pubmed/2317...
-1919 Okado JB, Bogni SC, Reinato LAF, Martinez R, Gir E, Camargo ILBDC. Molecular analysis of methicillin-resistant Staphylococcus aureus dissemination among healthcare professionals and/or HIV patients from a tertiary hospital. Rev Soc Bras Med Trop. 2016; 49(1):51-6. doi: 10.1590/0037-8682-0284-2015
https://doi.org/10.1590/0037-8682-0284-2...
). These factors lead to increased hospital morbidity and mortality, prolonged hospitalizations and increased costs and favor the selection and dissemination of multidrug-resistant microorganisms(2020 Kramer TS, Schröder C, Behnke M, Aghdassi SJ, Geffers C, Gastmeier P, et al. Decrease of methicillin resistance in Staphylococcus aureus in nosocomial infections in Germany-a prospective analysis over 10 years. J Infect. 2019; 78(3):215-9. doi: 10.1016/j.jinf.2018.12.005
https://doi.org/10.1016/j.jinf.2018.12.0...
).

It should be noted that overuse and indiscriminate use of antimicrobials results in the development of multidrug-resistant microorganisms and is related to the dissemination and horizontal transmission of HAIs(1010 Kim JJ, Blevins MW, Brooks DJ, Stehle JR Jr, McLouth CJ, Viviano JP, et al. Successful control of a methicillin-resistant Staphylococcus aureus outbreak in a burn intensive care unit by addition of universal decolonization with intranasal mupirocin to basic infection prevention measures. Am J Infect Control. 2019 Jun; 47(6):661-5. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30616934
https://www.ncbi.nlm.nih.gov/pubmed/3061...
,2121 Chamchod F, Palittapongarnpim P. Effects of the proportion of high-risk patients and control strategies on the prevalence of methicillin-resistant Staphylococcus aureus in an intensive care unit. BMC Infect Dis. 2019;19:1026. doi: 10.1186/s12879-019-4632-9
https://doi.org/10.1186/s12879-019-4632-...
). In addition, 8% of patients staying in the ICU for more than two days have acquired at least one HAI(2222 European Centre for Disease Prevention and Control- ECDC. Annual epidemiological report 2016. Health care-associated infections acquired in intensive care units [Internet]. 2016 [cited 2020 Jan 24]. Available from: https://ecdc.europa.eu/sites/portal/ files/ documents/AER-HCAI_ICU_3_0.pdf
https://ecdc.europa.eu/sites/portal/ fil...
).

The relevance of active, systematic and continuous surveillance for hospital infections has the objective of decreasing the number of infections, mainly those caused by MRSA and, consequently, reducing the use of vancomycin for treatment or antibiotic prophylaxis. In addition, it aims to reduce antimicrobial resistance, treatment costs and length of hospital stay(2121 Chamchod F, Palittapongarnpim P. Effects of the proportion of high-risk patients and control strategies on the prevalence of methicillin-resistant Staphylococcus aureus in an intensive care unit. BMC Infect Dis. 2019;19:1026. doi: 10.1186/s12879-019-4632-9
https://doi.org/10.1186/s12879-019-4632-...

22 European Centre for Disease Prevention and Control- ECDC. Annual epidemiological report 2016. Health care-associated infections acquired in intensive care units [Internet]. 2016 [cited 2020 Jan 24]. Available from: https://ecdc.europa.eu/sites/portal/ files/ documents/AER-HCAI_ICU_3_0.pdf
https://ecdc.europa.eu/sites/portal/ fil...
-2323 Oliveira AC, Paula AO, Rocha RF. Custos com antimicrobianos no tratamento de pacientes com infecção. Av Enferm [Internet] 2015[cited 2020 Jan 24];33(3):352-61. Available from: http://www.scielo.org.co/ pdf/aven/v33n3/v33n3a03.pdf
http://www.scielo.org.co/ pdf/aven/v33n3...
).

Nasopharyngeal colonization usually precedes MRSA infections(1515 Callejo-Torre F, EirosBouza JM, Olaechea Astigarraga P, Coma Del Corral MJ, Palomar Martínez M, Alvarez-Lerma F, et al. Risk factors for methicillin-resistant Staphylococcus aureus colonisation or infection in intensive care units and their reliability for predicting MRSA on ICU admission. Infez Med. 2016; 3:201-9. Available from: https://pdfs.semanticscholar.org/3b4f/46688727a215a5bd14c9c1ceaf3a6d42bba7.pdf
https://pdfs.semanticscholar.org/3b4f/46...
). In this sense, early detection of colonized patients minimizes the risk of direct and/or cross-transmission. This has become a growing challenge and therapeutic options have been increasingly restricted due to the resistance of microorganisms to antimicrobials(2121 Chamchod F, Palittapongarnpim P. Effects of the proportion of high-risk patients and control strategies on the prevalence of methicillin-resistant Staphylococcus aureus in an intensive care unit. BMC Infect Dis. 2019;19:1026. doi: 10.1186/s12879-019-4632-9
https://doi.org/10.1186/s12879-019-4632-...
).

The role of the nursing team should be emphasized, as these professionals are the largest providers of specialized health care. The nurse has a fundamental role in the prevention of HAIs in the ICU; with systematized procedures and supported by the best scientific evidence available, these professionals can minimize the risk of unnecessary harm associated with health care. In addition, this study may contribute to the multifaceted management of the prophylactic care that health professionals will have as guidelines to prevent MRSA.

However, despite of the complexity and severity of the issue, the literature review showed that it is not fully addressed in the nursing literature and most of the studies conducted in the ICU do not stratify the sample with its controls to justify the results. Therefore, a study on risk factors contributes to the planning and establishment of strategies for the prevention, control and surveillance of this infection. In this sense, we ask: What are the associated factors for MRSA in adult patients admitted to the ICU in a university hospital?

OBJECTIVE

To identify factors associated with infection caused by methicillin-resistant Staphylococcus aureus in adult patients admitted to the Intensive care Unit and to compare them with a control group.

METHODS

Ethical aspects

The research started after approval by the Research Ethics Committee of the Medical School of Botucatu and in accordance with Resolution 466/12(2424 Conselho Nacional de Saúde (BR). Resolução Nº 466 do Conselho Nacional de Saúde, de 12 de dezembro de 2012 (BR) [Internet]. Aprova as diretrizes e normas regulamentadoras de pesquisas envolvendo seres humanos. Diário Oficial da União. 12 de dez 2012 [cited 2019 Jun 19]. Available from: https://bvsms.saude.gov.br/bvs/saudelegis/cns/2013/res0466_12_12_2012.html
https://bvsms.saude.gov.br/bvs/saudelegi...
).

Study design, setting and period

This is a retrospective, descriptive, case-control study with a quantitative approach. In this study, the qualification strategy for observational studies in epidemiology (STROBE) was followed(2525 Von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. Strengthening the reporting of observational studies in epidemiology (STROBE): Checklist for case-control studies [Internet]. 2007 [cited 2019 Jun 10]. Available from: https://www.strobe-statement.org/fileadmin/Strobe/uploads/checklists/STROBE_checklist_v4_case-control.pdf
https://www.strobe-statement.org/fileadm...
).

The study was carried out in a general adult intensive care unit with 25 beds in a public hospital in the State of São Paulo, in the period between January 2015 and June 2017.

Study sample; inclusion and exclusion criteria

Non-probabilistic convenience sample, consisting of adult patients who developed MRSA infection during ICU stay. Participants were 18 years old or over, of both genders and duly documented in the electronic medical record by the team of the Comission for the Control of Health Care-Associated Infections (CCIRAS) of the institution. Patients who had an infection acquired in the community or had a previously known infection at the time of admission to the ICU or readmissions were excluded.

An infection acquired in the community is one whose incubation or development period was already in course at hospital admission and that cannot be related to a previous hospitalization period, health interventions or procedures performed(2626 Ministério da Saúde (BR). Portaria nº 2616, de 12 de maio de 1998 [Internet]. Diário Oficial da União. 12 de maio 1998[cited 2020 Jan 20]. Available from: http://bvsms.saude.gov.br/bvs/saudelegis/gm/1998/prt2616_12_05_1998.html
http://bvsms.saude.gov.br/bvs/saudelegis...
).

For the selection of patients for the control group, the defined matching criteria were applied: adult patients, of both genders, who were admitted to the ICU during the study period and did not develop a MRSA infection. The mean age of the cases was also considered when pairing this group.

The control sample was defined according to the number of cases identified in the study period.

Study protocol

Data were collected by the researcher from July to October 2017, through the electronic medical record of the patients provided by the Medical Informatics Center of the hospital. By applying some research filters in these records, a list of hospitalizations containing the name, medical record number and ICU record was obtained.

Then, the electronic medical record called SOUL MV was accessed. This medical record gathers clinical and care information of all patients who developed an infection during the study period. Subsequently, inclusion and exclusion criteria were checked.

For both groups, a form with two parts was used to collect the data. The first part addressed patient identification data (gender, age, length of stay), hospitalization variables (use of mechanical ventilation, tracheostomy, severity, diagnosis at admission, outcomes of hospitalization), use of drains and catheters, procedures performed. The second part addressed the drug/antimicrobial ratio and their respective classes.

The medications considered were vasoactive drugs, sedatives/hypnotics, diuretics, antiepileptics, corticosteroids, antiarrhythmics.

According to the Anatomical-Therapeutic-Chemical Classification of the World Health Organization, the antibacterial agents studied in this work correspond to nine therapeutic groups: Tetracyclines, Penicillins, Cephalosporins/Carbapenems, Sulfonamides/Trimethoprim, Macrolides/ Lincosamides, Aminoglycosides, Quinolones, Glycopeptides/Polymyxins/Imidazoles/Others and Antimycotics for systemic use(2727 World Health Organization (WHO). Collaborating Centre for Drug Statistics and Methodology. ATC Index with DDDs[Internet]. Available from: https://www.whocc.no/atc_ddd_index_ and_guidelines/atc_ddd_index/
https://www.whocc.no/atc_ddd_index_ and_...
).

To classify the patient’s severity, the following standard was used: 1. Stable - requires prophylactic observation of ventilatory and hemodynamic status; 2. Severe stable - changes in vital signs, requires the use of low level of support for maintaining ventilatory, hemodynamic and/or metabolic status, good response to therapy; 3. Severe unstable - changes in vital signs, requires the use of a high level of support for maintaining ventilatory, hemodynamic and/or metabolic status (dialysis) to present the desired response to therapy; 4. Very severe - changes in vital data, requires the use of high level of support for maintaining ventilatory and/ or hemodynamic status; 5. Discharge- patient is in the ICU, but has already been discharged and is waiting for a transfer(2828 Rezende E, Réa-Neto A, David CM, Mendes CL, Dias FS, Schettino G. Consenso brasileiro de monitorização e suporte hemodinâmico-Parte I: métodos e definições. RBTI [Internet]; 2006 [cited 2019 Jun 15] 17(4):278-81. Available from: https://www.amib.org.br/fileadmin/user_upload /amib/2018/ junho/15/ConsesoMonitorizacaoSuporteHemodinamico.pdf
https://www.amib.org.br/fileadmin/user_u...
).

Analysis of results and statistics

In this study, quantitative variables such as age and length of stay were analyzed in terms of means and standard deviations. The other classification variables were presented in tables containing absolute (n) and relative (%) frequencies.

The statistical analysis was conducted in two stages, using the Statistical Package for the Social Sciences (SPSS) 21. In the first stage, the variables that showed statistical significance in the univariate analysis (p<0,20) and were reported in the literature as potential risk factors for ARF were used to adjust the multiple logistic regression model. Values of p < 0.05 (95% CI Confidence Interval) were considered statistically significant.

In the second stage, the double interactions test between exposures included in the multiple model was carried out and the final model was composed only of the main effects of each exposure. In addition, this stage included the association value for predicting the increase in the odds in relation to the dependent variable, based on the knowledge of the relationship with a group of independent variables considered statistically significant.

RESULTS

Based on the inclusion criteria, 122 subjects were selected for the study sample, 61 in each group. Table 1 shows the socio-demographic characteristics of the study participants.

Table 1
Socio-demographic and clinical characteristics of patients in the case and control groups, Botucatu, São Paulo, Brazil, 2019

Most participants were male 65 (53.3%), hypertensive 61 (50%) and their diagnosis was classified as other 49 (40.2%), which included: vascular, urinary, hematological systems and trauma, followed by neurological system 43 (35.2%).

The use of mechanical ventilation was predominant in the case group 57 (93.4%), with a statistically significant difference (p=0.0107). It is observed that, in this group, the number of tracheostomies was also higher (13; 10.6%) (p=0.0083).

Regarding the use of invasive devices, the only one that was statistically significant (p=0,0420) was the indwelling bladder catheter, present in all patients in the case group. The participants in this group were also the most severe (p=0.0003), had a higher incidence of death (p=0.0401) and length of hospitals stay almost tripled in relation to the control group, with a statistically significant difference (p< 0.0001).

Tables 2 describes the intravenous drugs used by the study participants. Hypnotics/Sedatives and antimicrobials were the most used drugs in both groups, 93 (76.23%) and 88 (72.1), respectively. However, the greater use of antibiotics before the diagnosis of MRSA occurred in the case group (p=0.0435).

It was also observed that 39 (63.9%) patients who developed MRSA used up to two antimicrobials, but this showed no statistically significant difference between the groups (p=4549). The class Glycopeptides/ Polymyxins/Imidazoles/Others was the most used by participants who developed a MRSA infection (p=0.0014).

Table 2
Intravenous drugs used by study participants, Botucatu, São Paulo, Brazil, 2019

Table 3 shows the data related to the logistic regression analysis of the variables that were statistically associated with the development of MRSA infection. It is observed that the Very severe state (OR=65.697; CI=3.726–4.808; p=0.0018) and length of stay (OR=1.190;CI=0.952 -1.031; p=0.0285) stood out as risk factors for MRSA infection. The use of antimicrobials was a protective factor (OR= 0.047; CI=0.028-0.122; p=0.0024).

Table 3
Logistic regression of risk factors associated with the development of Methicillin-resistant Staphylococcus Aureus infection, Botucatu, São Paulo, Brazil, 2019

DISCUSSION

In this study, the logistic regression showed that the use of antimicrobials was a protective factor. It should be noted that most patients in the control group received some type of antimicrobial and did not develop a MRSA, corroborating this evidence.

This data must be analyzed in detail case by case, since it is known that the indiscriminate use of antibiotics can increase the patient’s resistance to pathogens and decrease the desired therapeutic response later. Once again, the importance of studies addressing specific antimicrobials should be emphasized, as they allow the development of treatment protocols that are more efficient and lead to a better prognosis(99 Araújo PL, Mendonça AEO, Medeiros RA, Souza Neto VL, Nobre TTX, Costa IKF. Prevalence of health assistance infection in patients hospitalized in intensive therapy unit. Enferm Global [Internet]; 2018 [cited 2020 Jan 20] 52:304-315. Available from: http://scielo.isciii.es/pdf/eg/v17n52/en_1695-6141-eg-17-52-278.pdf
http://scielo.isciii.es/pdf/eg/v17n52/en...
).

Methicillin-resistant Staphylococcus aureus is an important cause of infections worldwide, and an increasingly pressing problem in Latin America(2929 Rodríguez-Noriega E, Seas C, Guzmán-Blanco M, Mejía C, Alvarez C, Bavestrello L, et al. Evolution of methicillin-resistant Staphylococcus aureus clones in Latin America. Int J Infect Dis[Internet]. 2010[cited 2019 Jun 15];14(7):e560-6. Available from: https://www.ncbi.nlm.nih.gov/pubmed/20047848
https://www.ncbi.nlm.nih.gov/pubmed/2004...
). In the clinic, the diagnosis is based on epidemiological information, clinical symptoms and the characterization of the MRSA lineage(3030 Zurita J, Mejía C, Guzmán-Blanco M. Diagnóstico e teste de sensibilidade para Staphylococcus aureus resistente à meticilina na América Latina. Braz J Infect Dis. 2010;14(Suppl-2):97-106. doi: 10.1590/S1413-86702010000800005
https://doi.org/10.1590/S1413-8670201000...
).

In this context, strengthening the surveillance can provide more reliable data, which can contribute to the establishment of protocols that include hospital sectors other than the ICU, reducing the number of patients infected and, consequently, reducing mortality. Therefore, systematic surveillance can be the best way to detect the infection and provide an early treatment, which can avoid worsening of the underlying disease and, consequently, prevent the patient’s death.

In this context, it is worth emphasizing the importance of the isolation measures for infected patients, which include hand washing with antiseptics, isolation, use of own materials and subsequent disinfection or disposal, personal protective equipment for professionals, and decolonization measures such as: bathing using chlorhexidine on the body and hair, use of 2% mupirocin where MRSA was isolated, exchange of invasive catheters and monitoring of colonization by the pathogen(3131 Qiao F, Huang W, Cai L, Zong Z, Yin W. Methicillin-resistant Staphylococcus aureus nasal colonization and infection in an intensive care unit of a university hospital in China. J Int Med Res. 2018; 46(9):3698-708. doi: 10.1177/0300060518777812
https://doi.org/10.1177/0300060518777812...
).

However, there are studies showing that the discontinuation of contact precautions for patients with MRSA, along with the daily chlorhexidine bath, is associated with increased MRSA infection(3232 Webster J, Osborne S. Preoperative bathing or showering with skin antiseptics to prevent surgical site infection. Cochrane Database Syst Rev. 2015;(2):CD004985. doi: 10.1002/14651858.CD004985.pub5
https://doi.org/10.1002/14651858.CD00498...
). A randomized clinical trial carried out with 45 patients undergoing hip arthroplasty showed that chlorhexidine bathing should be recommended with caution as a strategy to reduce surgical site infection(3333 Franco LMC, Almeida AGI, Duarte GMH, Lamounier L, Pinto TS, Pereira PFS, et al. Efeitos do banho pré-operatório na prevenção de infecção cirúrgica: estudo clínico piloto. Rev Min Enferm [Internet]; 2017 [cited 2019 Jun 15]:212017. Available from: https://pesquisa.bvsalud.org/portal/resource/pt/bde-32207
https://pesquisa.bvsalud.org/portal/reso...
).

Health care-associated infections are a serious public health problem because adverse events associated with health care are frequent, lead to high morbidity and mortality, and have a direct impact on patient safety(3434 Costa MMM. Efeitos de um ciclo de melhoria da qualidade nacional aplicado à estruturação das ações de prevenção das infecções relacionadas à assistência à saúde em hospitais brasileiros [Dissertação][Internet]. 2016[cited 2019 Jun 15]. 125f. Available from: https://repositorio.ufrn.br/jspui/handle/123456789/21933
https://repositorio.ufrn.br/jspui/handle...
).

A recent systematic review that analyzed 21 articles showed that the risk of MRSA infections among burn patients admitted to the ICU is high (55%) and suggest that, in addition to appropriate hand hygiene and adequate wound care while handling these patients, further research should be carried out to identify the risk factors associated with this infection(3535 Khan TM, Kok YL, Bukhsh A, Lee LH, Chan KG, Goh BH. Incidence of methicillin resistant Staphylococcus aureus (MRSA) in burn intensive care unit: a systematic review. Germs [Internet]; 2018 [cited 2019 Jun 15];8(3):113-125. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6141222/.
https://www.ncbi.nlm.nih.gov/pmc/article...
).

In this study, most patients who acquired a MRSA infection were male (60.6%) and the mean age was 62.8 years. These data were corroborated in a study conducted in Bogotá with 204 patients who acquired this infection in the ICU(3636 Barrero LI, Castillo JS, Leal AL, Sánchez R, Cortés JA, Álvarez CA, et al. Impacto económico de la resistencia a la meticilina en pacientes con bacteriemia por Staphylococcus aureus en hospitales de Bogotá. Bioméd [Internet]; 2014 [cited 2019 Jun 15];34:345-53. Available from: http://www.scielo.org.co/ pdf/bio/v34n3/v34n3a05.pdf
http://www.scielo.org.co/ pdf/bio/v34n3/...
).

The groups studied showed significant differences in relation to clinical data, such as severity, length of stay and outcome. The rate of MRSA infection among patients considered very severe was 50.8%, which was corroborated in a study carried out in Bogotá, where mortality rate among patients with the infection was 53%, length of stay increased and there was a 70% increase in costs associated with MRSA(3636 Barrero LI, Castillo JS, Leal AL, Sánchez R, Cortés JA, Álvarez CA, et al. Impacto económico de la resistencia a la meticilina en pacientes con bacteriemia por Staphylococcus aureus en hospitales de Bogotá. Bioméd [Internet]; 2014 [cited 2019 Jun 15];34:345-53. Available from: http://www.scielo.org.co/ pdf/bio/v34n3/v34n3a05.pdf
http://www.scielo.org.co/ pdf/bio/v34n3/...
).

MRSA was significantly associated with mortality in patients who developed bacteremia caused by Staphylococcus aureus, as evidenced by a study conducted with 255 episodes S. aureus bacteremia(3737 Yilmaz M, Elaldi N, Balkan İİ, Arslan F, Batırel AA, Bakıcı MZ, et al. Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study. Ann Clin Microbiol Antimicrob [Internet]; 2016 [cited 2019 Jun 15];15:7. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748515/
https://www.ncbi.nlm.nih.gov/pmc/article...
). This data was corroborated in a study carried out in a Brazilian university hospital(3838 Porto JP, Santos RO, Gontijo Filho PP, Ribas RM. Active surveillance to determine the impact of methicillin resistance on mortality in patient with bacteremia and influences of the use of antibiotics on the development of MRSA infection. Rev Soc Bras Med Trop [Internet]; 2013 [cited 2019 Jun 15];46(6):713-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24474012
https://www.ncbi.nlm.nih.gov/pubmed/2447...
), comparing risk factors among patients with MRSA and patients with methicillin-sensitive Staphylococcus aureus infection.

In the present study, the use of MV, tracheostomy and urinary catheter was higher in the group of patients who acquired a MRSA infection. However, this was not a risk factor associated with infection, as evidenced in another study on the theme(3838 Porto JP, Santos RO, Gontijo Filho PP, Ribas RM. Active surveillance to determine the impact of methicillin resistance on mortality in patient with bacteremia and influences of the use of antibiotics on the development of MRSA infection. Rev Soc Bras Med Trop [Internet]; 2013 [cited 2019 Jun 15];46(6):713-8. Available from: https://www.ncbi.nlm.nih.gov/pubmed/24474012
https://www.ncbi.nlm.nih.gov/pubmed/2447...
).

A recent study showed that MRSA colonization significantly increases the risk of subsequent MRSA infection. In addition, a significant proportion of infections by this microorganism can occur after hospital discharge(3939 Nelson RE, Evans ME, Simbartl L, Jones M, Samore MH, Kralovic SM, et al. Methicillin-resistant Staphylococcus aureus Colonization and Pre-and Post-hospital Discharge Infection Risk. Clin Infect Dis [Internet]; 2019 [cited 2019 Jun 15];68(4):545-553. Available from: https://www.ncbi.nlm.nih.gov/pubmed/30107401
https://www.ncbi.nlm.nih.gov/pubmed/3010...
).

Regarding the antimicrobials used to treat patients with MRSA, there was a high prevalence of the use of Glycopeptide/Polymyxin/Imidazole/Derivatives/others and Beta-lactams in both groups.

The combination of imipenem and vancomycin is widely indicated for the treatment of MRSA. The combination of two antimicrobials was the most prevalent in the present investigation. This finding can be attributed to the limited therapeutic effect of vancomycin used alone in MRSA infections in conjunction with gram-negative bacteria. On the other hand, the association with imipenem broadens the spectrum of antimicrobial action and allows lower doses of vancomycin to be used, which leads to less toxicity and shorter treatment time(4040 Jones RN. Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep, bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains. Clin Infect Dis[Internet]. 2006[cited 2019 Jun 15];42(Suppl-1):S13-24. Available from: https://www.ncbi.nlm.nih.gov/pubmed/16323115
https://www.ncbi.nlm.nih.gov/pubmed/1632...
).

Thus, believing that nurses have a primary role in decision-making and promote continuous surveillance, prevention and health promotion actions at all levels of health care, this study can contribute to minimize some risk factors and suggest new approaches that can be implemented to reduce the number of cases of MRSA infection.

However, a study carried out in Nigeria with 80 health professionals showed that, even though knowledge and awareness of infection control among ICU health professionals are good, practice is unsatisfactory. One of the measures was to optimize simple practices, such as hand washing, which has a major impact in the prevention of nosocomial infection(4141 Adegboye MB, Zakari S, Ahmed BA, Olufemi GH. Knowledge, awareness and practice of infection control by healthcare workers in the intensive careunits of a tertiary hospital in Nigeria. Afr Health Sci [Internet]; 2018 [cited 2019 Jun 15];18(1):72-78. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6016975/
https://www.ncbi.nlm.nih.gov/pmc/article...
).

Study limitations

The results of this study reflect the reality of a single intensive care unit of a public hospital, which limits the generalization of the results, despite of the sample size. Lack of records in electronic medical records and absence of patient’s severity information were observed. In addition, deaths certificates were not evaluated.

Contributions to the nursing, health or public policy areas

It is believed that the results presented here can support health care practice in the institution where the research was conducted, through the establishment of care protocols for the early detection and prevention of MRSA infections and the development of further multicenter studies.

Furthermore, it can contribute to teaching and research in nursing, as it provides new knowledge and theoretical basis for the multifaceted management of the care required for the prevention of HAIs among critically ill patients in intensive care units.

CONCLUSION

MRSA infection in the ICU is complex and multifactorial. It affects older adults, with urinary catheter, mechanical ventilation and tracheostomy and predisposes to death. It was associated with length of stay and severity of patients.

The use of antimicrobials was a protective factor. In this context, the importance of nurses in continuing education actions, supervision of direct patient care and adequate working conditions are actions to prevent and control this type of infection.

  • FUNDING
    National Council for Scientific and Technological Development (CNPQ), Scientific Initiation.

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Edited by

EDITOR IN CHIEF: Antonio José De Almeida Filho
ASSOCIATE EDITOR: Mitzy Reichembach

Publication Dates

  • Publication in this collection
    07 Sept 2020
  • Date of issue
    2020

History

  • Received
    17 Sept 2019
  • Accepted
    18 Feb 2020
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