Prevalence of methicillin-resistant Staphylococcus aureus in a University Hospital in the South of Brazil

Methicillin-resistant Staphylococcus aureus (MRSA) stand out as one of the main agents causing nosocomial and community infections. This retrospective study aimed to analyze the MRSA predominance in a university hospital in the south of Brazil and it was carried out for five years (from 2007 to 2011). 616 MRSA (33,3% of the total) were isolated and an important reduction in the MRSA predominance was observed along the study. Although it was registered a reduction in the MRSA predominance, male adult patients (41-70 years old), who were in the Medical Clinic and Adult ICU, had the highest infection rates and concerning MRSA isolates rates, these were higher in blood and tracheal aspirates. In conclusion, studies of this type are becoming relevant to recognize pathogens like MRSA and to determine its predominance.


INTRODUCTION
Staphylococcus aureus is worldly known as one of main responsible agents, which cause a wide number of infections including septicemia, pneumonia, skin and soft tissues infections (Dong et al., 2013).It is considered an important etiological agent in nosocomial infections as well as in ones acquired in the community (François et al., 2007).The occurrence of methicillin-resistant Staphylococcus aureus strains has become a great challenge due to its prevalence in hospital environment infections as well as in community infections (Boucher, Corey, 2008).
MRSA was firstly reported in hospitals (healthcareassociated MRSA -HA-MRSA) in the United Kingdom in 1961 and after that, it spread to many other health institutions all over the world (Jevons, 1961;Deurenberg et al., 2007).Regarding hospital environment, the MRSA colonization or infection was associated to risk factors like recent surgery, in hospital patients, chronic diseases and presence of a catheter among others.
After two decades, the first MRSA cases acquired in the community were reported (CA-MRSA) (Saravolatz et al., 1982;Saravolatz, Pohlod, Arking, 1982) and since 1990 an increase in the infection occurrence caused by CA-MRSA has been reported in many countries (Deurenberg et al., 2007;Skov et al., 2012).The emergence of infections caused by this microorganism, when risk factors are absent, marked the beginning of a public health problem (Sdougkos et al., 2008).
In Europe, the MRSA are well known among the multiresistant bacteria, which are the most involved in infections related to health assistance (European Centre for Disease Prevention and Control, European Medicines Agency, 2009).Considering United States and Latin America, this microorganism constitutes the main bacterial agent involved in nosocomial infections also presenting a growing involvement in the prevalence of infections in the community (Wallin, Hern, Frazee, 2008;Guzmán-Blanco et al., 2009).
This study aims to determine the MRSA prevalence in different clinical samples making use of a retrospective analysis of bacteriological tests carried out in a tertiary university hospital.

MATERIAL AND METHODS
This retrospective study was carried out through a research in the Microbiology Laboratory database of the University Hospital of Santa Maria (HUSM), which has 37 beds for intensive care and 291 beds for admission, in the city of Santa Maria, south of Brazil.This hospital is a tertiary one, which provides medical assistance for 30 cities from the central region of Rio Grande do Sul (RS) state.
The data of all cultures where S. aureus growing was observed from January 1 st , 2007 to December 31 st , 2011 were analyzed.

Inclusion criteria of MRSA samples
It was considered as MRSA all S. aureus isolates, which presented resistance to oxacillin and/or cefoxitin.Such consideration was carried out through conventional phenotypic methodology, through disk diffusion technique (Kirby-Bauer), and the isolates were confirmed through automated phenotypic methodology (MicroScan® -Siemens), according to the standards established by the Clinical and Laboratory Standards Institute (CLSI) prevailing in each year.
In this study, only the first bacterial sample of S. aureus isolates from each patient was used.

Ethics Committee
This study was submitted to the Reseach Ethics Committee (CEP) of the Federal University of Santa Maria and it was approved under the number 0117.0.243.000-08.

Statistical Analysis
The experimental data were evaluated through Chi-Square test where a value of p<0,05 was considered statistically significant.

RESULTS
This study was carried out for five years (2007 to 2011).During this time 1.852 samples of S. aureus were isolated and 616 (33.3%) were oxacillin-resistant (MRSA).The MRSA prevalence as well as the oxacillinsensitive S. aureus (MSSA) according to each year can be observed on Table I.The annual MRSA prevalence is shown on Figure 1.
The distribution of MRSA isolates was predominantly in male patients (Figure 2).
Regarding age groups during all study period, it was registered a bigger predominance among patients with ages between 41-70 years (258/594) (Table II).The age of the patient was not registered in 22 cases.
The hospital units, which registered bigger predominance of MRSA isolates, were arranged in a descending order, as it can be seen on Table III

DISCUSSION
MRSA are the main responsible agents, which cause nosocomial infections all over the world (Japoni et al., 2010).In Brazil, the MRSA prevalence varies according to the regions and to the clinical material from which this important pathogen is isolated, presenting rates between 44% to 56% (Ferreira et al., 2009;Carvalho, Mamizuka, Gontijo Filho, 2010).In the European Community, the MRSA reach different rates among its countries having less than 1% to more than 24% (Dulon et al., 2011; European Centre for Disease Prevention and Control, European Medicines Agency, 2009), however, in the USA these rates can reach 38.2% (Jarvis, Jarvis, Chinn, 2012).
During the five years of study, the MRSA prevalence   average rate at HUSM was 33.3% and similar rate to the one found in this work with an index equal or higher than 25% is found in data from the European Antimicrobial Resistance Surveillance System (2009), in countries like Greece, Italy, Bulgary, Turkey and Spain.
It was also found a significant reduction (approximately 40%) in the MRSA prevalence rates decreasing its percentage of 43.4% in 2007 to 27.5%, in 2011 (p<0.05).Such reduction at HUSM was due possibly to the work of the Committee on Hospital Infection Control, which since 2006 has established actions as discontinuation of antibiotic therapy and professional training and a more rigid antimicrobial distribution aiming at reducing these rates.Programs of prevention and control of the MRSA carried out in some hospitals in the European Community have become priority to public health and have reached satisfactory results due to the reduction in the MRSA infection rates in these countries (Köck et al., 2010).
When genders are compared, it was observed that a small prevalence of MRSA infections happen with men.Such data was registered in all years of the study period (Figure 2) having an average rate of 60.6%.Such results are similar to the ones found by Mahmood et al. (2010) in Pakistan between 2005 and 2009 and by Jarvis, Jarvis, Chinn (2012) in the USA.Both teams verified that 58% and 52.2% of patients hospitalized with MRSA were men respectively.
Although the majority of the infection cases happen with 41 to 70 year-old adults (Table II), in 2009 was registered a higher number of MRSA isolates in adolescents and young adults (11-40 year-old patients).The highest infection predominance in adults and mainly with elderly people is due to their vulnerability because they are more frequently exposed to excessive manipulation and invasive procedures (Souza, Figueiredo, 2008).Patients infected by MRSA belonging to the same age group were also reported in other studies (Mahmood et al., 2010;Souza, Figueiredo, 2008).
According to the hospital unit, the Medical Clinic followed by the Adult ICU were the ones which presented the highest index, representing respectively 16.3% and 15.1% of the total MRSA isolates.The Ambulatory (13.0%), Adult Emergency (12.7%) and Clinical Surgery (12.5%) also reached relevant MRSA isolates rates at HUSM.Other authors in Brazil as well as in the USA also report higher MRSA prevalence in ICUs, as it was reported in our study (Souza, Figueiredo, 2008;Jarvis, Jarvis, Chinn, 2012).This data is justified by the fact that patients in ICUs are frequently submitted to medical and therapeutic interventions, it is applied a big number of invasive medical devices and besides it is employed multiple therapies that can trigger the development of a MRSA infection (Verdier et al., 2006).Furthermore, data from the National Nosocomial Infections Surveillance of the Center for Disease Control and Prevention (CDC) in the USA show that since 1999, the MRSA prevalence rates are beyond 50% among patients in ICUs (Moura et al., 2007).
The clinical materials, which presented the biggest number of MRSA isolates were blood, tracheal aspirates, urine, sputum, secretion of surgical wound and secretion of lower limb.In the USA and in some European countries, the incidence of bacteremia caused by MRSA has increased in the last years (Shorr, Lodise, 2006).According to a study carried out in Iran, in 2007, Japoni et al. (2010) reported a bigger number of MRSA isolates in blood, sputum and wound samples while Mahmood et al. (2010) reported a bigger incidence in sputum samples.In Brazil, Souza, Figueiredo (2008) in 2008, at the Regional University Hospital of Maringá found a bigger incidence of MRSA isolates in catheter tips and tracheal secretion.

CONCLUSION
This research found out that the MRSA prevalence rate showed substantial reduction from 2007 to 2011 and such reduction is possibly related to the collective construction of a MRSA prevention and control "bundle" guided by the practical criteria of the Committee on Hospital Infection Control at HUSM.
Infections caused by MRSA constitute an important world challenge in the public health system knowledge concerning MRSA prevalence rates at the University Hospital of Santa Maria together with the effective actions, concerning MRSA infections, registered by the Committee on Hospital Infection Control has a direct impact on the health system of our country in terms of morbidity, mortality and financial costs.

FIGURE 2 -
FIGURE 2 -Distribution of patients with infections caused by MRSA at HUSM from 2007 to 2011 according to gender.

FIGURE 3 -
FIGURE 3 -Distribution of clinical samples with more prevalence of MRSA isolates at HUSM from 2007 to 2011.

TABLE I -
Prevalence of MRSA and MSSA isolates at HUSM, from 2007 to 2011

TABLE II -
Age groups of MRSA isolates (2007 to 2011) at HUSM

TABLE III -
MRSA isolates according to Hospital Units, in the years of 2007 to2011