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Staphylococcus aureus and the oxacillin sensitivity profile in hospitalized people with HIV/AIDS

Staphylococcus aureus y el perfil de sensibilidad a la oxacilina en personas viviendo con vih/sida hospitalizadas

Abstract

Objective

Analyze nasal colonization by oxacillin-sensitive and oxacillin-resistant Staphylococcus aureus in people with HIV/AIDS (PWHA) at days 1 and7 of hospitalization.

METHOD

A prospective observational study conducted in a hospital in the countryside of the state of São Paulo. Nasal swab samples were collected and analyzed through microbiological identification, at days 1 and 7 of hospitalization of PWHA, between August 2011 and January 2014. Data were analyzed via IBM SPSS(r), version 20.0.

RESULTS

Nasal secretion samples were collected from 187 (50.1%) PWHA at days 1 and 7 of hospitalization. Of these, Staphylococcus aureus was identified in 64 (34.2%) PWHA.

CONCLUSION

At day 1 of hospitalization, 27 PWHA were identified with Staphylococcus aureus; 27 PWHA presented colonization by Staphylococcus aureus at days 1 and 7, and 10 PWHA only at day 7. Of 64 PWHA colonized by Staphylococcus aureus, the susceptibility profile of isolated Staphylococcus aureus was oxacillin-resistant in 25 PWHA.

Descriptors
HIV Infections; Hospitalization; Staphylococcus aureus; Oxacillin

Resumen

OBJETIVO

Analizar la colonización nasal por Staphylococcus aureus sensibles y resistentes a la oxacilina de personas viviendo con VIH/Sida (PVVS) el primer y séptimo día de estancia hospitalizar.

MÉTODO

Estudio prospectivo observacional, realizado en un hospital del interior del Estado de São Paulo. Fueron recogidas y analizadas, mediante identificación microbiológica, muestras de swab nasal el primer y el séptimo día de estancia hospitalaria de PVVS, en el período de agosto/2011 a enero/2014. Se realizó el análisis de los datos mediante el IBM SPSS(r), versión 20.0.

RESULTADOS

En 187 (50,1%) PVVS, fueron recogidas muestras de secreción nasal el primer y séptimo día de estancia hospitalaria. De esas, en 64 (34,2%) fue identificado Staphylococcus aureus.

CONCLUSIÓN

El primer día de estancia se observó 27 PVVS colonizadas por Staphylococcus aureus; en 27 PVVS hubo la persistencia de la colonización por Staphylococcus aureus el primer y el séptimo día; en 10 PVVS, solo el séptimo día. De las 64 PVVS colonizadas por Staphylococcus aureus, en 25 el perfil de susceptibilidad del Staphylococcus aureus aislado fue resistente a la oxacilina.

Descriptores
Infecciones por VIH; Hospitalización; Staphylococcus aureus; Oxacilina

Resumo

OBJETIVO

Analisar a colonização nasal por Staphylococcus aureus sensíveis e resistentes à oxacilina de pessoas vivendo com HIV/aids (PVHA) no primeiro e no sétimo dia de internação hospitalar.

MÉTODO

Estudo prospectivo observacional realizado em um hospital do interior paulista. Foram coletadas e analisadas, por meio de identificação microbiológica, amostras de swab nasal no primeiro e no sétimo dia de internação hospitalar de PVHA, no período de agosto/2011 e janeiro/2014. A análise dos dados foi realizada por meio do IBM SPSS(r), versão 20.0.

RESULTADOS

Em 187 (50,1%) PVHA foram coletadas amostras de secreção nasal no primeiro e sétimo dia de internação. Destas, em 64 (34,2%) foi identificado Staphylococcus aureus.

CONCLUSÃO

No primeiro dia de internação observou-se 27 PVHA colonizadas por Staphylococcus aureus; em 27 PVHA houve a persistência da colonização por Staphylococcus aureus no primeiro e no sétimo dia; em 10 PVHA, somente no sétimo dia. Das 64 PVHA colonizadas por Staphylococcus aureus, em 25 o perfil de suscetibilidade do Staphylococcus aureus isolado foi resistente à oxacilina.

Descritores
Infecções por HIV; Hospitalização; Staphylococcus aureus; Oxacilina

Introduction

Human beings are natural reservoirs of Staphylococcus aureus, a bacterium that is especially found in the nose, vagina, pharynx and/or injured skin surfaces11 Anstead GM, Cadena J, Javeri H. Treatment of infections due to resistant Staphylococcus aureus. Methods Mol Biol. 2014;1085:259-309.. Once natural protection barrier is past, the microorganism can access underlying layers of the skin and, in favorable conditions, it may cause an infection22 Van HSJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25(2):362-86.-33 Weintrob A, Bebu I, Agan B, Diem A, Johnson E, Lalani T, et al. Randomized, double-blind, placebo-controlled study on decolonization procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-infected adults. PLoS One. 2015;10(5):e0128071..

An infection situation can be very serious in immunocompromised patients, such as those with the human immunodeficiency virus (HIV), serious burns and cancer, increasing the morbimortality rate, length of hospital stay and healthcare costs44 Lambert ML, Suetens C, Savey A, Palomar M, Hiesmayr M, Morales I, et al. Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet Infect Dis. 2011; 11(1):30-8..

Infections caused by Staphylococcus aureus have been considered the major cause of morbimortality of people living with HIV/AIDS (PWHA), due to virulence factor of this microorganism and its resistance to antibiotics. Methicillin-resistant Staphylococcus aureus (MRSA) was first described in Europe by Jevons in 1961 as a nosocomial pathogen. Since then, microbial resistance is one of the major concerns of public health, with serious economic, social and political implications that affect individuals globally, going beyond environmental and ethnical boundaries55 Reinato LAF, Pio DPM, Lopes LP, Pereira FMV, Lopes AER, Gir E. Nasal colonization with Staphylococcus aureus in individuals with HIV/AIDS attended in a Brazilian Teaching Hospital. Rev Latino Am Enfermagem. 2013;21(6):1235-9..

People with HIV/AIDS present higher incidence of Staphylococcus aureus when compared to non-infected people44 Lambert ML, Suetens C, Savey A, Palomar M, Hiesmayr M, Morales I, et al. Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet Infect Dis. 2011; 11(1):30-8..Thus, HIV infection is a risk factor for colonization and infection by MRSA66 Kotpal R, Krishna PS, Bhalla P, Dewan R, Kaur R. Incidence and risk factors of nasal carriage of Staphylococcus aureus in HIV-infected individuals in comparison to HIV-uninfected individuals: a case-control study. J Int Assoc Provid AIDS Care. 2016;15(2):141-7.

7 Oliva A, Lichtner M, Mascellino MT, Iannetta M, Ialungo AM, Tadadjeu Mewamba S, et al. Study of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a population of HIV-negative migrants and HIV-infected patients attending an outpatient clinic in Rome. Ann Ig. 2013;25(2)99-107.
-88 Lee LK, Win MK, Veeraraghavan MA, Wong CS, Chow AL, Leo YS. Short communication: risk factors for methicillin-resistant Staphylococcus aureus colonization among HIV patients at hospital admission. AIDS Res Hum Retroviruses. 2013;29(5):796-8..

Despite the outstanding progress with the antiretroviral therapy for HIV patients, several undesirable situations still require hospitalization, exposing them to the nosocomial microbiota. The main causes of PWHA hospitalization include: gastrointestinal diseases, bacterial infections and cardiovascular diseases99 Crum-Cianflone NF, Grandits G, Echols S, Ganesan A, Landrum M, Weintrob A, et al. Trends and causes of hospitalizations among HIV-infected persons during the late HAART era: what is the impact of CD4 counts and HAART use? J Acquir Immune Defic Syndr. 2010;54(3):248-57..The hospitalization process requires interventions that change the natural microbiota of the patient, due to an aggravated health condition, like systemic diseases or use of medication, invasive procedures or site contamination.

A study conducted in Ireland demonstrated that the effect of an early MRSA detection facilitates screening and early patient isolation, leading to reduced cross infection1010 Creamer E, Dolan A, Sherlock O, Thomas T, Walsh J, Moore J, et al. The effect of rapidscreening for methicillin-resistant Staphylococcusaureus (MRSA) on the identification and earlier isolation of MRSA-positive patients. Infect Control Hosp Epidemiol. 2010;31(4):374-81.. Based on that, identifying colonization by multidrug-resistant microorganisms at hospital admission of PWHA allows the adoption of clinical measures, such as: isolation and decolonization techniques to prevent microorganism dissemination and, consequently, a possible infection.

It is important to recognize the particularities involving PWHA when seeking care individualization to these patients. The nosocomial environment can have a direct influence on multidrug-resistant microorganism dissemination in this population. Thus, the objective of this study was to analyze nasal colonization by oxacillin-sensitive and oxacillin-resistant Staphylococcus aureus in PWHA at days 1 and 7 of hospitalization, correlating it to sociodemographic and clinical findings. This study assumes that a period of 7 days or more of hospitalization can change the nasal colonization of PWHA in relation to the presence or not of oxacillin-sensitive or oxacillin-resistant Staphylococcus aureus.

Method

This is a prospective observational study conducted in two specialized units that provide care to patients with infectious diseases of a university hospital in the countryside of the state of São Paulo.

This study was approved by the Ethics Committee of the Escola de Enfermagem de Ribeirão Preto da USP, observing the recommendations in Resolution 196/96 of the Brazilian Health Council (Protocol nº 1304/2011).

This study used convenience sampling and included all participants who met the inclusion criteria: being 18 years old and over, being aware of the HIV/AIDS infection diagnosis and providing material collection at days 1 and 7 of hospitalization .The exclusion criteria were: people living with HIV/AIDS using any ventilation device and/or presenting a clinical condition preventing material collection. For participants with more than one hospitalization period, this study considered only the first one.

The participants were selected by collection assistants, who received a specific training from August 2011 to January 2014. At day 1 of hospitalization, the patient was invited to participate and received information regarding the ethical aspects of this study. After the patient approval, the participant signed an informed consent form.

Sociodemographic and clinical data were collected through individual interviews and from clinical records of the patient. Nasal secretion samples were obtained with a dry swab with sterile Stuart medium (COPAN(r)), rubbed on both nares, at day 1 of hospitalization to check whether the PWHA was already colonized by oxacillin-sensitive or oxacillin-resistant Staphylococcus aureus, and at day 7 of hospitalization to check for oxacillin-sensitive or oxacillin-resistant Staphylococcus aureus, as compared to the condition identified at day 1. The swabs were kept at ambient temperature (30ºC) in plastic capped containers that were sent to the microbiological analysis laboratory within 24 hours of collection, where they were placed on agar blood and mannitol plates.

The isolation and phenotypic identification of Staphylococcus aureus were performed using an automated method, with the help of Vitek(r) (BioMérieuxTM) system cards. Resistance to antimicrobials was tested using (BioMérieuxTM) AST-P585 card. When a nasal colonization by Staphylococcus aureus was confirmed in study participants, the Hospital Infection Control Commission was informed, which in turn, informed the patient's physician, who analyzed with the commission the institution's decolonization protocol prescription.

Data were organized on a spreadsheet produced with Microsoft Office Excel for Windows 7 using double entry and were validated subsequently. The final spreadsheet was transported and analyzed using IBM SPSS(r), version 20.0 for Windows, performing operations of new variable creation, categorization and grouping, and then data analysis of descriptive and analytical statistics, using the chi-square test, p value of 0.05.

Results

Of 373 participants analyzed in the study period, 187 (50.1%) were eligible and met the inclusion criteria; in 123 (65.7%), the cultures were negative at day 7 (Table 1).

Table 1
Distribution of PWHA according to the nasal colonization by oxacillin-sensitive or oxacillin-resistant Staphylococcus aureus at days 1 and 7 of hospitalization - Ribeirão Preto, SP, Brazil, 2011-2014.

Of 64 (34.2%) participants with positive culture to Staphylococcus aureus, 27 (42.2%) showed persistent microorganism at days 1 and 7 of hospitalization, and three (4.7%) presented a different profile of oxacillin sensitivity, as at day 7, oxacillin-resistant Staphylococcus aureus was observed. Seven (10.9%) participants presented Staphylococcus aureus only at day 7 of hospitalization; however, the profile of susceptibility showed oxacillin-resistant microorganism.

Regarding participant characterization, 59.4% were male. The predominant age was ≥ 40 and ≤ 59 years in 49.7% of the sample. In terms of educational attainment, 39.0% had not completed higher education. The clinical diagnosis of HIV infection 5 years or less was observed in 38.5% of the participants; 77.0% were submitted to an invasive procedure during hospitalization; 59.9% presented detectable viral load for HIV; 69.0% presented CD4+T lymphocyte counts of 350 cell/mm3 or less; 72.2% were taking an antimicrobial; 58.8% did not have the antiretroviral therapy prescribed during hospitalization (Table 2).

Table 2
Distribution of PWHA at day 7 of hospitalization according to the nasal colonization by Staphylococcus aureus and sociodemographic and clinical variables - Ribeirão Preto, SP, Brazil, 2011-2014.

The chi-square test was used, p value of 0.05, correlating the following variables: sex, sexual relation in the last6 months, use of antibiotics during hospitalization, antiretroviral therapy prescribed during hospitalization and invasive procedure during hospitalization with nasal colonization by Staphylococcus aureus (Table 3).

Table 3
Association of PWHA at day 7 of hospitalization according to the nasal colonization by Staphylococcus aureus and behavioral and clinical variables - Ribeirão Preto, SP, Brazil, 2011-2014.

Discussion

This study analyzed the nasal mucosa as the site of colonization by Staphylococcus aureus. A case-control study conducted in Singapore, which attempted to identify MRSA in people with HIV/AIDS at hospital admission, showed the main site of colonization by this microorganism were the nares of participants77 Oliva A, Lichtner M, Mascellino MT, Iannetta M, Ialungo AM, Tadadjeu Mewamba S, et al. Study of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a population of HIV-negative migrants and HIV-infected patients attending an outpatient clinic in Rome. Ann Ig. 2013;25(2)99-107..

In this study, male PWHA presented higher rates of nasal colonization by Staphylococcus aureus, in agreement with the findings from a study conducted in Barcelona to investigate the prevalence of MRSA in patients with HIV/AIDS1111 Imaz A, Camoez M, Di Yacovo S, Gasch O, Dominguez MA, Vila A, et al. Prevalence of methicillin-resistant Staphylococcus aureus colonization in HIV-infected patients in Barcelona, Spain: a cross-sectional study. BMC Infect Dis. 2015; 15:243..

Monitoring the dissemination of Staphylococcus aureus in this population with HIV/AIDS contributes to infection control and prevention programs and the survival of these patients55 Reinato LAF, Pio DPM, Lopes LP, Pereira FMV, Lopes AER, Gir E. Nasal colonization with Staphylococcus aureus in individuals with HIV/AIDS attended in a Brazilian Teaching Hospital. Rev Latino Am Enfermagem. 2013;21(6):1235-9.; for this reason, surveillance policies are viable for patients at risk for colonization and infection by multidrug-resistant microorganisms. It is essential to identify this condition of the patient at hospital admission and monitor the patient during hospitalization.

The risk factors indicated as predisposing factors for the susceptibility of people with HIV/AIDS to MRSA are: CD4+T lymphocyte count below 500 cell/mm3, HIV viral load of 400 copies/ml or above, use of injectable drugs, old age, prior hospitalization and invasive procedures77 Oliva A, Lichtner M, Mascellino MT, Iannetta M, Ialungo AM, Tadadjeu Mewamba S, et al. Study of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a population of HIV-negative migrants and HIV-infected patients attending an outpatient clinic in Rome. Ann Ig. 2013;25(2)99-107.,1212 Vyas KJ, Shadyab AH, Lin CD, Crum-Cianflone NF. Trends and factors associated with initial and recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections among HIV-infected persons: an 18-year study. J Int Assoc Provid AIDS Care. 2014;13(3):206-13.. Based on that, most participants of this study presented most risk factors indicated as predisposing factors for colonization by MRSA in this investigated population.

At day 7 of hospitalization, Staphylococcus aureus was observed in 10 (15.6%) participants; of these, seven (70.0%) were oxacillin resistant, similar to a study conducted with long-term hospitalized patients who presented higher prevalence of MRSA when compared to other multidrug-resistant microorganisms1313 Lim CJ, Cheng AC, Kennon J, Spelman D, Hale D, Melican G, Sidjabat HE, Paterson DL, Kong DC, Peleg AY. Prevalence of multidrug-resistant organisms and risk factors for carriage in long-term care facilities: a nested case-control study. J Antimicrob Chemother. 2014;69(7):1972-80..

Another relevant factor is that most participants did not have antiretroviral medications prescribed during hospitalization, but the literature shows one of the main causes of hospitalization of PWHA is their non-adherence to prescribed antiretroviral treatment, causing a greater exposure of these individuals to the nosocomial environment1414 Blatt CR, Citadin CB, Souza FG, Mello RS, Galato D. Avaliação da adesão aos anti-retrovirais em um município no Sul do Brasil. Rev Soc Bras Med Trop [Internet]. 2009 [citado 2016 fev. 05];42(2):131-6. Disponível em: Disponível em: http://www.scielo.br/pdf/rsbmt/v42n2/v42n2a07.pdf
http://www.scielo.br/pdf/rsbmt/v42n2/v42...
-1515 Silva ACO, Reis RK, Nogueira JA, Gir E. Quality of life, clinical characteristics and treatment adherence of people living with HIV/AIDS. Rev Latino Am Enferm. 2014; 22(6):994-1000..

The limitations of this study refer to the lower number of participant follow-up at day 7 of hospitalization versus day 1, due to discharges, refusals or deaths. In addition, a study on prevalence and risk factors for MRSA in people with HIV/AIDS indicates the importance of investigating several sites of possible colonization by Staphylococcus aureus in this population, not only the nares1313 Lim CJ, Cheng AC, Kennon J, Spelman D, Hale D, Melican G, Sidjabat HE, Paterson DL, Kong DC, Peleg AY. Prevalence of multidrug-resistant organisms and risk factors for carriage in long-term care facilities: a nested case-control study. J Antimicrob Chemother. 2014;69(7):1972-80.,1616 Farley JE, Hayat MJ, Sacamano PL, Ross T, Carroll K. Prevalence and risk factors for methicillin-resistant Staphylococcus aureus in an HIV-positive cohort. Am J Infect Control. 2015;43(4):329-35..

Conclusion

Of 187 (100%) participants who provided nasal secretion samples at days 1 and 7 of hospitalization, 64 (34.2%) presented nasal colonization by Staphylococcus aureus: 27 (14.4%) at day 1, 10 (5.3%) at day 7, and 27 (14.4%) at both days 1 and 7, characterizing persistent colonization by Staphylococcus aureus.

Resistance to oxacillin was observed in 25 (13.3%) participants; 10 (5.3%) of these only at day 7 of hospitalization.

It is noteworthy that most participants colonized by Staphylococcus aureus were male, reported no sexual relations in the last 6 months, were using antibiotics, had no antiretroviral therapy prescribed and were submitted to an invasive procedure during hospitalization.

References

  • 1
    Anstead GM, Cadena J, Javeri H. Treatment of infections due to resistant Staphylococcus aureus. Methods Mol Biol. 2014;1085:259-309.
  • 2
    Van HSJ, Jensen SO, Vaska VL, Espedido BA, Paterson DL, Gosbell IB. Predictors of mortality in Staphylococcus aureus Bacteremia. Clin Microbiol Rev. 2012;25(2):362-86.
  • 3
    Weintrob A, Bebu I, Agan B, Diem A, Johnson E, Lalani T, et al. Randomized, double-blind, placebo-controlled study on decolonization procedures for Methicillin-Resistant Staphylococcus aureus (MRSA) among HIV-infected adults. PLoS One. 2015;10(5):e0128071.
  • 4
    Lambert ML, Suetens C, Savey A, Palomar M, Hiesmayr M, Morales I, et al. Clinical outcomes of health-care-associated infections and antimicrobial resistance in patients admitted to European intensive-care units: a cohort study. Lancet Infect Dis. 2011; 11(1):30-8.
  • 5
    Reinato LAF, Pio DPM, Lopes LP, Pereira FMV, Lopes AER, Gir E. Nasal colonization with Staphylococcus aureus in individuals with HIV/AIDS attended in a Brazilian Teaching Hospital. Rev Latino Am Enfermagem. 2013;21(6):1235-9.
  • 6
    Kotpal R, Krishna PS, Bhalla P, Dewan R, Kaur R. Incidence and risk factors of nasal carriage of Staphylococcus aureus in HIV-infected individuals in comparison to HIV-uninfected individuals: a case-control study. J Int Assoc Provid AIDS Care. 2016;15(2):141-7.
  • 7
    Oliva A, Lichtner M, Mascellino MT, Iannetta M, Ialungo AM, Tadadjeu Mewamba S, et al. Study of methicillin-resistant Staphylococcus aureus (MRSA) carriage in a population of HIV-negative migrants and HIV-infected patients attending an outpatient clinic in Rome. Ann Ig. 2013;25(2)99-107.
  • 8
    Lee LK, Win MK, Veeraraghavan MA, Wong CS, Chow AL, Leo YS. Short communication: risk factors for methicillin-resistant Staphylococcus aureus colonization among HIV patients at hospital admission. AIDS Res Hum Retroviruses. 2013;29(5):796-8.
  • 9
    Crum-Cianflone NF, Grandits G, Echols S, Ganesan A, Landrum M, Weintrob A, et al. Trends and causes of hospitalizations among HIV-infected persons during the late HAART era: what is the impact of CD4 counts and HAART use? J Acquir Immune Defic Syndr. 2010;54(3):248-57.
  • 10
    Creamer E, Dolan A, Sherlock O, Thomas T, Walsh J, Moore J, et al. The effect of rapidscreening for methicillin-resistant Staphylococcusaureus (MRSA) on the identification and earlier isolation of MRSA-positive patients. Infect Control Hosp Epidemiol. 2010;31(4):374-81.
  • 11
    Imaz A, Camoez M, Di Yacovo S, Gasch O, Dominguez MA, Vila A, et al. Prevalence of methicillin-resistant Staphylococcus aureus colonization in HIV-infected patients in Barcelona, Spain: a cross-sectional study. BMC Infect Dis. 2015; 15:243.
  • 12
    Vyas KJ, Shadyab AH, Lin CD, Crum-Cianflone NF. Trends and factors associated with initial and recurrent methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections among HIV-infected persons: an 18-year study. J Int Assoc Provid AIDS Care. 2014;13(3):206-13.
  • 13
    Lim CJ, Cheng AC, Kennon J, Spelman D, Hale D, Melican G, Sidjabat HE, Paterson DL, Kong DC, Peleg AY. Prevalence of multidrug-resistant organisms and risk factors for carriage in long-term care facilities: a nested case-control study. J Antimicrob Chemother. 2014;69(7):1972-80.
  • 14
    Blatt CR, Citadin CB, Souza FG, Mello RS, Galato D. Avaliação da adesão aos anti-retrovirais em um município no Sul do Brasil. Rev Soc Bras Med Trop [Internet]. 2009 [citado 2016 fev. 05];42(2):131-6. Disponível em: Disponível em: http://www.scielo.br/pdf/rsbmt/v42n2/v42n2a07.pdf
    » http://www.scielo.br/pdf/rsbmt/v42n2/v42n2a07.pdf
  • 15
    Silva ACO, Reis RK, Nogueira JA, Gir E. Quality of life, clinical characteristics and treatment adherence of people living with HIV/AIDS. Rev Latino Am Enferm. 2014; 22(6):994-1000.
  • 16
    Farley JE, Hayat MJ, Sacamano PL, Ross T, Carroll K. Prevalence and risk factors for methicillin-resistant Staphylococcus aureus in an HIV-positive cohort. Am J Infect Control. 2015;43(4):329-35.

Publication Dates

  • Publication in this collection
    Jul-Aug 2016

History

  • Received
    08 Mar 2016
  • Accepted
    28 June 2016
Universidade de São Paulo, Escola de Enfermagem Av. Dr. Enéas de Carvalho Aguiar, 419 , 05403-000 São Paulo - SP/ Brasil, Tel./Fax: (55 11) 3061-7553, - São Paulo - SP - Brazil
E-mail: reeusp@usp.br