Tratamiento antibiótico empírico inicial prolongado y riesgo de morbimortalidad en recién nacidos de muy bajo peso al nacer / Prolonged initial empirical antibiotic treatment and the risk of morbidity and mortality in very low birthweight infants

Resumen: Introducción: El objetivo de este estudio es evaluar la asociación entre la duración del tratamien to antibiótico empírico inicial y el desarrollo posterior de sepsis tardía, enterocolitis necrotizante (NEC) y muerte en recién nacidos de muy bajo peso al nacer (RNMBP). Pacientes y Método: Estudio cuantitativo, transversal analítico, en RNMBP ingresados a UCI neonatal durante un período de 5 años. Se consideró antibioterapia empírica inicial aquella que comenzó desde el nacimiento, sin conocer resultado de hemocultivos. Antibioterapia prolongada se estimó cuando la duración del tratamiento fue > 5 días. Se analizaron variables perinatales, e incidencia de sepsis tardía, NEC confirmada y mortalidad. Resultados: Se estudiaron un total de 266 RNMBP, con edad gestacional y peso de nacimiento promedios de 28,8 ± 2,5 semanas y 1.127 ± 264 g respec tivamente. Recibieron antibioterapia empírica inicial 213 (80,0%), siendo ésta prolongada en el 67,6%. Todos recibieron antibioterapia biasociada. Se pesquisaron 136 episodios de sepsis tardía, siendo los gérmenes más frecuentes el Staphylococcus coagulasa negativo y el Staphylococcus au reus. Del total de RN con antibioterapia empírica prolongada, hubo 20 casos de NEC confirmada y 15 fallecidos (10,4%) en el grupo analizado. Al comparar el uso de antibioterapia > 5 días ver sus tratamiento menor de 5 días, se observó una asociación estadísticamente significativa entre la antibioterapia prolongada y sepsis tardía (p = 0,03) y además de NEC confirmada (p = 0,03), pero no de mortalidad (p = 0,12). Conclusión: El uso de antibioterapia empírica inicial por 5 días o más se asoció a un riesgo aumentado de sepsis tardía y de NEC, pero no de la mortalidad en RNMBPN.

Abstract: Introduction: The objective of this study is to evaluate the association between the duration of ini tial empirical antibiotic treatment and the subsequent development of late-onset sepsis, necrotizing enterocolitis (NEC) and death in very low birth weight (VLBW) infants. Patients and Methods: Quantitative, cross-sectional, analytical study of VLBW infants admitted to the neonatal ICU were included over a period of five years. Initial empirical antibiotic therapy was that which started im mediately after birth, without knowing the results of blood cultures. It was considered prolonged antibiotic therapy when the treatment duration was > 5 days. Perinatal variables, as well as the inci dence of late-onset sepsis, confirmed NEC and mortality were analyzed. Results: 266 VLBW infants were studied, with an average gestational age and birth weight of 28.8 ± 2.5 weeks and 1.127 ± 264 g respectively. 213 infants received initial empiric antibiotic therapy (80.0%), which was prolonged in 67.6% of cases. All infants received two different antibiotics. 136 episodes of late-onset sepsis were described. The most common pathogens were coagulase-negative Staphylococcus and Staphylococcus aureus. Among the newborns with prolonged antibiotic therapy, there were 20 cases of confirmed NEC and 15 of the studied infants died (10.4%). When comparing the use of antibiotic therapy during > 5 days versus treatment less than 5 days duration, a statistically significant association was observed between prolonged antibiotic therapy and late-onset sepsis (p = 0.03) and confirmed NEC (p = 0.03), but not of mortality (p = 0.12). Conclusion: The use of empirical antibiotic therapy for five days or more was associated with an increased risk of late-onset sepsis and NEC, but not of mortality in VLBW infants.

Infecciones por Staphylococcus aureus meticilino resistente adquirido en la comunidad: hospitalización y riesgo de letalidad en 10 centros pediátricos de Argentina / Community-acquired methicillin-resistant Staphylococcus aureus infections: hospitalization and case fatality risk in 10 pediatric facilities in Argentina

Introducción. Las infecciones por Staphylococcus aureusmeticilino resistente adquirido en la comunidad (SAMR-C) son prevalentes en Argentina y el mundo; pueden tener evolución grave. Objetivos: Estimar tasa de hospitalización y factores de riesgo de letalidad de la infección por SAMR-C. Métodos. Estudio analítico transversal. Se incluyeron todos los pacientes < 15 años con infección por Staphylococcus aureusadquirido en la comunidad (SA-C) hospitalizados en 10 centros pediátricos, entre enero/2012-diciembre/2014. Resultados. Del total de 1141 pacientes con infección por SA-C, 904 (79,2%) fueron SAMR-C. La tasa de hospitalización de casos de SAMR-C (por 10 000 egresos) en < 5 años fue 27,6 en 2012, 35,2 en 2013 y 42,7 en 2014 (p= 0,0002). El grupo de 2-4 años fue el más afectado: 32,2, 49,4 y 54,4, respectivamente (p= 0,0057). Las presentaciones clínicas fueron infección de piel y partes blandas (IPPB): 66,2%; neumonía:11,5%; sepsis/bacteriemia: 8,5%; osteomielitis: 5,5%; artritis: 5,2%; absceso de psoas: 1,0%; pericarditis/endocarditis: 0,8%; meningitis: 0,6%; otras: 0,7%. La resistencia antibiótica fue, para eritromicina, 11,1%; clindamicina, 11,0%; gentamicina, 8,4%; trimetoprima-sulfametoxazol: 0,6%. Todas las cepas fueron sensibles a vancomicina. La letalidad fue 2,2% y los factores de riesgo asociados fueron --#91;OR (IC 95%)--#93; edad > 8 años (2,78; 1,05-7,37), neumonía (6,37; 2,37-17,09), meningitis (19,53; 2,40-127,87) y sepsis/bacteriemia (39,65; 11,94-145,55). Conclusiones. La tasa de infección por SAMR-C fue alta; la tasa de hospitalización aumentó en 2013-14; el grupo de 2-4 años fue el más afectado. Presentaron mayor riesgo de letalidad los > 8 años y las clínicas de neumonía, meningitis y sepsis.

Introduction. Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are prevalent both in Argentina and worldwide, and they may have a severe clinical course. Objectives: To estimate the hospitalization rate and case fatality risk factors of CA-MRSA infection. Methods. Cross-sectional, analytical study. All patients < 15 years old with community-acquired Staphylococcus aureus (CA-SA) infections admitted to 10 pediatric facilities between January 2012 and December 2014 were included. Results. Out of 1141 patients with CA-SA, 904 (79.2%) had CA-MRSA. The rate of hospitalization of CA-MRSA cases (per 10 000 discharges) among patients < 5 years old was 27.6 in 2012, 35.2 in 2013, and 42.7 in 2014 (p = 0.0002). The 2-4-year-old group was the most affected one: 32.2, 49.4, and 54.4, respectively (p = 0.0057). The clinical presentations included skin and soft tissue infections: 66.2%, pneumonia: 11.5%, sepsis/bacteremia: 8.5%, osteomyelitis: 5.5%, arthritis: 5.2%, psoas abscess: 1.0%, pericarditis/endocarditis: 0.8%, meningitis: 0.6%, and other: 0.7%. In terms of antibiotic resistance, 11.1% had resistance to erythromycin; 8.4%, to gentamicin; and 0.6%, to trimethoprim-sulfamethoxazole. All strains were susceptible to vancomycin. The case fatality rate was 2.2% and associated risk factors were (odds ratio --#91;95% confidence interval--#93;) age > 8 years (2.78, 1.05-7.37), pneumonia (6.37, 2.3717.09), meningitis (19.53, 2.40-127.87), and sepsis/bacteremia (39.65, 11.94-145.55). Conclusions. The rate of CA-MRSA infection was high; the rate of hospitalization increased in the 2013-2014 period; the 2-4-year-old group was the most affected one. A higher case fatality risk was observed among patients > 8 years old and those with the clinical presentations of pneumonia, meningitis, and sepsis.

Empirical antimicrobial therapy for late-onset sepsis in a neonatal unit with high prevalence of coagulase-negative Staphylococcus / Terapia antimicrobiana empírica para sepse tardia na unidade neonatal com alta prevalência de Staphylococcus coagulase negativo

Abstract Objective: The aim of this study was to compare two different empiric treatments for late-onset neonatal sepsis, vancomycin and oxacillin, in a neonatal intensive care unit with a high prevalence of coagulase-negative Staphylococcus. Methods: A cross-sectional study was conducted in an neonatal intensive care unit from 2011 to 2014. Data from the medical records of at-risk newborns were collected daily. Infections were defined according to the National Health Surveillance Agency criteria. Data analysis was performed using an internal program. Results: There was a significant reduction in the number of Staphylococcus aureus infections (p = 0.008), without endocarditis, meningitis, or lower respiratory tract infection, as well as a reduction in the frequency of deaths related to S. aureus infection. There were no significant changes in the incidence of Gram-negative bacterial or fungal infections. An increase in coagulase-negative Staphylococcus infections was observed (p = 0.022). However, there was no measured increase in related morbidity and mortality. There was a reduction in the median number of days of treatment with oxacillin from 11.5 to 6 days (p < 0.001) and an increase of one day in the median number of days of treatment with vancomycin (p = 0.046). Conclusions: Modification of the empiric treatment regimen for neonatal late-onset sepsis with use of oxacillin showed a significant reduction in S. aureus infections, as well as a reduction in the frequency of infections with major organ system involvement and mortality due to infection with this microorganism. As a result, oxacillin can be considered as an effective treatment for late-onset sepsis, making it possible to avoid broad-spectrum antibiotics.

Resumo Objetivo Comparar dois períodos com diferentes esquemas empíricos para tratamento de sepse neonatal tardia, incluindo vancomicina ou oxacilina respectivamente, em unidade neonatal de referência com alta prevalência de Staphylococcus coagulase negativo. Métodos Estudo transversal, feito em unidade neonatal de referência, de 2011 a 2014. Os dados foram coletados diariamente por vigilância ativa em prontuário de recém-nascidos de risco. As infecções foram notificadas conforme critérios definidos pela Agência Nacional de Vigilância Sanitária. O banco de dados e a análise foram feitos em programa interno. Resultados Ocorreu redução significativa da notificação de infecções por Staphylococcus aureus (p = 0,008), sem notificações de endocardite, meningite e infecções de vias aéreas inferiores, além de redução na frequência de óbitos pelo microrganismo e sem alteração significativa nas incidências de infecções por bactérias Gram negativas e fungos. Houve aumento de infecções S. aureus coagulase negativo (p = 0,022), mas sem aumento de morbidade e mortalidade. Ocorreu redução na mediana do tempo de uso de oxacilina, de 11,5 para 6 dias (p < 0,001), com aumento de mediana de um dia de uso de vancomicina (p = 0,046). Conclusões A modificação do esquema empírico com uso de oxacilina revelou redução significativa das infecções por S. aureus, além da redução na frequência de infecção de foco profundo e mortalidade pelo microrganismo. Considera-se que oxacilina pode ser usada como esquema de tratamento de sepse neonatal tardia para se evitar o uso de antibióticos de largo espectro.

The accessory gene regulator (agr) controls Staphylococcus aureus virulence in a murine intracranial abscesses model

Background: Intracranial abscesses are associated with high mortality. Staphylococcus aureus is one of the main pathogens that cause intracranial infection. Until now, there is no report to identify the key effectors of S. aureus during the intracranial infection. Methods: The murine intracranial abscesses model induced by S. aureus was constructed. The vital sign and survival rate of mice were observed to evaluate the infection. Histological examination was used to diagnose the pathological alterations of mouse tissues. The sensitivity of S. aureus to whole blood was evaluated by whole-blood killing assay. Results: In murine intracranial abscesses model, it was shown that the mortality caused by the accessory gene regulator (agr) locus deficient strain was significant decreased compared with its parent strain. Moreover, we found that RNAIII, the effector of agr system, was essential for the intracranial infection caused by S. aureus. In the further investigation, it was shown that restoration the expression of α-toxin in agr deficient strain could partially recover the mortality in the murine intracranial abscesses model. Conclusion: Our data suggested that the agr system of S. aureus is an important virulence determinant in the induction and mortality of intracranial abscesses in mice. .

Active surveillance to determine the impact of methicillin resistance on mortality in patients with bacteremia and influences of the use of antibiotics on the development of MRSA infection

Introduction Methicillin-resistant Staphylococcus aureus (MRSA) is among the most important pathogens of nosocomial infections, mainly in intensive care units (ICUs), and accounts for 40-60% of all healthcare-associated S. aureus infections. We evaluated the incidence of nosocomial infection by S. aureus, identified the risk factors for MRSA infection, and evaluated the effect of resistance to methicillin on mortality in patients. Methods We conducted MRSA surveillance at a university hospital in Brazil from January 1, 2010, to December 31, 2010, and performed a retrospective case-control matched study to evaluate the frequency of subsequent MRSA bacteremia and death among patients. We evaluated and compared the risk factors between patients with MRSA and methicillin-sensitive Staphylococcus aureus (MSSA) infection. Results Sepsis was the most common cause of infection (17.7/1,000 patient-days), followed by surgical site (11.4/1,000 patient-days), pneumonia (4.1/1,000 patient-days), and urinary tract infection (2.4/1,000 patient-days). The significant risk factors were time of hospitalization, use of central vascular catheter (CVC), urinary catheter, nasogastric tube, parenteral nutrition, tracheostomy, mechanical ventilation, and previous antibiotic administration, the latter of which was the only independent risk factor for MRSA infection. Mortality was significantly higher in patients with MRSA. The number of antibiotics tested was not related to increases in the frequency of MRSA/1,000 patient-days. The incidence of mortality attributable to MRSA (bloodstream infection) BSI was 50%. Conclusions Surveillance results showed that the use of high levels of antibiotics was directly related to the development of MRSA infection, and the mortality attributable to MRSA in patients with bacteremia was significant. .

Fatores de risco e letalidade de infecção da corrente sanguínea laboratorialmente confirmada, causada por patógenos não contaminantes da pele em recém-nascidos / Risk factors and lethality of laboratory-confirmed bloodstream infection caused by non-skin contaminant pathogens in neonates

OBJECTIVE: To evaluate risk factors and lethality of late onset laboratory-confirmed bloodstream infection (ICSLC) in a Brazilian neonatal unit for progressive care (NUPC). Methods: This was a case-control study, performed from 2008 to 2012. Cases were defined as all newborns with late onset ICSLC, excluding patients with isolated common skin contaminants. Controls were newborns who showed no evidence of late onset ICSLC, matched by weight and time of permanence in the NUPC. Variables were obtained in the Hospital Infection Control Committee (HICC) database. Analysis was performed using the Statistical Package for the Social Sciences (SPSS). The chi-squared test was used, and statistical significance was defined as p < 0.05, followed by multivariate analysis. RESULTS: 50 patients with late onset ICSLC were matched with 100 patients without late onset ICSLC. In the group of patients with late onset ICSLC, a a significant higher proportion of patients who underwent surgical procedures (p = 0.001) and who used central venous catheter (CVC) (p = 0.012) and mechanical ventilation (p = 0.001) was identified. In multivariate analysis, previous surgery and the use of CVC remained significantly associated with infection (p = 0.006 and p = 0.047; OR: 4.47 and 8.99, respectively). Enterobacteriacea was identified in 14 cases, with three (21.4%) deaths, and Staphylococcus aureus was identified in 20 cases, with three (15%) deaths. CONCLUSIONS: Surgical procedures and CVC usage were significant risk factors for ICSLC. Therefore, prevention practices for safe surgery and CVC insertion and manipulation are essential to reduce these infections, in addition to training and continuing education to surgical and assistance teams.

OBJETIVO: Avaliar os fatores de risco e a letalidade da infecção da corrente sanguínea laboratorialmente confirmada (ICSLC) de início tardio em uma Unidade Neonatal de Cuidados Progressivos (UNCP) brasileira. MÉTODOS: Trata-se de um estudo caso-controle realizado de 2008 a 2012. Os casos foram definidos como todos os recém-nascidos com ICSLC de início tardio, excluindo pacientes isolados com contaminantes da pele comuns. Os controles foram recém-nascidos que não mostraram qualquer evidência de ICSLC de início tardio, sendo separados por peso e tempo de permanência na UNCP. As variáveis foram obtidas na base de dados da Comissão de Controle de Infecção Hospitalar (CCIH). A análise foi realizada utilizando o Pacote Estatístico para Ciências Sociais. O teste χ² foi utilizado e a relevância estatística foi definida como p < 0,05, seguida pela análise multivariada. RESULTADOS: No estudo, 50 pacientes com ICSLC de início tardio foram combinados com 100 pacientes sem ICSLC de início tardio. No grupo de pacientes com ICSLC de início tardio, identificamos uma proporção significativamente maior de pacientes que foram submetidos a procedimentos cirúrgicos (p = 0,001) e que usaram cateter venoso central (CVC) (p = 0,012) e ventilação mecânica (p = 0,001). Na análise multivariada, cirurgia prévia e uso de CVC permaneceram significativamente associados à infecção (p = 0,006 e p = 0,047; OU: 4,47 e 8,99, respectivamente). A Enterobacteriacea foi identificada em 14 casos, com três (21,4%) óbitos, e Staphylococcus aureus foi identificado em 20 casos, com três (15%) óbitos. CONCLUSÕES: Procedimentos cirúrgicos e uso de CVC constituíram fatores de risco significativos para ICSLC. Portanto, práticas de prevenção para cirurgia segura, inserção e manipulação de CVC são essenciais para reduzir essas infecções, além de treinamento e educação contínua às equipes cirúrgicas e de assistência.

Healthcare-associated Staphylococcus aureus bloodstream infection: length of stay, attributable mortality, and additional direct costs

This study aimed to determine the excess length of stay, extra expenditures, and attributable mortality to healthcare-associated S. aureus bloodstream infection (BSI) at a teaching hospital in central Brazil. The study design was a matched (1:1) case-control. Cases were defined as patients > 13 years old, with a healthcare-associated S. aureus BSI. Controls included patients without an S. aureus BSI, who were matched to cases by gender, age (± 7 years), morbidity, and underlying disease. Data were collected from medical records and from the Brazilian National Hospital Information System (Sistema de Informações Hospitalares do Sistema Único de Saúde - SIH/SUS). A Wilcoxon rank sum test was performed to compare length of stay and costs between cases and controls. Differences in mortality between cases and controls were compared using McNemar's tests. The Mantel-Haenzel stratified analysis was performed to compare invasive device utilization. Data analyses were conducted using Epi Info 6.0 and Statistical Package for Social Sciences (SPSS 13.0). 84 case-control pairs matched by gender, age, admission period, morbidity, and underlying disease were analyzed. The mean lengths of hospital stay were 48.3 and 16.2 days for cases and controls, respectively (p < 0.01), yielding an excess hospital stay among cases of 32.1 days. the excess mortality among cases compared to controls that was attributable to s. aureus bloodstream infection was 45.2%. Cases had a higher risk of dying compared to controls (OR 7.3, 95% CI 3.1-21.1). Overall costs of hospitalization (SIH/SUS) reached US$ 123,065 for cases versus US$ 40,247 for controls (p < 0.01). the cost of antimicrobial therapy was 6.7 fold higher for cases compared to controls. healthcare-associated s. aureus BSI was associated with statistically significant increases in length of hospitalization, attributable mortality, and economic burden. Implementation of measures to minimize the risk of healthcare-associated bacterial infections is essential.

Mortality among critically ill patients with methicillin-resistant Staphylococcus aureus bacteremia: a multicenter cohort study in Colombia / Mortalidad en pacientes gravemente enfermos con bacteriemia por Staphylococcus aureus resistente a la meticilina:un estudio multicéntrico de cohortes en Colombia

Objetivo. Evaluar los factores de riesgo asociados con la aparición de bacteriemia por Staphylococcus aureus resistente a la meticilina (MRSA), su pronóstico y los factores determinantes de la mortalidad en pacientes gravemente enfermos en Colombia. Métodos. Estudio retrospectivo multicéntrico de cohortes realizado en el período del 2005 al 2008 en 16 instituciones de atención de salud de referencia públicas y privadas de Bogotá, Colombia, que forman parte de una red nacional de vigilancia epidemiológica y de una red hospitalaria de 4 469 camas. Se analizaron la aparición de resistencia a la meticilina y la mortalidad mediante análisis descriptivos y de tiempo transcurrido hasta un suceso; se estableció un modelo multifactorial de regresión de riesgos proporcionales de Cox para evaluar la asociación entre la resistencia a la meticilina y la mortalidad. Resultados. Se estudiaron 372 pacientes: 186 con bacteriemia por MRSA, apareados aleatoriamente con 186 con bacteriemia por Staphylococcus aureus sensible a la meticilina (MSSA). La cirugía previa, el tratamiento con antibióticos y las infecciones intrahospitalarias se asociaron independientemente con la resistencia a la meticilina. El MRSA provocó hospitalizaciones más prolongadas en los sobrevivientes (mediana de 24 frente a 18 días, P = 0,014). Los factores predictivos de mortalidad fueron: la edad del paciente, un nivel de creatinina superior a 1,21 mg/dl al ingresar en la UCI, la septicemia grave y el requerimiento de inotrópicos. El tratamiento antimicrobiano apropiado y el cambio de tratamiento antimicrobiano constituyeron factores protectores independientes, igual que el sexo masculino. Conclusiones. La resistencia a la meticilina per se no fue un factor pronóstico independiente de la mortalidad. Las condiciones previas, como la edad, la insuficiencia renal inicial, la septicemia grave y el requerimiento de inotrópicos explicaron la mortalidad observada. El tratamiento antimicrobiano apropiado seguía siendo un factor protector. Es obligatorio hacer un llamamiento para mejorar las medidas de control de las infecciones en Colombia y en otros contextos similares.

Objective. To evaluate risk factors associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia emergence, its prognosis, and mortality-determining factors in critically ill patients in Colombia. Methods. A multicenter, retrospective cohort study conducted in 2005–2008 at 16 public and private reference health care institutions in Bogotá, Colombia, that form part of a national epidemiological surveillance network and a hospital network with 4 469 beds. Methicillinresistant emergence and mortality were analyzed using descriptive and time-to-event analysis; a multivariate Cox proportional hazard regression model was built to test the association between methicillin resistance and mortality. Results. A total of 372 patients were studied: 186 with MRSA bacteremia, randomly matched with 186 with methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia. Previous surgery, antibiotic exposure, and hospital-acquired infections were independently associated with methicillin resistance. MRSA caused longer hospital stays among survivors (median 24 versus 18 days, P = 0.014). Mortality predictors were: patient age, creatinine level over 1.21mg/dl at ICU admission, severe sepsis, and inotropic requirement. Appropriate antimicrobial therapy and antimicrobial therapy change were independent protective factors, as was male gender. Conclusions. Methicillin resistance per se was not a mortality-independent prognostic factor. Previous conditions, such as age, baseline renal impairment, severe sepsis, and inotropy demand explained the observed mortality. Appropriate antimicrobial therapy remained a protective factor. A call to improve infection control measures in Colombia is mandatory.

Methicillin-resistant Staphylococcus aureus bloodstream infection: risk factors and clinical outcome in non-intensive-care units / Infecção de corrente sanguínea por Staphylococcus aureus resistente à meticilina: fatores de risco e evolução clínica em unidades não críticas

INTRODUCTION: Methicillin-resistant Staphylococcus aureus (MRSA) is spread out in hospitals across different regions of the world and is regarded as the major agent of nosocomial infections, causing infections such as skin and soft tissue pneumonia and sepsis. The aim of this study was to identify risk factors for methicillin-resistance in Staphylococcus aureus bloodstream infection (BSI) and the predictive factors for death. METHODS: A retrospective cohort of fifty-one patients presenting bacteraemia due to S. aureus between September 2006 and September 2008 was analysed. Staphylococcu aureus samples were obtained from blood cultures performed by clinical hospital microbiology laboratory from the Uberlândia Federal University. Methicillinresistance was determined by growth on oxacillin screen agar and antimicrobial susceptibility by means of the disk diffusion method. RESULTS: We found similar numbers of MRSA (56.8%) and methicillin-susceptible Staphylococcus aureus (MSSA) (43.2%) infections, and the overall hospital mortality ratio was 47%, predominantly in MRSA group (70.8% vs. 29.2%) (p=0.05). Age (p=0.02) was significantly higher in MRSA patients as also was the use of central venous catheter (p=0.02). The use of two or more antimicrobial agents (p=0.03) and the length of hospital stay prior to bacteraemia superior to seven days (p=0.006) were associated with mortality. High odds ratio value was observed in cardiopathy as comorbidity. CONCLUSIONS: Despite several risk factors associated with MRSA and MSSA infection, the use of two or more antimicrobial agents was the unique independent variable associated with mortality.

INTRODUÇÃO: Methicillin-resistant Staphylococcus aureus (MRSA), se disseminou nos hospitais em diferentes regiões do globo, e é atualmente o principal agente de infecções hospitalares causando infecções de pele, tecidos moles, pneumonia e sepse. O objetivo deste estudo foi identificar fatores de risco para resistência à meticilina em infecções de corrente sanguínea por Staphylococcus aureus e fatores preditivos de mortalidade. MÉTODOS: Uma coorte de 51 pacientes apresentando bacteremia por S. aureus, entre setembro de 2006 a setembro de 2008 foi analisada. Amostras de S. aureus foram obtidas a partir de hemoculturas realizadas pelo laboratório de microbiologia do hospital de clínicas da Universidade Federal de Uberlândia. A resistência à meticilina foi determinada pelo crescimento no agar triagem para oxacilina e a sensibilidade aos antimicrobianos pelo método de difusão em agar. RESULTADOS: Infecções por MRSA (56,8%) e methicillin-susceptible Staphylococcus aureus (MSSA) (43,2%) foram similares e a taxa de mortalidade hospitalar foi de 47%, predominantemente no grupo infectado por MRSA (70,8% vs. 29,2%) (p=0,05). Idade (p=0,02) e a presença de cateter vascular central (p=0,02) foram significantes no grupo de infectados por MRSA. A evolução demonstrou que o uso de dois ou mais agentes antimicrobianos (p=0,03) e tempo de internação prévio à bacteremia superior a sete dias (p=0,006) foram associados à morte. Altos valores de odds ratio foram observados para cardiopatia como comorbidade. CONCLUSÕES: Embora vários fatores de risco tenham sido associados a infecções por MRSA e MSSA e mortalidade o uso de dois ou mais agentes antimicrobianos foi a única variável independente para mortalidade.

Intravenous device associated blood stream staphylococcal infection in paediatric patients.

Background & objectives: Intravenous device (IVD) associated nosocomial blood stream infections due to staphylococci are major cause of morbidity and mortality. The present study was carried out to assess the frequency of staphylococcal IVD associated infections in a paediatric ward of a tertiary case hospital. Prevalence of resistance to commonly used antimicrobials in hospital acquired staphylococcal isolates was also tested. Methods: Children admitted in paediatric wards with IVD for more than 48 h were enrolled. Blood, IVD tip at the time of removal, skin swab at the site of insertion of IVD and nasal swab were collected and cultured by standard protocol. All staphylococcal isolates from any source were analyzed for antimicrobial susceptibility by disk diffusion method. Genotyping matching of those staphylococcal isolates was done which were isolated from different sites of the same patient, but were phonotypically similar. Genotype of blood isolate was compared with genotype of isolate from nose/IVD/skin. Results: Staphylococcus aureus was the most frequent blood isolate (8.7%) followed by Candida (2.9%), coagulase negative staphylococci (CoNS 2.6%), Pseudomonas spp. (0.4%), Klebsiella spp. (0.3%) and Escherichia coli (0.1%). Isolation of microorganisms from blood was significantly higher in patients whose skin, IVD and nose were colonized by same microorganism (P<0.001). None of the staphylococcal isolate was found to be resistant to glycopeptides (vancomycin and teicoplanin). High penicillin and oxacillin resistance was present in both S. aureus (penicillin resistance; 76.8%, oxacillin resistance; 66.7%) and CoNS (penicillin resistance; 73.3%, oxacillin resistance; 60.0%). Among CoNS biotypes, S. haemolyticus was commonest blood isolate while S. epidermidis was commonest isolate from Skin/nose. Only 33.3 per cent of S. aureus blood stream infections and most of S. epidermidis and S. haemolyticus blood infections were IVD associated. Interpretation & conclusions: Staphylococci were the major causative agent of nosocomial blood stream infections. All episodes of septicaemia due to S. epidermidis and S. haemolyticus were IVD associated while only 1/3 of S. aureus septicaemia was IVD associated.

Impacto de la resistencia a la meticilina sobre la mortalidad y vigilancia de la sensibilidad a la vancomicina en bacteriemias causadas por Staphylococcus aureus / Impact of methicillin resistance on mortality and surveillance of vancomycin susceptibility in bacteremias caused by Staphylococcus aureus

Staphylococcus aureus es uno de los principales patógenos nosocomiales y produce una alta morbimortalidad en numerosos hospitales del mundo. Además, la incidencia de bacteriemias por este microorganismo ha aumentado significativamente en las últimas décadas. Los objetivos del presente trabajo fueron identificar los factores de riesgo que favorecen la aparición de resistencia a la meticilina en aislamientos de S. aureus y los factores que afectan la mortalidad por bacteriemias asociadas a este patógeno, así como evaluar la sensibilidad a la vancomicina de las cepas resistentes a la meticilina. Se estudiaron 39 aislamientos de S. aureus provenientes de hemocultivos de pacientes internados con bacteriemia en la Nueva Clínica Chacabuco de Tandil (Pcia. de Buenos Aires, Argentina) en el período 01/2006-12/2008. La mortalidad global fue del 51,3% y estuvo significativamente asociada con la resistencia a la meticilina (OR: 4,20; IC95%: 1,08-16,32; p: 0,05); aunque dicho factor no fue un predictor independiente de mortalidad. La cirugía previa (OR: 17,23; IC95%: 1,80-164,60) y la estancia previa en la unidad de cuidados intensivos (OR: 21,12; IC95%: 2,33-191,30) fueron predictores independientes de la resistencia a la meticilina y la asistencia respiratoria mecánica (OR: 15,99; IC: 3,24-78,86) fue un predictor independiente de la mortalidad. No se detectaron cepas con sensibilidad disminuida a la vancomicina. Todos los aislamientos estudiados fueron sensibles in vitro a la vancomicina, con una CIM50 y una CIM90 de 0,5 μg/ml.

Staphylococcus aureus is a major nosocomial pathogen that causes severe morbidity and mortality in many hospitals worldwide. Besides, the incidence of S. aureus bacteremia has significantly increased over the past decades. The aims of this study were to detect the risk factors for methicillin resistance and mortality and to evaluate vancomycin susceptibility in methicillin-resistant isolates. Thus, 39 S. aureus isolates from blood cultures of hospitalized patients with bacteremia were studied in Nueva Clínica Chacabuco Tandil, Buenos Aires, Argentina during 01/2006-12/2008. The overall mortality was 51.3%, which was significantly associated with methicillin resistance (OR: 4.20, IC95%: 1.08-16.32, p: 0.05), even though it was not an independent mortality predictor as it was the mechanical ventilation (OR: 15.99, IC95%: 3.24 - 78.86). Previous surgery (OR: 17.23, IC95%: 1.80-164.60) and hospitalization in intensive care units (OR: 21.12, IC95%: 2.33-191.30) were independent predictors of meticillin-resistance. No isolates were found with reduced vancomycin susceptibility. All the studied isolates were in vitro susceptible to vancomycin with a MIC50 and MIC90 of 0.5 μg/ml.

Inadequate timing between corticosteroid and antibiotics applications increases mortality due to sepsis

This study tested the hypothesis that the use of corticosteroids prior to antibiotics can lower the mortality rate in severe infections by S. aureus or Gram-negative bacilli, using an animal model. This study was a prospective and controlled study, placed in a university laboratory. Seven hundred and sixty mice distributed into three groups (Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae infected). The interventions in each group were: I) infection control (intra-peritoneal); II) treatment solely with antibiotics (teicoplanin or amikacin); III) antibiotics administered prior to the corticosteroid (methylprednisolone); IV) antibiotics administered after the corticosteroid. Mortality in the E. coli group, subgroup I: 100 percent; subgroup II: 55 percent (p<0.001); subgroup III: 62.5 percent (p=0.2488, compared to subgroup II); subgroup IV: 20 percent (p<0.01 compared to subgroups II and III). Mortality in the K. pneumoniae group: subgroup I: 100 percent; subgroup II: 72.5 percent (p<0.01); subgroup III: 80 percent (p=0.215 compared to subgroup II); subgroup IV: 45 percent (p<0.01 compared to subgroups II and III). Mortality in the S. aureus group: subgroup I: 82.5 percent; II: 42.5 percent (p<0.001); subgroup III: 77.5 percent (p=0.2877 compared to subgroup I); subgroup IV: 32.5 percent (p=0.1792 compared to subgroup II). The use of corticosteroids prior to antibiotics lowered the mortality rate caused by Gram-negative bacteria and did not affect the mortality caused by S. aureus. When used after starting treatment with antibiotics, the corticosteroid was not superior to the use of antibiotics alone in the case of the Gram-negative bacteria, and was not significantly different from non-treatment of the infection, in the case of S. aureus.

Staphylococcus aureus bacteremia: what is the impact of oxacillin resistance on mortality?

In order to analyse the impact of oxacillin resistance on the mortality of Staphylococcus aureus bacteremia, and to assess the antimicrobial susceptibility of community-acquired strains in two large university hospitals (the Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo and the Instituto Central do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo), we carried out a four-month-long prospective cohort study, which included 163 consecutive cases of S. aureus bacteremia. Of these, 140 (85.9 percent) were hospital-acquired, 9 (5.5 percent) were community-acquired and 14 (8.6 percent) were of indeterminate origin. No cases of community-acquired infection by oxacillin-resistant S. aureus was identified. Among hospital-acquired infections, oxacillin-resistant S. aureus was responsible for 64.3 percent of cases. Mortality up to 15 days after diagnosis of bacteremia was 27 percent (18/67) for infections caused by susceptible strains and 33 percent (32/96) for infections caused by oxacillin-resistant strains (p=0.10). The following independent risk factors for the acquisition of oxacillin-resistant S. aureus were identified in multiple logistical regression analysis: age over 60 years, use of corticoids; presence of a central vascular catheter, and previous use of antibiotics.

Significado de la fiebre persistente o recurrente durante el tratamiento de la endocarditis infecciosa / Clinical significance of persistent or recurrent fever during the treatment of infective endocarditis

Se evaluaron 81 pacientes con endocarditis infecciosa con el objeto de establecer la significación clínica de la presencia de fiebre persistente (FP) y/o fiebre ecurrente (FR) durante el tratamiento. Un total de 46 pacientes (56.8%) (Grupo 1) tuvieron FP y/o FR durante el tratamiento: 35 FP y 16 FR, que se compararon con 35 sin FP/FR (Grupo 2). No hubo diferencias en la edad, sexo, permanencia hospitalaria, origen nosocomial, demora diagnóstica y comorbilidad asociada. El compromiso aórtico (47.8 vs 34.2%) y tricuspídeo (21.7 vs 11.4%) y la infección por Staphylococcus aureus (55.5 vs 28%) fueron más frecuentes en el Grupo 1, aunque no significativamente. El S. aureus meticilino resistente (SAMR) (22.2 vs 4%), las complicaciones (95.6 vs 65.7%), la disfunción renal (58.6 vs 31.4%), el embolismo mayor (60.8 vs 34%), los fenómenos microvasculares (43.4 vs 17.1%) y la cirugía valvular (34.7 vs 11.4%) ocurrieron significativamente en el Grupo 1 (p<0.05). Se estableció una causa de FP en 32/35 pacientes: fenómenos microvasculares (14 pacientes), embolismo mayor (10), abscesos valvulares (5), bacteriemia persistente (4) y aneurismas micóticos (2). La flebitis de infusión (6/16pacientes), fiebre medicamentosa (3) e infección nosocomial (3) fueron las causas más comunes de FR. La mortalidad global fue del 39.5% y ocurrió en 52.2% del Grupo 1 y 22.9% del Grupo 2 (p=0.007) y en el grupo 1 seasoció a comorbilidad, embolismo mayor, sepsis severa, encefalopatía, insuficiencia cardíaca, infección por SAMRy antibioticoterapia inicial inapropiada (p<0.05). Se propone una metodología de evaluación en pacientes con esta problemática.

Staphylococcus aureus bacteremia: comparison of two periods and a predictive model of mortality

Staphylococcus aureus is an important pathogen causing bacteremia, primarily affecting hospitalized patients. We studied the epidemiology of S. aureus bacteremia, comparing two periods (early and mid 1990s) and developed a predictive model of mortality. A nested case-control was done. All 251 patients over 14 years old with positive blood cultures for S. aureus were selected. MRSA (methicillin resistant S. aureus) was isolated in 63 percent of the cases. When comparing the two periods MRSA community-acquired bacteremia increased from 4 percent to 16 percent (p=0.01). There was no significant difference in the mortality rate between the two periods (39 percent and 33 percent, p=0.40). Intravascular catheters provoked 24 percent of the cases of bacteremia and were associated with the lowest rate of mortality. In a logistic regression analysis, three variables were associated with death: septic shock, source of bacteraemia and resistance to methicillin. The probability of dying among patients with MRSA and those with methicillin sensitive S. aureus bacteraemia ranged from 10 percent to 90 percent and from 4 percent to 76 percent, respectively, depending on the source of the bacteraemia and the occurrence of septic shock. The MRSA found in Brazil may be a particularly virulent strain.

Sepsis estafilocócica / Staphylococcal sepsis

Con la finalidad de profundizar en el conocimiento de la sepsis por estafilococo aureus, se realizó un estudio retrospectivo de 51 pacientes, todos ingresados en el hospital "Pedro Soto Alba", en el período de enero 1989 hasta diciembre 1998; se precisó el aislamiento del germen en hemocultivo. Los datos que se obtuvieron mediante la revisión de las historias clínicas de los pacientes afectados por esta causa fueron: edad, sexo, valoración nutricional y condiciones favorecedoras de la sepsis. La edad menor de 1 año, el sexo masculino y los pacientes desnutridos favorecieron la sepsis. La fiebre, la toma del estado general y la hepatomegalia fueron las manifestaciones clínica más frecuentes. Se plantea que existe una alta mortalidad por sepsis estafilocócica y que ésta es más elevada cuando el diagnóstico se realiza tardíamente. Para esta investigación se tuvo el consentimiento informado de la institución(AU)

A retrospective study of 51 patients admitted to "Pedro Soto Alba" hospital from January 1989 to December 1998 was carried out to delve into sepsis caused by Staphylococcus aureus and for this end, isolation of germ in hemoculture was required. Data obtained from a review of the medical histories of the patients affected by this cause were: age, sex, nutritional assessment and sepsis favoring conditions. Under one-year old age, male sex and undernourished patients favored the occurrence of sepsis. Fever, affected general status and hepatomegalia were the most frequent clinical manifestations. It is stated that mortality rate from staphylococcal sepsis is high and that it is much higher if diagnosis is late. The institution gave its informed consent for the conduction of this research work(AU)

Endocarditis aguda estafilocóccica fatal con periodontitis servera / Staphylococcal acute endocarditis with severe periodontitis

La endocarditis infecciosa usualmente está asociada con una alteración del endocardio, la cual promueve los depósitos de fibrina donde las bacterias, en su mayoría Streptococcus spp., se establecen y de ahí se descargan a la sangre. El diagnóstico se hace empleando imágenes de ecocardiografía, realizando hemocultivos e investigando los síntomas clínicos. El presente caso corresponde a una niña de un año y nueve meses de edad, que desarrolló una endocarditis asociada con una infección por Staphylococcus aureus. La causa de muerte fue a un choque séptico con múltiples embolias sépticas en diversos órganos. La posible puerta de entrada la constituyó una sepsis oral con gingivitis sangrante y caries. Este caso indica que una higiene oral pobre representa un riesgo de invasión bacteriana con infección en tejidos cardiacos previamente normales. En nuestro país, frecuentemente hay casos de niños con lesiones orales como las observadas en el presente caso. Por esta razón, es importante una atención apropiada y el cuidado de estos pacientes. (Rev Cost Cienc Med 2000; 21(3-4): 171-7. Palabra clave: endocarditis aguda infecciosa, sepsis oral, periodontitis, ecocaridografía, Staphylococcus aureus.