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Direct-acting antivirals (DAAs) for HCV treatment have improved tolerance and efficacy among adults, but experience in vertical transmission is scarce. In our vertically HIV/HCV co-infected youth cohort of 58 patients, DAA achieved excellent rates of cure among naïve and pretreated individuals. Treating vertically infected seems important as 29.6% displayed advanced fibrosis at treatment initiation.

Introduction Pneumocystis jirovecii pneumonia (PJP) is a life-threatening condition in immunocompromised children. Our aim is to analyze the epidemiologic and clinical characteristics of PJP cases in our setting, describing the prognosis and related risk factors. Methods Retrospective study including all pediatric patients (≤18 years) with PJP admitted to our hospital (January 1989–December 2016). Case definition: patient with acute pneumonitis and P. jirovecii detection in bronchoalveolar lavage or tracheal aspirate using methenamine silver or direct antibody fluorescence staining, or Real-Time Polymerase Chain Reaction. Results Twenty-five cases (0.9 cases/year) were identified. Median age was 2.2 years (interquartile range: 0.5–12.3), 64% were male, and 12% were receiving appropriate antimicrobial prophylaxis. Cytomegalovirus coinfection was detected in 26% cases. The most common underlying diseases were primary immunodeficiencies (36%) and 16% were human immunodeficiency virus (HIV)-infected children. Eighteen were admitted to the pediatric intensive care unit (PICU) and overall 30-day mortality was 20% (31.25% in HIV non-infected vs 0% in HIV-infected patients; OR: 0.33, 95% CI: 0.02–7.24, p = 0.55). Clinical outcome was worse in girls and those patients requiring adjuvant steroid therapy. HIV non-infected patients, higher initial LDH, younger age and shorter time elapsed between diagnosis of PJP and the underlying disease were identified as risk factors to be admitted to the PICU (p = 0.05, p = 0.026, p = 0.04 and p = 0.001 respectively). Conclusion Accompanying the widespread use of combined antiretroviral therapy, PJP has been diagnosed almost exclusively in HIV non-infected children at our institution. Moreover, significant higher morbidity rates associated with PJP are seen in this group of patients.

What is known and objective Tocilizumab is an IL‐6 receptor inhibitor agent which has been proposed as a candidate to stop the inflammatory phase of infection by the severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2). However, safety data of tocilizumab in pregnant women and their newborn are scarce. We aimed to describe maternal and neonatal safety outcomes associated with tocilizumab treatment in pregnant women with severe COVID‐19. Methods This is a retrospective study of severe COVID‐19 pregnant women, treated with tocilizumab in two Spanish hospitals between 1 March and 31 April 2020. Demographics, medical history, clinical and radiologic findings, treatment information and laboratory data of mothers and their newborns were collected from electronic medical records. Results and discussion A total of 12 pregnant women were identified to have received tocilizumab during pregnancy in the two hospitals. Median gestational age at admission was 27.7 weeks (interquartile range, 18.0–36.4). Most of them received lopinavir/ritonavir, azithromycin and hydroxychloroquine, two patients received corticosteroids and one received interferon beta 1B. All 12 pregnancies resulted in live births. Somatometric values were normal for all newborns, and evolution at 14 and 28 days was favourable for all of them. Hepatotoxicity was observed in 2 patients, which improved or resolved at discharge. Cytomegalovirus reactivation was detected in another patient who had also received corticosteroids for 15 days, causing a congenital infection in her newborn. Both hepatotoxicity and viral reactivation adverse events were classified as possibly related to tocilizumab administration according to Naranjo's causality algorithm. What is new and conclusions It does not appear that tocilizumab has detrimental effects for the mother and newborn. Close monitoring of infections should be considered, especially if other immunosuppressive agents are used., Evolution of cytomegalovirus viral load and serology tests in one pregnant patient, in which viral reactivation was detected. She received a single dose of tocilizumab and methylprednisolone therapy for 15 days. Baseline IgM antibodies and amniotic fluid polymerase‐chain‐reaction were negative, but they became positive 6 days after tocilizumab infusion and viral load was detected on day 13.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations, Background The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. Methods Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. Discussion There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population, The study has been awarded with a Spanish Government grant (Instituto de Salud Carlos III: COV20/00188). It covers the expenses for transporting, processing and analyzing samples, database creation and maintenance, and hiring support staff

Objective This study aimed to evaluate the evidence of mother-to-child transmission of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Methods This is a descriptive, multicenter, observational study in nine tertiary care hospitals throughout Spain. The study population was women with COVID-19 during pregnancy. Mother-to-child transmission was defined as positive real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) of SARS-CoV-2 in amniotic fluid, cord blood, placenta or neonatal nasopharyngeal swabs taken immediately after birth. Results We included 43 singleton pregnant women and one twin pregnancy, thus we obtained 45 samples of placenta, amniotic fluid and umbilical cord blood. The median gestational age at diagnosis was 34.7 weeks (range 14 to 41.3). The median interval between positive RT-PCR and delivery was 21.5 days (range 0 to 141 days). Fourteen women (31.8%, 95%CI 18.6-47.6%) were positive at the time of delivery. There was one singleton pregnancy with SARS-CoV-2 RT-PCR positive in the placenta, amniotic fluid and umbilical cord blood (2.2%, 95%CI 0.1-11.8%). Nasopharyngeal aspiration was performed on 38 neonates at birth, all of which were negative (0%, 95%CI 0-9.3%). In 11 neonates the nasopharyngeal aspiration was repeated at 24-48 hours, and one returned positive (9.1%, 95%CI 0.2-41.3%). Conclusions The presence of the SARS-CoV-2 in placenta, amniotic fluid and cord blood shows that mother-to-child transmission is possible but uncommon.

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW, 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up, three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4&ndash, 6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4&ndash, 39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Part prematur Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Parto prematuro Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV; Premature delivery Coronavirus disease 2019 (COVID-19), which is caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a pandemic in January 2020. Although most of the cases in pregnant women are mild, there are reports of increasing severe infection in pregnancy. Only a few case of SARS-CoV-2 infection in preterm neonates delivered by mothers with COVID-19 have been reported till date. The possibility of in utero transmission of SARS-CoV-2 is highly controversial.1,2 While SARS-CoV-2 has been detected in several neonates by reverse transcriptionpolymerase chain reaction (RT-PCR) of nasopharyngeal swabs collected in the early hours or days of life,3,4 the reliability of these swabs is under scrutiny, as there is a chance of contamination by coronavirus-infected maternal body fluids.

National Network of HIV-infected Children (CORISPE); National Pediatric TB Network (pTBred) of Spain; Translational Research Network in Pediatric Infectious Diseases (RITIP)., [Background] Tuberculosis (TB) is the leading opportunistic infection in children with human immunodeficiency virus (HIV), but is uncommon in low prevalence regions. We aim to describe the changing epidemiology and clinical presentation of TB-HIV co-infection in a cohort of HIV-infected children in Spain., [Methods] Children diagnosed with TB between 1995 and 2016 in the paediatric HIV cohort were identified. The incidence and clinical presentation were compared in three periods: 1995–1999 (P1, before initiation of combined antiretroviral therapy, cART), 2000–2009 (P2, increase in immigration), and 2010–2016 (P3, decrease in immigration)., [Results] We included 29 TB cases among 1183 children aged 10 years (20% vs. 23.1% vs. 83.3%, P = 0.01). TB was diagnosed at HIV presentation in 11/29 children (37.9%). Foreign-born children accounted for respectively 0%, 8% and 67% of the total number of children in each period (P ≤ 0.0001). One third had extrapulmonary TB; four children died (13.8%)., [Conclusion] In our cohort, the incidence of TB-HIV co-infection decreased with decline in immigration. In regions with adequate cART coverage and low TB transmission, paediatric TB-HIV coinfection is uncommon, but associated with significant morbidity. Strategies for TB surveillance, diagnosis and treatment in this vulnerable population should be reinforced., This study was supported by the Spanish National Pediatric Network for HIV infected Children and Adolescents (CoRISpe) integrated in the Spanish AIDS Research Network (RIS), and supported by Instituto de Salud Carlos III, Spanish Health Ministry [Grant n8 RD16/0025/0024 and RD06/0025] as part of the Plan RþDþI; and co-financed by ISCIII-Subdirecci ´on General de Evaluaci ´on and Fondo Europeo de Desarrollo Regional (FEDER ‘‘Una manera de hacer Europa’’), RIS-EPICLIN-18/2015. TS and BS are funded by Spanish Ministry of Health - Instituto de Salud Carlos III (ISCIII) and co-funded by the European Union (FEDER) [Contratos Juan Rod´es, Grant JR16/00021 (TS) and JR16/00036 (BSG)].

Zika virus; Diagnosis; Infection in utero Virus Zika; Diagnòstic; Infecció uterina Virus Zika; Diagnóstico; Infección uterina INTRODUCTION: Zika virus (ZIKV) has caused one of the most challenging global infectious epidemics in recent years because of its causal association with severe microcephaly and other congenital malformations. The diagnosis of viral infections usually relies on the detection of virus proteins or genetic material in clinical samples as well as on the infected host immune responses. Serial serologic testing is required for the diagnosis of congenital infection when diagnostic molecular biology is not possible. PATIENT CONCERNS: A 2-year-old girl, born to a mother with confirmed ZIKV infection during pregnancy, with a confirmed ZIKV infection in utero, showed at birth a severe microcephaly and clinical characteristics of fetal brain disruption sequence compatible with a congenital ZIKV syndrome (CZS). DIAGNOSIS: ZIKV-RNA and ZIKV-IgM serological response performed at birth and during the follow-up time tested always negative. Serial serologic ZIKV-IgG tests were performed to assess the laboratory ZIKV diagnosis, ZIKV-IgG seroreversion was observed at 21 months of age. ZIKV diagnosis of this baby had to be relied on her clinical and radiological characteristics that were compatible with a CZS. INTERVENTIONS: The patient was followed-up as per protocol at approximately 1, 4, 9, 12, 18-21, and 24 months of age. Neurological, radiological, audiological, and ophthalmological assessment were performed during this period of time. Prompt rehabilitation was initiated to prevent potential adverse long-term neurological outcomes. OUTCOMES: The growth of this girl showed a great restriction at 24 months of age with a weight of 8.5 kg (-2.5 z-score) and a head circumference of 40.5 cm (-4.8 z-score). She also had a great neurodevelopmental delay at the time of this report. CONCLUSION: We presume that as a consequence of prenatal ZIKV infection, the fetal brain and other organs are damaged before birth through direct injury. Following this, active infection ends during intrauterine life, and as a consequence the immune system of the infant is unable to build up a consistent immune response thereafter. Further understanding of the mechanisms taking part in the pathogenesis of ZIKV congenital infection is needed. This finding might change our paradigm regarding serological response in the ZIKV congenital infection.

Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBSs) collected for newborn screening has been assessed for retrospective diagnosis of congenital CMV (cCMV) infection, with variable results (sensitivities ranging from 34% to 100%). We aimed to assess the accuracy of this technique in Spain in a large patient series.Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients. cCMV was established on the presence of CMV DNA in any body fluid, by positive culture findings or by molecular techniques during the first 2 weeks of life. Children in whom cCMV had been excluded were used as negative controls. Neonatal DBS samples were collected from both groups. The presence of CMV DNA was assessed by rt-PCR (RealStar CMV, Altona, Germany) in a central laboratory.One-hundred three patients and 81 controls from 10 hospitals were included. The performance of CMV DNA determination in DBS for the diagnosis of cCMV was as follows (95% confidence interval): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58) and negative likelihood ratio 0.45 (0.36-0.56). Sensitivity increased with the birth viral load (bVL) log category. In cCMV patients, lower bVL was the single variable associated with a negative DBS rt-PCR result (P = 0.017).The sensitivity of CMV rt-PCR in DBS in our series was low and correlated with the bVL. Thus, a negative DBS result would not rule out cCMV infection, especially in patients with a low viremia level at birth.

Neonatal herpes simplex virus infections are rare, but are associated with significant morbidity and mortality. Most newborns acquire herpes simplex virus infection in the peripartum period. For peripartum transmission to occur, women must be shedding the virus in their genital tracts symptomatically or asymptomatically around the time of delivery. There are evidence-based interventions in pregnancy to prevent the transmission to the newborn. Caesarean section should be performed in the presence of herpetic lesions, and antiviral prophylaxis in the last weeks of pregnancy is recommended to suppress genital tract herpes simplex virus at the time of delivery. The diagnosis and early treatment of neonatal herpes simplex virus infections require a high index of suspicion, especially in the absence of skin lesions. It is recommended to rule out herpes simplex virus infections in those newborns with mucocutaneous lesions, central nervous system involvement, or septic appearance. The prognosis of newborns with skin, eye, and/or mouth disease in the high-dose acyclovir era is very good. Antiviral treatment not only improves mortality rates in disseminated and central nervous system disease, but also improves the rates of long-term neurodevelopmental impairment in the cases of disseminated disease. Interestingly, a 6-month suppressive course of oral acyclovir following the acute infection has improved the neurodevelopmental prognosis in patients with CNS involvement. Resumen: La infección herpética neonatal es una entidad muy poco frecuente pero que se asocia a una alta morbimortalidad. La mayor parte de los neonatos afectos adquieren la infección por virus herpes simplex en el periodo periparto. Para que ocurra esta transmisión es necesaria la excreción viral genital, con o sin síntomas, alrededor del momento del parto. Existen intervenciones basadas en la evidencia para prevenir la transmisión del virus herpes simplex al recién nacido. La realización de una cesárea en presencia de lesiones herpéticas, y la disminución de la excreción viral administrando en las últimas semanas del embarazo tratamiento antiviral a gestantes con herpes genital activo, son las mejores medidas preventivas de las que se dispone. El diagnóstico y tratamiento precoz del herpes neonatal requiere de un alto índice de sospecha, sobre todo en ausencia de lesiones cutáneas. Se recomienda descartar la infección por herpes neonatal en aquellos recién nacidos con lesiones cutaneomucosas, afectación del sistema nervioso central o cuadro séptico de origen no aclarado. El pronóstico de los neonatos con enfermedad cutánea en la era del aciclovir a dosis altas es excelente. El tratamiento antiviral disminuye la mortalidad de las formas diseminadas y con afectación exclusiva del sistema nervioso central, pero también mejora el pronóstico neurológico en los casos de enfermedad diseminada. De forma notable, la introducción del tratamiento supresor con aciclovir oral durante los meses siguientes a la infección aguda ha mejorado el pronóstico neurológico en los pacientes con afectación del sistema nervioso central.

Congenital human cytomegalovirus (HCMV) infection is the most common mother-to-child transmitted infection in the developed world. Certain aspects of its management remain a challenge. Urinary metabolic profiling is a promising tool for use in pediatric conditions. The aim of this study was to investigate the urinary metabolic profile in HCMV-infected infants and controls during acute care hospitalization. Urine samples were collected from 53 patients at five hospitals participating in the Spanish congenital HCMV registry. Thirty-one cases of HCMV infection and 22 uninfected controls were included. Proton nuclear magnetic resonance (1H-NMR) spectra were obtained using NOESYPR1D pulse sequence. The dataset underwent orthogonal projection on latent structures discriminant analysis to identify candidate variables affecting the urinary metabolome: HCMV infection, type of infection, sex, chronological age, gestational age, type of delivery, twins, and diet. Statistically significant discriminative models were obtained only for HCMV infection (p = 0.03) and chronological age (p &lt, 0.01). No significant differences in the metabolomic profile were found between congenital and postnatal HCMV infection. When the HCMV-infected group was analyzed according to chronological age, a statistically significant model was obtained only in the neonatal group (p = 0.01), with the differentiating metabolites being betaine, glycine, alanine, and dimethylamine. Despite the considerable variation in urinary metabolic profiles in a real-life setting, clinical application of metabolomics to the study of HCMV infection seems feasible.

Escherichia coli early-onset sepsis (EOS) is an important cause of mortality and morbidity in neonates, especially in preterm and very low birth weight (VLBW) newborns. The aim of our study was to evaluate potential changes in the clinical and microbiological characteristics of E. coli EOS in our setting. Epidemiological, clinical, and microbiological data from all neonates with proven E. coli EOS from January 1994 to December 2014 were retrospectively collected in a single tertiary care hospital in Barcelona (Spain). Seventy-eight E. coli EOS cases were analyzed. A slight increase in the incidence of E. coli EOS was observed during the study period. VLBW newborns remained the group with higher incidence (10.4 cases per 1000 live births) and mortality (35.3%). Systematic use of PCR increased E. coli EOS diagnosis, mainly in the term newborn group. There was an increase in resistant E. coli strains causing EOS, with especially high resistance to ampicillin and gentamicin (92.8 and 28.6%, respectively). Nonetheless, resistant strains were not associated with poorer clinical outcomes.There is an urgent need to reconsider the empirical therapy used in neonatal EOS, particularly in VLBW newborns. What is Known: • E. coli early-onset sepsis (EOS) and E. coli resistant strains have been described as overall stable but increasing in VLBW neonates ( 1.500 g) in previous studies. What is New: • Our study shows an increasing incidence of E. coli EOS in all age groups, overruling group B Streptoccocus for the last 10 years. E. coli resistant strains also increased equally in all age groups, with high resistance rates to our first line antibiotics (ampicillin and gentamicin). • Empiric antibiotic therapy of EOS, mainly in VLBW newborns, should be adapted to this new scenario.

BACKGROUND: DNA detection of human cytomegalovirus (hCMV) in cerebrospinal fluid (CSF) by polymerase chain reaction (PCR) is a marker of central nervous system (CNS) involvement in congenital hCMV infection (cCMV), but its prognostic value is unknown. METHODS: A multicenter, retrospective study was performed using the Spanish Congenital Cytomegalovirus Infection Database (REDICCMV; http://www.cmvcongenito.es). Newborns with cCMV and a lumbar puncture performed were included and classified according to their hCMV-PCR in CSF result (positive/negative). Clinical characteristics, neuroimaging abnormalities, plasma viral load, and audiological and neurological outcomes of both groups were compared. RESULTS: A total of 136 neonates were included in the study: 21 (15.4%) with positive CSF hCMV-PCR and 115 (84.6%) with negative results. Seventeen patients (81%) in the positive group were symptomatic at birth compared with 52.2% of infants in the negative group (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.28-14.1; P = .01). Only 4 asymptomatic newborns (6.8%) had a positive CSF hCMV-PCR. There were no differences between groups regarding the rate of microcephaly, neuroimaging abnormalities, neurological sequelae at 6 months of age, or plasma viral load. Sensorineural hearing loss (SNHL) at birth was associated with a positive CSF hCMV-PCR result (OR, 3.49; 95% CI, 1.08-11.27; P = .04), although no association was found at 6 months of age. CONCLUSIONS: A positive hCMV-PCR result in CSF is associated with symptomatic cCMV and SNHL at birth. However, no differences in neuroimaging studies, plasma viral load, or outcomes at 6 months were found. These results suggest that hCMV-PCR in CSF may not be a useful prognostic marker in cCMV. Sin financiación 9.117 JCR (2017) Q1, 11/155 Immunology, 3/88 Infectious Diseases, 11/125 Microbiology UEM

Primary cutaneous aspergillosis is rare in premature infants. It requires combined medical and surgical strategies. Liposomal amphotericin B is recommended as first-line therapy, but salvage regimens with others antifungal agents, such as voriconazole, have been reported. Voriconazole's pharmacodynamics is unknown in this population. We report a case of severe toxicity to voriconazole in a preterm patient with primary cutaneous aspergillosis.

OBJECTIVES To evaluate voriconazole plasma level monitoring in immunocompromised children and determine the relationship of plasma levels with dose, safety and efficacy. METHODS We used a prospective study including all consecutive children with invasive fungal infection (IFI) treated with voriconazole between August 2008 and May 2010. IFI diagnosis and clinical outcome evaluation were based on European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group ('EORTC/MSG') definitions. RESULTS A total of 196 voriconazole plasma trough measurements from 30 patients (median age 10 years) obtained during 2135 days of voriconazole therapy were analysed. Nineteen patients (63%) presented with proven or probable IFI. Voriconazole plasma levels varied widely and 73% of patients required dose adjustment. The median voriconazole dose was 20 mg/kg/day and the median duration of therapy was 6 weeks. Age 5 was the smallest value defining two groups on which the correlation between dose and plasma levels had a different behaviour, and this relationship was especially significant for patients

Staphylococcus aureus is a major cause of bacteremia in children and is associated with high morbidity. Complete data are lacking on the incidence, related risk factors and mortality associated with this infection.Descriptive study including patients younger than 16 years admitted to a tertiary reference hospital, with blood cultures exclusively positive for S. aureus. Four study periods were established: period 1, 1995-1999; period 2, 2000-2002; period 3, 2006-2008 and period 4, 2010-2012.In total, 269 episodes of S. aureus bacteremia (SAB) occurred in 242 patients. Over the total time studied, the incidence increased from 1.3 to 3.3 cases per 1000 patients hospitalized (relative risk: 2.71; 95% confidence interval: 1.85-3.95) and mortality decreased from 18% to 6% (P = 0.008). There were no differences in the resistance patterns of S. aureus strains. The prevalence of methicillin-resistant S. aureus (MRSA) increased from 3% to 13% between periods 1 and 2 and decreased from 14% to 3% between periods 3 and 4 (P = 0.011). The 30-day cumulative mortality was 3.3%, and the SAB-related mortality was 1.5%. Nosocomial acquisition and age 12-16 years were factors independently related with death on multivariate analysis.The incidence of SAB tripled during the years studied but remained stable in the last period. Antimicrobial resistances did not increase. Although a decrease in mortality was documented, approximately half the 30-day cumulative mortality was caused by SAB.