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2.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-31272810

RESUMO

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.

3.
Medicine (Baltimore) ; 98(20): e15532, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31096455

RESUMO

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.


Assuntos
Complicações Infecciosas na Gravidez/diagnóstico , Infecção por Zika virus/diagnóstico , Encéfalo/anormalidades , Pré-Escolar , Feminino , Humanos , Microcefalia/etiologia , Gravidez , Testes Sorológicos , Espanha , Infecção por Zika virus/complicações
4.
Pediatr Infect Dis J ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30199483

RESUMO

BACKGROUND: Detection of cytomegalovirus (CMV) DNA by real-time polymerase chain reaction (rt-PCR) in dried blood spots (DBS) 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. METHODS: Ambispective, multicenter study including patients with confirmed cCMV from the Spanish Registry of cCMV patients (REDICCMV). 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, Hamburg, Germany) in a central laboratory. RESULTS: One-hundred and 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% CI): sensitivity 0.56 (0.47-0.65), specificity 0.98 (0.91-0.99), positive likelihood ratio 22.81 (5.74-90.58), 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). CONCLUSION: 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.

5.
Eur J Pediatr ; 176(9): 1227-1234, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28770413

RESUMO

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. CONCLUSIONS: 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.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Sepse Neonatal/tratamento farmacológico , Sepse Neonatal/epidemiologia , Adolescente , Adulto , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/sangue , Infecções por Escherichia coli/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Sepse Neonatal/sangue , Reação em Cadeia da Polimerase , Estudos Retrospectivos , Espanha/epidemiologia , Adulto Jovem
6.
Clin Infect Dis ; 64(10): 1335-1342, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28158709

RESUMO

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.


Assuntos
Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/diagnóstico , Citomegalovirus/isolamento & purificação , DNA Viral/líquido cefalorraquidiano , Infecções Assintomáticas , Citomegalovirus/genética , Infecções por Citomegalovirus/complicações , DNA Viral/sangue , DNA Viral/isolamento & purificação , Feminino , Doenças Fetais/virologia , Seguimentos , Perda Auditiva Neurossensorial/virologia , Humanos , Lactente , Recém-Nascido , Masculino , Microcefalia/virologia , Neuroimagem , Reação em Cadeia da Polimerase/métodos , Estudos Retrospectivos , Saliva/virologia , Punção Espinal , Carga Viral
7.
Medicine (Baltimore) ; 95(24): e3842, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27310962

RESUMO

To assess the safety and efficacy of rilpivirine in combination with emtricitabine and tenofovir (RPV/FTC/TDF) as a once-daily single-tablet regimen (STR) in HIV-1-infected children and adolescents we performed a multicenter case series study of HIV-1-infected patients. Inclusion criteria were initiation of therapy with RPV/FTC/TDF before the age of 18. Patients were divided into undetectable viral load (uVL) group, HIV-1 RNA < 20 copies/mL on stable combined antiretroviral therapy (cART), and detectable viral load (dVL) group, HIV-1 RNA ≥ 20 copies/mL at RPV/FTC/TDF initiation. Patients were monitored from the date of RPV/FTC/TDF initiation until June 30, 2015, RPV/FTC/TDF discontinuation or failure to follow-up. Seventeen patients (8 in uVL and 9 in dVL group) with age between 11.6 and 17.6 were included. Reasons for switching were toxicity (n = 4) and simplification (n = 4) in uVL; viral failure (n = 8) and cART initiation (n = 1) in the dVL group. After a median follow-up of 90 (uVL) and 40 weeks (dVL), 7/8 (86%) patients maintained and 8/9 (89%) achieved and maintained HIV-1 suppression. Median CD4 count increased from 542 to 780/µL (uVL, P = 0.069) and 480 to 830/µL (dVL, P = 0.051). Five patients (2 in uVL and 3 in dVL) improved their immunological status from moderate to no immunosuppression. Serum lipid profiles improved in both groups; cholesterol dropped significantly in the dVL group (P = 0.008). Grade 1 laboratory adverse events (AEs) were observed in 3 patients. No clinical AEs occurred. Adherence was complete in 9 patients (5 in uVL and 4 in dVL); 1 adolescent interrupted treatment. Once-daily STR with RPV/FTC/TDF may be a safe and effective choice in selected HIV-1-infected adolescents and children.


Assuntos
Emtricitabina/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1/genética , RNA Viral/análise , Tenofovir/administração & dosagem , Adolescente , Fármacos Anti-HIV/administração & dosagem , Criança , Quimioterapia Combinada , Feminino , Seguimentos , Infecções por HIV/virologia , Humanos , Masculino , Uso Off-Label , Estudos Retrospectivos , Resultado do Tratamento
8.
Pediatr Infect Dis J ; 35(6): 704-6, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26974892

RESUMO

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.


Assuntos
Antifúngicos/efeitos adversos , Aspergilose/tratamento farmacológico , Dermatomicoses/tratamento farmacológico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Voriconazol/efeitos adversos , Antifúngicos/administração & dosagem , Evolução Fatal , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Masculino , Insuficiência de Múltiplos Órgãos , Voriconazol/administração & dosagem
10.
J Antimicrob Chemother ; 67(3): 700-6, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22190607

RESUMO

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 <5 years old (Spearman's rank correlation coefficient=0.38213, P=0.008). For patients <5 years old the median dose to achieve therapeutic levels was 38.0 mg/kg/day (12-40.0) and for those ≥5 years old it was 15 mg/kg (4-52). Voriconazole plasma levels showed a significant relationship with early outcome (P=0.0268), but not late outcome (P=0.2015). Overall mortality was 42% and a significant relationship with voriconazole therapeutic plasma levels was not demonstrated. A significant relationship was established between plasma levels above normal range and skin and neurological toxicity (P=0.0001), but this could not be demonstrated for liver toxicity. CONCLUSIONS: Our study confirms the large variability in voriconazole trough plasma levels in children and a trend to non-linear pharmacokinetics in older patients. In addition, doses significantly higher than those recommended in younger children seem warranted and a significant relationship between plasma voriconazole above the normal range and some adverse events is confirmed.


Assuntos
Antifúngicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Micoses/tratamento farmacológico , Pirimidinas/administração & dosagem , Triazóis/administração & dosagem , Adolescente , Antifúngicos/efeitos adversos , Antifúngicos/farmacocinética , Criança , Pré-Escolar , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Hospedeiro Imunocomprometido , Incidência , Lactente , Masculino , Plasma/química , Estudos Prospectivos , Pirimidinas/efeitos adversos , Pirimidinas/farmacocinética , Resultado do Tratamento , Triazóis/efeitos adversos , Triazóis/farmacocinética , Voriconazol
11.
Enferm. infecc. microbiol. clín. (Ed. impr.) ; 28(10): 675-679, dic. 2010. tab, ilus
Artigo em Espanhol | IBECS | ID: ibc-95336

RESUMO

Introducción Desde la década de 1990 se describen cepas de Staphylococcus aureus resistente a la meticilina adquirido en la comunidad (SARM-AC) que afectan con frecuencia a niños y a adultos jóvenes sin factores de riesgo y cuya incidencia en España está en aumento. Métodos Se incluyó a los pacientes atendidos en el área pediátrica entre agosto de 2006 y enero de 2009 con cultivos positivos para SARM-AC. Los aislamientos de S. aureus se estudiaron mediante técnicas convencionales, su sensibilidad antimicrobiana mediante técnica de discodifusión y la presencia del gen mecA mediante reacción en cadena de la polimerasa (multiplex). La presencia de la leucocidina de Panton-Valentine se determinó mediante reacción en cadena de la polimerasa convencional. Se estudió el estado de portador en los pacientes y sus familiares. Resultados Se recogieron 15 aislamientos de SARM-AC de 12 pacientes sin factores de riesgo (entre 6 días y 14 años de edad). Ocho requirieron ingreso. La mitad de los enfermos eran de población no autóctona. La afectación de piel y partes blandas fue la forma clínica más frecuente (92%). Solo 2 tuvieron bacteriemia. Dos cepas tenían resistencia a macrólidos asociada a la resistencia a meticilina y una de ellas, además, a lincosamidas. Todas fueron productoras de leucocidina de Panton-Valentine. La evolución fue favorable. Se detectó una agrupación familiar de SARM-AC. Conclusión La infección por SARM-AC constituye una enfermedad emergente en nuestro medio. Su incidencia en España es aún baja, por lo que no se debe cambiar el tratamiento empírico de las infecciones cutáneas. El drenaje de las lesiones tiene un papel importante en su curación. La clindamicina o el cotrimoxazol es el tratamiento de elección de las formas leves o moderadas. El control de la propagación de SARM-AC constituye un nuevo reto en la actualidad (AU)


Introduction Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections were first reported in the 1990s. Young, healthy individuals are frequently affected. The incidence of CA-MRSA in Spain is increasing. Methods All children seen between August 2006 and January 2009 with CA-MRSA infections were included. The S. aureus isolates were studied by conventional techniques, their antibiotic susceptibility by agar disk diffusion, the presence of mecA gene was detected by multiplex polymerase chain reaction (PCR) and the gene encoding the Panton-Valentine leukocidin (PVL) by conventional PCR. CA-MRSA colonization was studied both in patients and their family members. Results CA-MRSA was isolated in 15 samples from 12 patients, aged between 6 days and 14 years. Half of them were not native. Eight patients required hospital admission. The most common clinical presentation was skin and soft tissue infection (92%). Secondary CA-MRSA bacteraemia was present in two patients. All strains were PVL producers and two were resistant to macrolides associated to methicillin resistance and one of them was also resistant to lincosamides. An intra-familial transmission was identified. The clinical outcome was favourable in all patients. Conclusion CA-MRSA infections are emerging in Spain. Empirical treatment of skin and soft tissue infections should not be changed, since their incidence is still low. The drainage of CA-MRSA suppurative infections plays an important role in their treatment. Clindamycin or trimethoprim-sulfamethoxazole should be used for mild or moderate skin and soft tissue infections. Controlling the spread of these strains presents a challenge in the community today (AU)


Assuntos
Humanos , Masculino , Feminino , Criança , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Infecções Comunitárias Adquiridas/imunologia , Leucocidinas/farmacocinética , Anti-Infecciosos/uso terapêutico , Clindamicina/uso terapêutico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
12.
Enferm Infecc Microbiol Clin ; 28(10): 675-9, 2010 Dec.
Artigo em Espanhol | MEDLINE | ID: mdl-20678828

RESUMO

INTRODUCTION: Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections were first reported in the 1990s. Young, healthy individuals are frequently affected. The incidence of CA-MRSA in Spain is increasing. METHODS: All children seen between August 2006 and January 2009 with CA-MRSA infections were included. The S. aureus isolates were studied by conventional techniques, their antibiotic susceptibility by agar disk diffusion, the presence of mecA gene was detected by multiplex polymerase chain reaction (PCR) and the gene encoding the Panton-Valentine leukocidin (PVL) by conventional PCR. CA-MRSA colonization was studied both in patients and their family members. RESULTS: CA-MRSA was isolated in 15 samples from 12 patients, aged between 6 days and 14 years. Half of them were not native. Eight patients required hospital admission. The most common clinical presentation was skin and soft tissue infection (92%). Secondary CA-MRSA bacteraemia was present in two patients. All strains were PVL producers and two were resistant to macrolides associated to methicillin resistance and one of them was also resistant to lincosamides. An intra-familial transmission was identified. The clinical outcome was favourable in all patients. CONCLUSION: CA-MRSA infections are emerging in Spain. Empirical treatment of skin and soft tissue infections should not be changed, since their incidence is still low. The drainage of CA-MRSA suppurative infections plays an important role in their treatment. Clindamycin or trimethoprim-sulfamethoxazole should be used for mild or moderate skin and soft tissue infections. Controlling the spread of these strains presents a challenge in the community today.


Assuntos
Doenças Transmissíveis Emergentes/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Abscesso/epidemiologia , Abscesso/microbiologia , Adolescente , Proteínas de Bactérias/genética , Toxinas Bacterianas/análise , Portador Sadio , Criança , Pré-Escolar , Doenças Transmissíveis Emergentes/microbiologia , Infecções Comunitárias Adquiridas/microbiologia , Resistência Microbiana a Medicamentos , Emigrantes e Imigrantes , Exotoxinas/análise , Saúde da Família , Hospitalização , Humanos , Lactente , Recém-Nascido , Leucocidinas/análise , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Proteínas de Ligação às Penicilinas , Infecções dos Tecidos Moles/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Espanha/epidemiologia , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Infecções Cutâneas Estafilocócicas/microbiologia
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