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PURPOSE OF REVIEW: The scope of this review is to understand the epidemiology and potential role of respiratory viral infections in children with cancer and febrile neutropenia, as well as in children, undergoing hematopoietic stem cell transplantation. Early detection of respiratory viral infections through molecular diagnostic techniques has allowed recent randomized clinical studies to advance the possibility of more rational use of antimicrobials in this susceptible population. RECENT FINDINGS: Progress has been made in the early detection of respiratory viruses in episodes of fever and neutropenia in children with cancer. In selected patients who meet specific clinical safety criteria and have negative bacterial cultures, it has been possible to safely and effectively discontinue antimicrobials. This has been validated in recent randomized clinical studies. However, more evidence is still needed for a similar indication in children, undergoing hematopoietic stem cell transplantation with viral respiratory infection episodes. SUMMARY: Understanding the role of respiratory viral infections in populations of immunocompromised children may contribute to a more rational use of antimicrobials and, in the near future, may help to decrease antimicrobial resistance in this susceptible population.
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Neutropenia Febril , Trasplante de Células Madre Hematopoyéticas , Huésped Inmunocomprometido , Neoplasias , Infecciones del Sistema Respiratorio , Virosis , Humanos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones del Sistema Respiratorio/virología , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Niño , Neoplasias/complicacionesRESUMEN
BACKGROUND: Invasive fungal diseases (IFD) are high morbidity and mortality infections in children with cancer suffering episodes of high-risk febrile neutropenia (HRFN). IFD epidemiology has changed in the last two decades, with an increasing incidence in recent years due to the growing number of immunocompromised children at risk for IFD. The aim of this study was to evaluate the incidence of IFD in children with cancer in the period 2016-2020 compared to 2004-2006 in six hospitals in Chile. METHODS: Prospective, multicentre study, carried out between 2016 and 2020 in six hospitals in Chile. The defined cohort corresponds to a dynamic group of HRFN episodes in patients <18 years old with cancer, who at the fourth day of evolution still presented fever and neutropenia (persistent HRFN). Each episode was followed until resolution of FN. The incidence of IFD was calculated between 2016 and 2020 and compared with data obtained in the period 2004-2006. The incidence rate was estimated. RESULTS: A total of 777 episodes of HRFN were analysed; 257 (33.1%) were considered as persistent-HRFN occurring in 174 patients. The median age was 7 years (IQR: 3-12 years) and 52.3% (N = 91) were male. Fifty-three episodes of IFD were detected: 21 proven, 14 probable and 18 possible. Possible IFD were excluded, leaving 239 episodes of persistent-HRFN with an IFD incidence of 14.6% (95% CI 10.5-19.9) and an incidence rate of 13.6 IFD cases per 1000 days of neutropenia (95% CI 9.5-20.0). Compared to 2004-2006 cohort (incidence: 8.5% (95% CI 5.2-13.5)), a significant increase in incidence of 6.1% (95% CI 0.2-12.1, p = .047) was detected in cohorts between 2016 and 2020. CONCLUSION: We observed a significant increase in IFD in 2016-2020, compared to 2004-2006 period.
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Infecciones Fúngicas Invasoras , Neoplasias , Humanos , Chile/epidemiología , Masculino , Estudios Prospectivos , Niño , Femenino , Preescolar , Infecciones Fúngicas Invasoras/epidemiología , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Neoplasias/epidemiología , Neoplasias/complicaciones , Incidencia , Huésped Inmunocomprometido , Adolescente , Lactante , Antineoplásicos/uso terapéuticoRESUMEN
BACKGROUND: Case-control studies involving test-negative (TN) and syndrome-negative (SN) controls are reliable for evaluating influenza and rotavirus vaccine effectiveness (VE) during a random vaccination process. However, there is no empirical evidence regarding the impact in real-world mass vaccination campaigns against SARS-CoV-2 using TN and SN controls. OBJECTIVE: To compare in the same population the effectiveness of SARS-CoV-2 vaccination on COVID-19-related hospitalization rates across a cohort design, TN and SN designs. METHOD: We conducted an unmatched population-based cohort, TN and SN case-control designs linking data from four data sources (public primary healthcare system, hospitalization registers, epidemiological surveillance systems and the national immunization program) in a Chilean municipality (Rancagua) between March 1, 2021 and August 31, 2021. The outcome was COVID-19-related hospitalization. To ensure sufficient sample size in the unexposed group, completion of follow-up in the cohort design, and sufficient time between vaccination and hospitalization in the case-control design, VE was estimated comparing 8-week periods for each individual. RESULTS: Among the 191,505 individuals registered in the primary healthcare system of Rancagua in Chile on March 1, 2021; 116,453 met the cohort study's inclusion criteria. Of the 9,471 hospitalizations registered during the study period in the same place, 526 were COVID-19 cases, 108 were TN controls, and 1,628 were SN controls. For any vaccine product, the age- and sex-adjusted vaccine effectiveness comparing fully and nonvaccinated individuals was 67.2 (55.7-76.3) in the cohort design, whereas it was 67.8 (44.1-81.4) and 77.9 (70.2-83.8) in the TN and SN control designs, respectively. CONCLUSION: The VE of a COVID-19 vaccination program based on age and risk groups tended to differ across the three observational study designs. The SN case-control design may be an efficient option for evaluating COVID-19 VE in real-world settings.
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Vacunas contra la COVID-19 , COVID-19 , Hospitalización , Vacunación Masiva , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/epidemiología , Chile/epidemiología , Persona de Mediana Edad , Hospitalización/estadística & datos numéricos , Masculino , Femenino , Adulto , Anciano , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Estudios de Casos y Controles , Adolescente , SARS-CoV-2/inmunología , Vacunación Masiva/métodos , Vacunación Masiva/estadística & datos numéricos , Adulto Joven , Niño , Preescolar , Lactante , Estudios de Cohortes , Programas de Inmunización , Anciano de 80 o más AñosRESUMEN
OBJECTIVES: To validate the efficacy and safety of withholding antimicrobial therapy in a new cohort of children with cancer and febrile neutropenia (FN) having a demonstrated viral respiratory tract infection. METHODS: Prospective, multicenter, noninferiority, randomized study, approved by the ethical committee, in children presenting with FN at seven hospitals in Chile, evaluated at admission for diagnosis of bacterial and viral pathogens. Children who were positive for a respiratory virus, negative for a bacterial pathogen, and had a favourable evolution after 48-72 hours of antimicrobial therapy were randomized to either maintain or withhold antimicrobial therapy. The primary endpoint was the percentage of episodes with an uneventful resolution, whereas the secondary endpoints were days of fever, days of hospitalization, requirement of antimicrobial treatment readministration, sepsis, paediatric intensive care unit admission, and death. RESULTS: A total of 301 of 939 children with FN episodes recruited between March 2021 and December 2023 had a respiratory virus as a unique identified microorganism, of which 139 had a favourable evolution at 48-72 hours and were randomized, 70 to maintain and 69 to withdraw antimicrobial therapy. The median days of antimicrobial therapy was 5 (IQR 3-6) versus 3 (IQR 3-6) days (p < 0.001), with similar frequency of uneventful resolution 66/70 (94%) and 66/69 (96%); relative risk, 1.01; (95% CI, 0.93 to 1.09), absolute risk difference 0.01; (95% CI, -0.05 to 0.08) and similar number of days of fever and days of hospitalization. No cases of sepsis, paediatric intensive care unit admission, or death were reported. DISCUSSION: We validated the strategy of withdrawal antimicrobial therapy in children with FN and viral respiratory tract infection based on clinical and microbiological/molecular diagnostic criteria. This will enable advances in antimicrobial stewardship strategies with a possible future impact on antimicrobial resistance.
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Neoplasias , Infecciones del Sistema Respiratorio , Virosis , Humanos , Masculino , Femenino , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Infecciones del Sistema Respiratorio/virología , Niño , Preescolar , Estudios Prospectivos , Virosis/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Neoplasias/complicaciones , Chile , Neutropenia Febril/tratamiento farmacológico , Lactante , Privación de Tratamiento , Fiebre/tratamiento farmacológico , Resultado del Tratamiento , Antiinfecciosos/uso terapéutico , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Antibacterianos/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Hospitalización , AdolescenteRESUMEN
INTRODUCCIÓN: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. OBJETIVO: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. MÉTODOS: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. RESULTADOS: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. CONCLUSIÓN: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.
BACKGROUND: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). AIM: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. METHODS: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. RESULTS: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. CONCLUSION: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.
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Humanos , Masculino , Femenino , Preescolar , Niño , Adolescente , Infecciones Fúngicas Invasoras/epidemiología , Neoplasias/complicaciones , Chile/epidemiología , Estudios Retrospectivos , Estudio Multicéntrico , Quimioprevención/métodos , Neutropenia Febril/epidemiología , Infecciones Fúngicas Invasoras/prevención & control , Hongos/aislamiento & purificación , Hospitales Públicos/estadística & datos numéricos , Anemia Aplásica/epidemiología , Antifúngicos/administración & dosificaciónRESUMEN
Resumen El Comité de Infecciones en el Niño Inmunocomprometido de la Sociedad Latinoamericana de Infectología Pediátrica, entrega este documento de Consenso, llamado "Manejo de los episodios de neutropenia febril en niños con cáncer. Consenso de la Sociedad Latinoamericana de Infectología Pediátrica 2021". El documento contiene recomendaciones sobre aspectos de prevención, predicción, diagnóstico, tratamiento y pronóstico de los episodios de fiebre y neutropenia, incluyendo recomendaciones específicas sobre: Análisis de ingreso; evaluación, ajustes y duración de terapias antimicrobianas; diagnóstico y manejo de infección fúngica invasora; análisis de los principales focos clínicos de infección; condiciones ambientales necesarias para hospitales que atienden niños con cáncer y quimioprofilaxis. Se ha puesto especial énfasis en entregar las mejores recomendaciones para optimizar el manejo de los episodios de fiebre y neutropenia en niños con cáncer, buscando la equidad y la excelencia a través de todos los centros que atienden estos pacientes en América Latina.
Abstract The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.
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Humanos , Niño , Enfermedades Transmisibles , Neutropenia Febril/tratamiento farmacológico , Neoplasias/complicaciones , Consenso , Fiebre , América LatinaRESUMEN
The Committee for Infections in Immunocompromised Children of Sociedad Latinoamericana de Infectología Pediátrica, presents this Consensus document, titled "Management of episodes of febrile neutropenia in children with cancer. Consensus of the Sociedad Latinoamericana de Infectología Pediátrica 2021". The document includes recommendations on prevention, prediction, diagnosis, treatment and prognosis of episodes of fever and neutropenia, including specific recommendations on: Analysis at admission; evaluation, adjustments and duration of antimicrobial therapies; diagnosis and management of invasive fungal infection; analysis of the main clinical source of infections; environmental conditions necessary for hospitals caring for children with cancer and chemoprophylaxis. Special emphasis has been placed on providing the best recommendations to optimize the management of episodes of fever and neutropenia in children with cancer, with equity and excellence through all the centers that treat these patients in Latin America.
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Enfermedades Transmisibles , Neutropenia Febril , Neoplasias , Niño , Consenso , Neutropenia Febril/tratamiento farmacológico , Fiebre , Humanos , América Latina , Neoplasias/complicacionesRESUMEN
BACKGROUND: Invasive fungal disease is a major cause of morbidity and mortality in children with cancer and high-risk febrile neutropenia (HRFN). Repeated serum galactomannan (sGM) measurements have been described as an effective tool to guide therapy in adults under suspicion of invasive aspergillosis. However, the utility of this approach has not been reported in paediatric population. OBJECTIVES: To evaluate the usefulness of sGM measurements in initiating and modifying antifungal therapy (AFT) in children with cancer and persistent HRFN. PATIENTS/METHODS: Nested case-control study in children with cancer and persistent HRFN episodes, between July 2013 and January 2019. Patients were classified as cases and controls depending on if they received AFT or not, respectively. Through odds ratio analysis, we assessed the role of sGM positivity in the AFT initiation decision. Then, we analysed the group of patients that initiated AFT, and compared those who had AFT modifications and those who did not, analysing different sGM kinetics thresholds. RESULTS: A total of 191 episodes from children with persistent HRFN were enrolled, of which 107 received AFT and 84 did not. The median age was 7 years (IQR 4-12), 52% were male and 89% had a haematologic malignancy as underlying disease. Positive sGM was not associated with AFT initiation (OR 0.99, 95% CI 0.43-2.33, P = .99). A difference threshold in sGM Δ ≥ 0.3 sGM was significantly associated with AFT modification (OR 5.07, 95% CI 1.02- 25.70, P = .04). CONCLUSIONS: Our results suggest the utility of serial sGM sampling during AFT in children with persistent HRFN.
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Antifúngicos/uso terapéutico , Neutropenia Febril Inducida por Quimioterapia/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Mananos/sangre , Neoplasias/complicaciones , Aspergilosis/tratamiento farmacológico , Estudios de Casos y Controles , Niño , Femenino , Galactosa/análogos & derivados , Neoplasias Hematológicas/complicaciones , Humanos , Aspergilosis Pulmonar Invasiva/tratamiento farmacológico , MasculinoRESUMEN
BACKGROUND: Active surveillance is necessary for improving the management and outcome of patients with candidemia. The aim of this study was to describe epidemiologic and clinical features of candidemia in children and adults in tertiary level hospitals in Chile. METHODS: We conducted a prospective, multicenter, laboratory-based survey study of candidemia in 26 tertiary care hospitals in Chile, from January 2013 to October 2017. RESULTS: A total of 780 episodes of candidemia were included, with a median incidence of 0.47/1,000 admissions. Demographic, clinical and microbiological information of 384 cases of candidemia, from 18 hospitals (7,416 beds), was included in this report. One hundred and thirty-four episodes (35%) occurred in pediatric patients and 250 (65%) in adult population. Candida albicans (39%), Candida parapsilosis (30%) and Candida glabrata (10%) were the leading species, with a significant difference in the distribution of species between ages. The use of central venous catheter and antibiotics were the most frequent risk factors in all age groups (> 70%). Three hundred and fifteen strains were studied for antifungal susceptibility; 21 strains (6.6%) were resistant to fluconazole, itraconazole, voriconazole, anidulafungin or micafungin. The most commonly used antifungal therapies were fluconazole (39%) and echinocandins (36%). The overall 30-day survival was 74.2%, significantly higher in infants (82%) and children (86%) compared with neonates (72%), adults (71%) and elderly (70%). CONCLUSIONS: Our prospective, multicenter surveillance study showed a low incidence of candidemia in Chile, with high 30-day survival, a large proportion of elderly patients, C. glabrata as the third most commonly identified strain, a 6.6% resistance to antifungal agents and a frequent use of echinocandins.
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Candida/aislamiento & purificación , Candidemia/epidemiología , Adolescente , Adulto , Anciano , Candidemia/microbiología , Niño , Chile/epidemiología , Monitoreo Epidemiológico , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Tasa de Supervivencia , Adulto JovenRESUMEN
Objectives: To compare the efficacy of pre-emptive versus empirical antifungal therapy in children with cancer, fever and neutropenia. Methods: This was a prospective, multicentre, randomized clinical trial. Children presenting with persistent high-risk febrile neutropenia at five hospitals in Santiago, Chile, were randomized to empirical or pre-emptive antifungal therapy. The pre-emptive group received antifungal therapy only if the persistent high-risk febrile neutropenia was accompanied by clinical, laboratory, imaging or microbiological pre-defined criteria. The primary endpoint was overall mortality at day 30 of follow-up. Secondary endpoints included invasive fungal disease (IFD)-related mortality, number of days of fever, days of hospitalization and use of antifungal drugs, percentage of children developing IFD, requiring modification of initial treatment strategy and need for ICU. The trial was registered with Registro Brasileiro de Ensaios Clínicos (ReBEC) under trial number RBR-3m9d74. Results: A total of 149 children were randomized, 73 to empirical therapy and 76 to pre-emptive therapy. Thirty-two out of 76 (42%) children in the pre-emptive group received antifungal therapy. The median duration of antifungal therapy was 11 days in the empirical arm and 6 days in the pre-emptive arm (P < 0.001), with similar overall mortality (8% in the empirical arm and 5% in the pre-emptive arm, P = 0.47). IFD-related mortality was the same in both groups (3%, P = 0.97), as were the percentage of children with IFD (12%, P = 0.92) and the number of days of fever (9, P = 0.76). The number of days of hospitalization was 19 in the empirical arm and 17 in the pre-emptive arm (P = 0.15) and the need for ICU was 25% in the empirical arm and 20% in the pre-emptive arm (P = 0.47). Conclusions: Pre-emptive antifungal therapy was as effective as empirical antifungal therapy in children with cancer, fever and neutropenia, significantly reducing the use of antifungal drugs.
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Antifúngicos/uso terapéutico , Quimioprevención/métodos , Neutropenia Febril/complicaciones , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/prevención & control , Neoplasias/complicaciones , Neoplasias/terapia , Niño , Preescolar , Chile , Femenino , Humanos , Infecciones Fúngicas Invasoras/mortalidad , Tiempo de Internación , Masculino , Estudios Prospectivos , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
BACKGROUND: Streptococcus pneumoniae is the leading cause of acute otitis media (AOM). Ten-valent pneumococcal conjugated vaccine (PCV-10) was introduced to the Chilean National Immunization Program (NIP) in 2011. The aim of this study was to estimate the frequency of AOM in children <24 months of age attending the emergency department (ED) of Hospital Sótero del Río (HSR) 4 years before and 4 years after the introduction of PCV-10 in the Chilean NIP. METHODS: Register-based nested case-control study. Cases (n = 1907) were all children <24 months of age with a clinical diagnosis discharge of AOM at the ED of HSR, and controls (n = 244,334) were all other children <24 months of age attended at the same ED in the same time period, with any other discharge diagnosis. The data were obtained through HSR Statistical Service. RESULTS: In the study period, there was a mean of 30,695 children <24 months managed each year at the ED of HSR. The percentage with AOM in the prevaccine period was 0.94% and in the postvaccine period was 0.62%, respectively (P = 0.026). Exposure to the PCV-10 was associated with a decreased risk to develop AOM in children <24 months, with an odds ratio of 0.659 (95% confidence interval: 0.60-0.72). CONCLUSIONS: Our study showed a significant decrease in the percentage and risk of AOM in children <24 months of age who visited the ED of HSR after implementation of PCV-10 in the NIP in Chile.
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Otitis Media/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas/administración & dosificación , Streptococcus pneumoniae/inmunología , Enfermedad Aguda , Estudios de Casos y Controles , Chile/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Programas de Inmunización , Lactante , Masculino , Sistema de RegistrosRESUMEN
The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.
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Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Huésped Inmunocomprometido , Sinusitis Maxilar/terapia , Mucormicosis/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Caspofungina , Preescolar , Equinocandinas/uso terapéutico , Femenino , Humanos , Lipopéptidos , Sinusitis Maxilar/microbiología , Mucormicosis/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The fungi of the order Mucorales cause mucormycosis, which usually presents as an invasive fungal disease with rapid angioinvasion in immunocompromised patients. Rhinocerebral is the most common presentation. The lipid formulations of amphotericin B are used as primary treatment in invasive mucormycosis; the combined use of posaconazole could allow a reduction in the dose of amphotericin B improving tolerance and adherence to treatment. Caspofungin and amphotericin B association has been shown to be synergistic in vitro and effective in murine models. We present the case of a preschool patient that during the debut of acute lymphoblastic leukemia developed a rhinocerebral mucormycosis successfully responding to antifungal treatment with the combination of liposomal amphotericin and caspofungin.
Los hongos del orden Mucorales causan la mucormicosis, que se presenta habitualmente como una enfermedad fúngica invasora con rápida angioinvasión en pacientes inmunocomprometidos. La presentación rino-cerebral es la más frecuente. Las formulaciones lipídicas de anfotericina B se usan como tratamiento primario en las mucormicosis invasoras; el uso combinado de posaconazol podría permitir reducir la dosis de anfotericina B generando una mejor tolerancia y adherencia al tratamiento. La asociación de caspofungina con anfotericina ha demostrado acción sinérgica in vitro y eficacia en modelos murinos. Se presenta el caso de una niña preescolar que durante el debut de una leucemia linfoblástica aguda evolucionó con una mucormicosis rino-cerebral persistente, que respondió en forma exitosa al tratamiento antifúngico combinado de anfotericina liposomal y caspofungina.
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Preescolar , Femenino , Humanos , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , Huésped Inmunocomprometido , Sinusitis Maxilar/terapia , Mucormicosis/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/microbiología , Equinocandinas/uso terapéutico , Sinusitis Maxilar/microbiología , Mucormicosis/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
INTRODUCTION: Leukemia is the most common cancer in Chilean children. Acute lymphoblastic leukemia (ALL) is more prevalent and longer survival compared to acute myeloid leukemia (AML). AIMS: To describe episodes of febrile neutropenia (FN) in children with AML, determining frequency of infections as agent, focus and evolution, comparing children with ALL episodes. METHOD: A prospective multicenter study. Children presenting with FN at six hospitals in Santiago, Chile, were invited to participate in two consecutive FONDECYT projects, from April 2004 to June 2011. All patients were uniformly evaluated, recording epidemiological, clinical and laboratory variables. Information regarding FN episodes of children with LMA and LLA was used to this study. RESULTS: We evaluated 506 episodes of FN in children with leukemia: 173 children with AML and 333 in children with ALL. NF episodes in children with ALML showed significantly greater depth and duration of neutropenia, febrile remained a > period of time and had a worse clinical outcome, as evidenced by > hemodynamic instability, > sepsis, CRP > 90 mg/L for a longer time, more days of hospitalization, > frequency of hospitalization in ICU, > bacteremia, mainly by Streptococcus viridans group, > change of antimicrobial treatment, > use of antifungal therapy. CONCLUSIONS: This study demonstrates that FN episodes in children with ALML further evolve unfavorably, compared with episodes of FN in children with ALL. FN episodes in children with ALML require a more aggressive diagnostic and therapeutic approach, related to its severity.
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Neutropenia Febril/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Niño , Neutropenia Febril/tratamiento farmacológico , Humanos , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Introduction: Leukemia is the most common cancer in Chilean children. Acute lymphoblastic leukemia (ALL) is more prevalent and longer survival compared to acute myeloid leukemia (AML). Aims: To describe episodes of febrile neutropenia (FN) in children with AML, determining frequency of infections as agent, focus and evolution, comparing children with ALL episodes. Method: A prospective multicenter study. Children presenting with FN at six hospitals in Santiago, Chile, were invited to participate in two consecutive FONDECYT projects, from April 2004 to June 2011. All patients were uniformly evaluated, recording epidemiological, clinical and laboratory variables. Information regarding FN episodes of children with LMA and LLA was used to this study. Results: We evaluated 506 episodes of FN in children with leukemia: 173 children with AML and 333 in children with ALL. NF episodes in children with ALML showed significantly greater depth and duration of neutropenia, febrile remained a > period of time and had a worse clinical outcome, as evidenced by > hemodynamic instability, > sepsis, CRP > 90 mg/L for a longer time, more days of hospitalization, > frequency of hospitalization in ICU, > bacteremia, mainly by Streptococcus viridans group, > change of antimicrobial treatment, > use of antifungal therapy. Conclusions: This study demonstrates that FN episodes in children with ALML further evolve unfavorably, compared with episodes of FN in children with ALL. FN episodes in children with ALML require a more aggressive diagnostic and therapeutic approach, related to its severity.
Introducción: En Chile, la leucemia es el cáncer más frecuente en niños, siendo las dos principales leucemia linfoblástica aguda (LLA) y leucemia mieloide aguda (LMA). Objetivo: Describir los episodios de neutropenia febril (NF) observados en niños con LMA, determinando la frecuencia de infecciones según agente, foco y evolución, comparándolos con episodios de niños con LLA. Método: Estudio prospectivo, multicéntrico. Pacientes < de 18 años con NF que consultaron en uno de los seis hospitales del grupo PINDA de Santiago, Chile (abril de 2004-junio de 2011), enrolados en dos sucesivos proyectos FONDECYT. Se recogió de manera sistemática la información epidemiológica, clínica y de laboratorio relativa a cada episodio de NF; posteriormente se extrajo de la base de datos la información correspondiente a los pacientes con LMA y LLA. Resultados: Se evaluaron 506 episodios de NF en niños con leucemia: 173 en niños con LMA y 333 en niños con LLA. Los episodios de NF en niños con LMA presentaron significativamente mayor duración e intensidad de la neutropenia, se mantuvieron febriles por un mayor período de tiempo y presentaron una peor evolución clínica, evidenciada por mayor inestabilidad hemodinámica, mayor frecuencia de sepsis, PCR > 90 mg/L por un período más prolongado, más días de hospitalización, mayor frecuencia de hospitalización en UCI, mayor presencia de bacteriemia, principalmente por Streptococcus grupo viridans, mayor número de cambio de esquemas antimicrobianos y mayor uso de antifúngicos, particularmente de tipo empírico. Conclusiones: Este estudio demuestra que los episodios de NF en niños con LMA evolucionan en mayor medida en forma desfavorable, comparado con episodios de NF en niños con LLA. Los episodios de NF en niños con LMA requieren un enfoque diagnóstico y terapéutico más agresivo, relacionado a su gravedad.
Asunto(s)
Niño , Humanos , Neutropenia Febril/etiología , Leucemia Mieloide Aguda/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Neutropenia Febril/tratamiento farmacológico , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION: Larger populations at risk, broader use of antibiotics and longer hospital stays have impacted on the incidence of Candida sp. bloodstream infections (CBSI). OBJECTIVE: To determine clinical and epidemiologic characteristics of patients with CBSI in two tertiary care reference medical institutions in Mexico City. DESIGN: Prospective and observational laboratory-based surveillance study conducted from 07/2008 to 06/2010. METHODS: All patients with CBSI were included. Identification and antifungal susceptibility were performed using CLSI M27-A3 standard procedures. Frequencies, Mann-Whitney U test or T test were used as needed. Risk factors were determined with multivariable analysis and binary logistic regression analysis. RESULTS: CBSI represented 3.8% of nosocomial bloodstream infections. Cumulative incidence was 2.8 per 1000 discharges (incidence rate: 0.38 per 1000 patient-days). C. albicans was the predominant species (46%), followed by C. tropicalis (26%). C. glabrata was isolated from patients with diabetes (50%), and elderly patients. Sixty-four patients (86%) received antifungals. Amphotericin-B deoxycholate (AmBD) was the most commonly used agent (66%). Overall mortality rate reached 46%, and risk factors for death were APACHE II score ≥ 16 (OR = 6.94, CI95%â= 2.34-20.58, p<0.0001), and liver disease (OR = 186.11, CI95%â= 7.61-4550.20, p = 0.001). Full susceptibility to fluconazole, AmBD and echinocandins among C. albicans, C. tropicalis, and C. parapsilosis was observed. CONCLUSIONS: The cumulative incidence rate in these centers was higher than other reports from tertiary care hospitals from Latin America. Knowledge of local epidemiologic patterns permits the design of more specific strategies for prevention and preemptive therapy of CBSI.
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Candida , Candidiasis/mortalidad , Adulto , Anciano , Anfotericina B/química , Candida albicans , Candida glabrata , Candida tropicalis , Candidiasis/epidemiología , Ácido Desoxicólico/química , Combinación de Medicamentos , Femenino , Fluconazol/uso terapéutico , Humanos , Incidencia , Masculino , México , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Análisis de Regresión , Factores de Riesgo , Centros de Atención Terciaria , Resultado del TratamientoRESUMEN
BACKGROUND: Mercaptopurine (6-MP) plays a pivotal role in treatment of childhood acute lymphoblastic leukemia (ALL); however, interindividual variability in toxicity of this drug due to genetic polymorphism in 6-MP metabolizing enzymes has been described. We determined the prevalence of the major genetic polymorphisms in 6-MP metabolizing enzymes in Chilean children with ALL. METHODS: 103 Chilean pediatric patients with a confirmed diagnosis of ALL were enrolled. DNA was isolated from whole blood and genetic polymorphism in thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) coding genes were detected by polymorphism chain reaction-restriction fragment length (PCR-RFLP) assay. RESULTS: The total frequency of variant TPMT alleles was 8%. TPMT*2, TPMT*3A and TPMT*3B alleles were found in 0%, 7%, and 1% of patients, respectively. For ITPA, the frequency of P32T allele was 3%. We did not observe any homozygous variant for TPMT and ITPA alleles. We also analyzed a subgroup of 40 patients who completed the maintenance phase of ALL treatment, and we found that patients carrying a TPMT gene variant allele required a significantly lower median cumulative dosage and median daily dosage of 6-MP than patients carrying wild type alleles. CONCLUSION: TMPT genotyping appears an important tool to further optimize 6-MP treatment design in Chilean patients with ALL.
Asunto(s)
Mercaptopurina/administración & dosificación , Metiltransferasas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Pirofosfatasas/genética , Adolescente , Alelos , Niño , Preescolar , Femenino , Genotipo , Humanos , Masculino , Polimorfismo de Nucleótido Simple , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologíaRESUMEN
Infections with varicella-zoster virus (VVZ) in immunocompromised children imply a high mortality. There is no data about VVZ seroprevalence in children with cancer in our country. Aim: To determine the prevalence of VVZ antibodies in children with cancer who have undergone chemotherapy or have undergone a hematopoietic stem cell transplant. Methodology: collaborative, multicenter study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia from 6 hospitals belonging to the public health network in the Metropolitan Region between June 2004 and August 2006. These samples were stored at -70 ° C, and 200 of them were randomly chosen and analyzed to determine VVZ IgG (ELISA). Results: 179 samples from 179 children, 65% male. Ninety eigth/179 (55%) were positive, 72/179 (40%) negative and 9/179 (5%) indeterminate. Stratified by age, seropositive percentage was: 1 to 4 years 32%, 5-9 years 42%, 10-14 years 78%, over 15 years 88%. Conclusion: Forty percent of children treated for cancer are seronegative to VVZ infection, a frequency that decreases with age. These results support the adoption of preventive measures to avoid infection in this population of children at risk of developing a serious and possibly fatal illness.
Las infecciones por virus varicela-zoster (VVZ) en niños inmunocomprometidos presentan una alta morbi-mortalidad. Se desconoce la seroprevalencia de VVZ en niños con cáncer en nuestro medio. Objetivo: Determinar la prevalencia de anticuerpos anti VVZ en niños sometidos a tratamiento por cáncer (quimioterapia o trasplante de precursores hematopoyéticos). Método: Estudio colaborativo, multicéntrico. Se recolectaron muestras de suero de 281 niños con cáncer y episodios de neutropenia febril (NF) en seis hospitales de Santiago, entre junio 2004 y agosto 2006 y almacenadas a -70° Cº. Doscientas muestras fueron seleccionadas al azar para determinación de IgG anti VVZ. Resultados: De las 200 muestras de suero obtenidas se excluyeron 21: 12 por ser muestras de un mismo paciente en diferentes episodios de NF y 9 por falta de información. Se analizaron las muestras de 179 niños, 65% de sexo masculino. Noventa y ocho resultaron positivos (55%), 72 negativos (40%) y 9 indeterminados (5%). Estratificado por edad: 1-4 años (32%), 5-9 años (42%), 10-14 años (78%) y mayores de 15 años (88%). Conclusión: 40% de los niños en tratamiento por cáncer son seronegativos para VVZ, condición que disminuye en pacientes con mayor edad. Estos resultados apoyan la adopción de medidas que eviten la infección en esta población de niños con riesgo de desarrollar una enfermedad grave y eventualmente fatal.
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Adolescente , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Varicela/epidemiología , /inmunología , Huésped Inmunocomprometido/inmunología , Neoplasias/inmunología , Anticuerpos Antivirales/sangre , Varicela/diagnóstico , Varicela/inmunología , Chile/epidemiología , Ensayo de Inmunoadsorción Enzimática , Prevalencia , Estudios SeroepidemiológicosRESUMEN
INTRODUCTION: To determine the etiology of invasive bacterial infection in high risk febrile neutropenia (HRFN) episodes in children with cancer is essential because of the favorable impact on mortality of the early empiric antibiotic treatment. OBJECTIVE: To determine the etiology of bacteremia in pediatric patients with cancer and HRFN in the National Child Program of Antineoplastic Drugs during the 2004-2009 period, and compare these agents and their antimicrobial susceptibility with the period 1994-1998 described in a previous study. METHODS: The causative agents of bacteremia were prospectively recorded in patients less than 18 years of age receiving chemotherapy for cancer with HRFN and positive blood cultures admitted to one of the six hospitals from the Child Program of Antineoplastic Drugs network during the period 2004-2009. RESULTS: 839 episodes of HRFN were identified; 181 blood cultures were positive in the following proportion: gram positive cocci (56%), gram negative bacilli (42%) and yeast (2%).The most common etiologic agents were Staphylococcus coagulase negative (25%), Escherichia. coli (20%), group viridans Streptococcus (14%), Staphylococcus aureus (13%) and Pseudomonas aeruginosa (9%). Comparing the two periods, the relative frequency of Streptococcus spp increased from 4 to 17%, coagulase negative Staphylococcus decreased from 44 to 25%, showing an increase in their resistance to oxacillin from 55% to 77%. CONCLUSIONS: We describe the main etiological agents from HRFN episodes in children with cancer in a 5 years period. This information could help for a better approach in the empirical antimicrobial therapy in this population.
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Bacteriemia/microbiología , Fiebre/microbiología , Bacterias Gramnegativas/clasificación , Bacterias Grampositivas/clasificación , Neoplasias/microbiología , Neutropenia/microbiología , Adolescente , Antibacterianos/farmacología , Niño , Chile , Femenino , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/aislamiento & purificación , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/aislamiento & purificación , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Estudios ProspectivosRESUMEN
BACKGROUND: The role of respiratory viral infections (RVIs) as a cause of overall fever and neutropenia (FN) episodes in children with cancer has been less characterized than bacterial infections. We conducted a study aimed to determine the frequency of RVI in children with low compared with high risk for invasive bacterial infection (IBI) FN episodes and compare the clinical outcome of RVI and mixed RV-bacterial infections. METHODS: Prospective, multicenter study in children with cancer and FN admitted to pediatric hospitals in Chile between May 2009 and January 2011. Children were evaluated by clinical examination and laboratory tests, including bacterial cultures and their risk for IBI. Nasopharyngeal sample was obtained for the detection of 17 respiratory viruses using polymerase chain reaction-DNA microarray platform. RESULTS: A total of 331 episodes of FN in 193 children were enrolled of whom 55% were male, with the median age of 7 years and 61% had a hematological malignancy. A viral and/or bacterial pathogen was detected in 67% (224/331) episodes. Overall, RVIs were associated with 57% of FN of which one-third were mixed RV-bacterial infections. Bacterial infection was detected in 29% (97/331). Children classified at admission as high risk for IBI had a similar overall proportion of RVI compared with low-risk group. Respiratory syncytial virus (31%) and rhinovirus (23%) were the most frequently detected respiratory viruses, followed by parainfluenza (12%) and influenza A (11%). Children detected with any respiratory virus had fewer days of hospitalization and a significantly lower probability of hypotension and admission to pediatric intensive care unit irrespective of their risk classification status at admission when compared with children with mixed RV-bacterial or bacterial infections (P < 0.05). All children with a sole RVI had favorable outcome. CONCLUSIONS: RVIs were the most frequently detected agents irrespective of their initial risk assessment for IBI. The clinical outcome of mixed RVI was similar to sole RVI episodes as well as for bacterial infections compared with mixed viral-bacterial infections. Systematic and early detection of RVI in children with cancer and FN might help to optimize their management by reducing hospitalization and antimicrobial use.