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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.
Subject(s)
COVID-19 Vaccines , COVID-19 , Hospitalization , Mass Vaccination , SARS-CoV-2 , Vaccine Efficacy , Humans , COVID-19/prevention & control , COVID-19/epidemiology , Chile/epidemiology , Middle Aged , Hospitalization/statistics & numerical data , Male , Female , Adult , Aged , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Case-Control Studies , Adolescent , SARS-CoV-2/immunology , Mass Vaccination/methods , Mass Vaccination/statistics & numerical data , Young Adult , Child , Child, Preschool , Infant , Cohort Studies , Immunization Programs , Aged, 80 and overABSTRACT
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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BACKGROUND: Adjunctive diagnostic studies (aDS) are recommended to identify occult dissemination in patients with candidemia. Patterns of evaluation with aDS across pediatric settings are unknown. METHODS: Candidemia episodes were included in a secondary analysis of a multicenter comparative effectiveness study that prospectively enrolled participants age 120 days to 17 years with invasive candidiasis (predominantly candidemia) from 2014 to 2017. Ophthalmologic examination (OE), abdominal imaging (AbdImg), echocardiogram, neuroimaging, and lumbar puncture (LP) were performed per clinician discretion. Adjunctive diagnostic studies performance and positive results were determined per episode, within 30 days from candidemia onset. Associations of aDS performance with episode characteristics were evaluated via mixed-effects logistic regression. RESULTS: In 662 pediatric candidemia episodes, 490 (74%) underwent AbdImg, 450 (68%) OE, 426 (64%) echocardiogram, 160 (24%) neuroimaging, and 76 (11%) LP; performance of each aDS per episode varied across sites up to 16-fold. Longer durations of candidemia were associated with undergoing OE, AbdImg, and echocardiogram. Immunocompromised status (58% of episodes) was associated with undergoing AbdImg (adjusted odds ratio [aOR] 2.38; 95% confidence intervals [95% CI] 1.51-3.74). Intensive care at candidemia onset (30% of episodes) was associated with undergoing echocardiogram (aOR 2.42; 95% CI 1.51-3.88). Among evaluated episodes, positive OE was reported in 15 (3%), AbdImg in 30 (6%), echocardiogram in 14 (3%), neuroimaging in 9 (6%), and LP in 3 (4%). CONCLUSIONS: Our findings show heterogeneity in practice, with some clinicians performing aDS selectively, potentially influenced by clinical factors. The low frequency of positive results suggests that targeted application of aDS is warranted.
Subject(s)
Candidemia , Candidiasis, Invasive , Humans , Child , Aged, 80 and over , Candidemia/diagnosis , Candidemia/microbiology , Candidiasis, Invasive/drug therapy , Logistic Models , Cohort Studies , Risk Factors , Antifungal Agents/therapeutic useABSTRACT
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.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Adolescent , Invasive Fungal Infections/epidemiology , Neoplasms/complications , Chile/epidemiology , Retrospective Studies , Multicenter Study , Chemoprevention/methods , Febrile Neutropenia/epidemiology , Invasive Fungal Infections/prevention & control , Fungi/isolation & purification , Hospitals, Public/statistics & numerical data , Anemia, Aplastic/epidemiology , Antifungal Agents/administration & dosageABSTRACT
PURPOSE: To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. METHODS: The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. RESULTS: We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. CONCLUSION: The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.
Subject(s)
Febrile Neutropenia , Hematopoietic Stem Cell Transplantation , Neoplasms , Neutropenia , Child , Humans , Antifungal Agents/therapeutic use , Neutropenia/drug therapy , Neoplasms/complications , Neoplasms/therapy , Fever/therapy , Fever/drug therapy , Anti-Bacterial Agents/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Febrile Neutropenia/drug therapy , Febrile Neutropenia/etiologyABSTRACT
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.
Subject(s)
Humans , Child , Communicable Diseases , Febrile Neutropenia/drug therapy , Neoplasms/complications , Consensus , Fever , Latin AmericaABSTRACT
BACKGROUND: Invasive candidiasis is the most common invasive fungal disease in children and adolescents, but there are limited pediatric-specific antifungal effectiveness data. We compared the effectiveness of echinocandins to triazoles or amphotericin B formulations (triazole/amphotericin B) as initial directed therapy for invasive candidiasis. METHODS: This multinational observational cohort study enrolled patients aged >120 days and <18 years with proven invasive candidiasis from January 1, 2014, to November 28, 2017, at 43 International Pediatric Fungal Network sites. Primary exposure was initial directed therapy administered at the time qualifying culture became positive for yeast. Exposure groups were categorized by receipt of an echinocandin vs receipt of triazole/amphotericin B. Primary outcome was global response at 14 days following invasive candidiasis onset, adjudicated by a centralized data review committee. Stratified Mantel-Haenszel analyses estimated risk difference between exposure groups. RESULTS: Seven-hundred and fifty invasive candidiasis episodes were identified. After exclusions, 541 participants (235 in the echinocandin group and 306 in the triazole/amphotericin B group) remained. Crude failure rates at 14 days for echinocandin and triazole/amphotericin B groups were 9.8% (95% confidence intervals [CI]: 6.0% to 13.6%) and 13.1% (95% CI: 9.3% to 16.8%), respectively. The adjusted 14-day risk difference between echinocandin and triazole/amphotericin B groups was -7.1% points (95% CI: -13.1% to -2.4%), favoring echinocandins. The risk difference was -0.4% (95% CI: -7.5% to 6.7%) at 30 days. CONCLUSIONS: In children with invasive candidiasis, initial directed therapy with an echinocandin was associated with reduced failure rate at 14 days but not 30 days. These results may support echinocandins as initial directed therapy for invasive candidiasis in children and adolescents. CLINICAL TRIALS REGISTRATION: NCT01869829.
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BACKGROUND: In children with cancer and persistent high-risk febrile neutropenia (HRFN), cytokines/chemokines profiles can guide the differentiation of febrile neutropenia (FN) due to infections and episodes of unknown origin (FN-UO). METHODS: A prospective, multicenter study in Santiago, Chile included patients ≤ 18 years with cancer and HRFN. Clinical and microbiological studies were performed according to validated protocols. Serum levels of 38 cytokines/chemokines were determined on day 4 of persistent HRFN. We performed comparisons between i) HRFN episodes with a detected etiological agent (FN-DEA) and FN-UO, and ii) bacterial versus viral infections. ROC curves were used to assess the discriminatory power of the analytes. RESULTS: 110 HRFN episodes were enrolled (median age 8 years, 53% female). Eighty-four patients were FN-DEA: 44 bacterial, 32 viral, and 8 fungal infections. Twenty-six cases were categorized as FN-UO. Both groups presented similar clinical and laboratory characteristics. Nineteen out of 38 analytes had higher concentrations in the FN-DEA versus FN-UO group. G-CSF, IL-6, and Flt-3L showed the highest discriminatory power to detect infection (AUC 0.763, 0.741, 0.701). Serum levels of G-CSF differentiated bacterial infections and IP-10 viral agents. A combination of G-CSF, IL-6, Flt-3L, and IP-10 showed an AUC of 0.839, 75% sensitivity, and 81% specificity. CONCLUSION: A specific immune response is present on day four of persistent HRFN in children with cancer. We propose a combined measure of serum concentrations of G-CSF, IL-6, IP-10, and Flt-3L, in order to predict the presence of an infectious agent as compared to an episode of FN with unknown origin.
Subject(s)
Chemokines/blood , Cytokines/blood , Febrile Neutropenia/blood , Neoplasms/blood , Child , Febrile Neutropenia/diagnosis , Febrile Neutropenia/microbiology , Febrile Neutropenia/virology , Female , Humans , Male , ROC Curve , Risk FactorsABSTRACT
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.
Subject(s)
Communicable Diseases , Febrile Neutropenia , Neoplasms , Child , Consensus , Febrile Neutropenia/drug therapy , Fever , Humans , Latin America , Neoplasms/complicationsABSTRACT
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.
Subject(s)
Antifungal Agents/therapeutic use , Chemotherapy-Induced Febrile Neutropenia/complications , Invasive Fungal Infections/drug therapy , Mannans/blood , Neoplasms/complications , Aspergillosis/drug therapy , Case-Control Studies , Child , Female , Galactose/analogs & derivatives , Hematologic Neoplasms/complications , Humans , Invasive Pulmonary Aspergillosis/drug therapy , MaleABSTRACT
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.
Subject(s)
Candida/isolation & purification , Candidemia/epidemiology , Adolescent , Adult , Aged , Candidemia/microbiology , Child , Chile/epidemiology , Epidemiological Monitoring , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , Survival Rate , Young AdultABSTRACT
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.
Subject(s)
Antifungal Agents/therapeutic use , Chemoprevention/methods , Febrile Neutropenia/complications , Invasive Fungal Infections/drug therapy , Invasive Fungal Infections/prevention & control , Neoplasms/complications , Neoplasms/therapy , Child , Child, Preschool , Chile , Female , Humans , Invasive Fungal Infections/mortality , Length of Stay , Male , Prospective Studies , Survival Analysis , Treatment OutcomeABSTRACT
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.
Subject(s)
Otitis Media/epidemiology , Pneumococcal Infections/prevention & control , Pneumococcal Vaccines/administration & dosage , Streptococcus pneumoniae/immunology , Acute Disease , Case-Control Studies , Chile/epidemiology , Emergency Service, Hospital/statistics & numerical data , Female , Humans , Immunization Programs , Infant , Male , RegistriesABSTRACT
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.
Subject(s)
Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Immunocompromised Host , Maxillary Sinusitis/therapy , Mucormycosis/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology , Caspofungin , Child, Preschool , Echinocandins/therapeutic use , Female , Humans , Lipopeptides , Maxillary Sinusitis/microbiology , Mucormycosis/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
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.
Subject(s)
Child, Preschool , Female , Humans , Amphotericin B/therapeutic use , Antifungal Agents/therapeutic use , Immunocompromised Host , Maxillary Sinusitis/therapy , Mucormycosis/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/microbiology , Echinocandins/therapeutic use , Maxillary Sinusitis/microbiology , Mucormycosis/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Tomography, X-Ray Computed , Treatment OutcomeABSTRACT
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.
Subject(s)
Febrile Neutropenia/etiology , Leukemia, Myeloid, Acute/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Child , Febrile Neutropenia/drug therapy , Humans , Prospective Studies , Severity of Illness IndexABSTRACT
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.
Subject(s)
Child , Humans , Febrile Neutropenia/etiology , Leukemia, Myeloid, Acute/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Febrile Neutropenia/drug therapy , Prospective Studies , Severity of Illness IndexABSTRACT
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.
Subject(s)
Candida , Candidiasis/mortality , Adult , Aged , Amphotericin B/chemistry , Candida albicans , Candida glabrata , Candida tropicalis , Candidiasis/epidemiology , Deoxycholic Acid/chemistry , Drug Combinations , Female , Fluconazole/therapeutic use , Humans , Incidence , Male , Mexico , Middle Aged , Proportional Hazards Models , Prospective Studies , Regression Analysis , Risk Factors , Tertiary Care Centers , Treatment OutcomeABSTRACT
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.
Subject(s)
Mercaptopurine/administration & dosage , Methyltransferases/genetics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyrophosphatases/genetics , Adolescent , Alleles , Child , Child, Preschool , Female , Genotype , Humans , Male , Polymorphism, Single Nucleotide , Precursor Cell Lymphoblastic Leukemia-Lymphoma/pathologyABSTRACT
BACKGROUND: Active surveillance is necessary for improving the management and outcomes of patients with candidemia. The aim of this study was to describe the epidemiologic and clinical features of candidemia in pediatric patients in Latin America. METHOD: Prospective, multicenter, surveillance study of candidemia in a pediatric population from 23 hospitals in 8 Latin America countries between November 2008 and October 2010. RESULTS: Three hundred and two cases of candidemia were reported with a median incidence of 0.81/1000 admissions. Eighty nine (29%) were neonates. The main risk factors were prematurity, intensive care unit (ICU) admission, parenteral nutrition, respiratory disease and mechanical ventilation in neonates and malignancy, neutropenia, neurological disease and previous use of corticosteroids in children. The main species isolated in neonates and children were Candida albicans (43.8% and 35.7%), Candida parapsilosis (27.0% and 26.3%) and Candida tropicalis (14.6% and 14.6%), respectively. The most frequent antifungal therapy used in neonates and children was deoxycholate-amphotericin-B (43.8% and 29.1%) and fluconazole (28.1% and 53.1%). Seventeen neonates (19.1%) and 20 children (9.4%) did not receive antifungal therapy. The 30-day survival rate was 60% in neonates and 72% in children (P = 0.02). Survival was significantly higher in treated than in nontreated neonates (72% vs. 24%; P < 0.001). A multivariate analysis showed that independent predictors for 30-day mortality in children were renal disease (odds ratio: 4.38, 95% confidence interval: 1.92-10.1, P < 0.001) and receipt of corticosteroids (odds ratio: 2.08, 95% confidence interval: 1.04-4.17, P = 0.04). CONCLUSIONS: To our knowledge, this is the first prospective, multicenter surveillance study of candidemia in children in Latin America. This epidemiologic information may provide us with methods to improve preventive, diagnostic and therapeutic strategies in our continent.
