Impact of a structured educational programme for caregivers of children with cancer on parental knowledge of the disease and paediatric clinical outcomes during the first year of treatment.

OBJECTIVE: To assess the impact of a structured educational programme for caregivers of children with cancer on their level of knowledge about the disease and patient's clinical outcome. METHODS: This prospective, non-randomised, experimental study included caregivers of recently diagnosed children at two hospitals in Chile. Caregivers whose children were treated at the first centre were the structured education programme group (EPG), while the second hospital provided the standard care (SCG). We evaluated caregivers' level of knowledge on days 1, 10 and 90 as well as the children's clinical outcomes over 1 year of treatment. RESULTS: A total of 102 caregivers were enrolled between 2014 and 2015. Only the EPG showed a significant increase in knowledge between days 1 and 90. The rate of central venous catheter infections was significantly lower in the EPG versus SCG (7% versus 26%; p = .01). The risk ratio was 0.35 (95% CI = 0.13-0.94), and a log-rank test showed a statistically significant difference between the two groups (p = .018). There were also fewer Emergency Department visits in the EPG for fever episodes. CONCLUSION: Providing a structured education to caregivers increased their level of knowledge and improved the clinical outcome of their children during the first year of treatment.

[Etiologic diagnosis in meningitis and encephalitis molecular biology techniques]. / Diagnóstico etiológico en meningitis y encefalitis por técnicas de biología molecular.

INTRODUCTION: The aetiological study of infections of the central nervous system has traditionally been performed using bacterial cultures and, more recently, using polymerase chain reaction (PCR) for herpes simplex virus (HSV). Bacterial cultures may not have good performance, especially in the context of patients who have received antibiotics prior to sampling, and a request for HSV only by PCR reduces the information to only one aetiological agent. The aim of this study is to determine the infectious causes of meningitis and encephalitis, using traditional microbiology and molecular biology to improve the aetiological diagnosis of these diseases. PATIENTS AND METHOD: A prospective study was conducted on 19 patients with suspected meningitis, admitted to the Luis Calvo Mackenna Hospital in Santiago, Chile, from March 1, 2011 to March 30, 2012. After obtaining informed consent, the CSF samples underwent cytochemical study, conventional culture, multiplex PCR for the major producing bacterial meningitis (N. meningitidis, S. pneumoniae, H. influenzae), real-time single PCR for HSV-1 and 2, VZV, EBV, CMV, HHV-6 and enterovirus. Clinical and epidemiological data were also collected from the clinical records. RESULTS: Of the 19 patients analysed, 2 were diagnosed by conventional methods and 7 by adding molecular biology (increase to 37%). Three patients had meningitis due to S. pneumoniae, one due to Enterobacter cloacae, 2 patients meningoencephalitis HSV-1, and one VZV meningitis. CONCLUSIONS: The addition of PCR to conventional diagnostic methods in CNS infections increases the probability of finding the causal agent. This allows a more adequate, timely and rational management of the disease.

[Seroconversion in response to a reinforced primary hepatitis B vaccination in children with cancer]. / Seroconversión frente a primovacunación reforzada contra hepatitis B en niños con cáncer.

INTRODUCTION: Immune response against vaccine antigens may be impaired in children with cancer. The aim of this study was to evaluate the seroconversion response against hepatitis B vaccination (HBV) at the time of chemotherapy onset and/or remission in children with cancer. PATIENTS AND METHOD: Prospective, two-centre, controlled, non-randomised study conducted on children recently diagnosed with cancer, paired with healthy subjects. Cases received HBV at time 0, 1 and 6 months with DNA recombinant HBV at a dose of 20 and 40 µg if < or > than 10 years of age, respectively, at the time of diagnosis for solids tumours and after the remission in case of haematological tumours. Controls received the same schedule, but at of 10 and 20 µg doses, respectively. HBs antibodies were measured in serum samples obtained at 2, 8 and 12 months post-vaccination. Protective titres were defined as > 10 mIU/ml at 8th month of follow up. RESULTS: A total of 78 children with cancer and 25 healthy controls were analysed at month 8th of follow up. Seroconversion rates in the cancer group reached 26.9%, with no differences by age, gender or type of tumour (P = .13, .29, and .44, respectively). Control group seroconversion was 100% at the 8th month, with P < .0001 compared with the cancer group. At month 12 of follow up, just 31.9% of children with cancer achieved anti-HBs antibodies > 10 mIU/ml. CONCLUSIONS: Vaccination against hepatitis B with three doses of DNA recombinant vaccine at an increased concentration, administrated at the time of onset of chemotherapy and/or remission provided an insufficient immune response in a majority of children with cancer. More immunogenic vaccines should be evaluated in this special population, such as a third generation, with more immunogenic adjuvants, enhanced schedules at 0, 1, 2, 6 month, evaluation of antibody titres at month 8 and 12h to evaluate the need for further booster doses.

[Invasive candidiasis in newborns: diagnosis, treatment and prophylaxis]. / Candidiasis invasoras en recién nacidos: diagnóstico, tratamiento y prevención.

Invasive fungal infections have become an increasingly common problem in neonatal intensive care units (NICU). Invasive candidiasis (IC) is associated with substantial morbidity and mortality rates, especially in pre-term infants. The aim of this review is to suggest actions in monitoring, prevention, treatment and follow up of IC in the newborn infant.

[Microorganisms isolated from blood cultures and resistance profile in children with cancer and high-risk febrile neutropenia. Red PINDA, Chile, 2016-2021]. / Microorganismos aislados de hemocultivos y su perfil de resistencia en niños con cáncer y neutropenia febril de alto riesgo. Red PINDA, Chile, 2016-2021.

Bacteremia is a major cause of morbidity and mortality in patients with cancer and episodes of high-risk febrile neutropenia (HRFN). OBJECTIVE: To identify the frequency of microorganisms isolated from blood cultures (BC) and their antimicrobial resistance (R) profile in children with HRFN, compared with the same data from previous studies of the same group. METHOD: Prospective, multicenter, epidemiological surveillance study of microorganisms isolated from BC in patients under 18 years of age, from 7 PINDA network hospitals, between 2016 and 2021. RESULTS: 284 episodes of HRFN with positive BC were analyzed out of 1091 enrolled episodes (26%). Median age 7.2 years [3.0-12.3]. The main isolates were gram-negative bacilli (GNB) 49.2%, gram-positive cocci (GPC) 43.8%, and fungi 3.6%. The most frequently isolated microorganisms were viridans group Streptococci (VGS) (25.8%), Escherichia coli (19.8%), Pseudomonas spp. (11.2%), Klebsiella spp. (10.9%), and coagulase negative Staphylococci (CoNS) (10.9%). There was an increase in R to third-generation cephalosporins (p = 0.011) in GNB and to oxacillin in CoNS (p = 0.00), as well as a decrease in R to amikacin in non-fermenting GNB (p = 0.02) and to penicillin in VGS (p = 0.04). CONCLUSION: VGS is the main agent isolated in BC from pediatric patients with cancer and episodes of HRFN, followed by E. coli, Pseudomonas spp., and Klebsiella spp. Having epidemiological surveillance of microorganisms isolated from BC and their antimicrobial R profile is essential to favor the rational use of antimicrobials.

Landscape of Invasive Fusariosis in Pediatric Cancer Patients: Results of a Multicenter Observational Study From Latin America.

Invasive fusariosis (IF) is a life-threatening opportunistic infection that affects vulnerable hosts. We conducted a multicenter and multinational retrospective study to characterize the natural history and clinical management of IF in pediatric cancer patients. We selected patients <18 years old who were sequentially hospitalized in 10 Latin American medical centers with a diagnosis of IF between 2002 and 2021. Data were collected using an electronic case report form complemented by a dictionary of terms. We assessed mortality rates at 30, 60, and 90 days. We collected data from 60 episodes of IF (median age, 9.8 years) that were mostly documented in patients with hematologic cancer (70%). Other risk conditions found were lymphopenia (80%), neutropenia (76.7%), and corticosteroid exposure (63.3%). IF was disseminated in 55.6% of patients. Skin lesions was present in 58.3% of our patients, followed by pulmonary involvement in 55%, sinusitis in 21.7%, bone/joint involvement in 6.7% and 1 case each of endocarditis and brain abscess. Positive blood and skin biopsy cultures were detected in 60% and 48.3% of cases, respectively. Fusarium solani complex was the most commonly identified agent (66.6%). The majority of patients received monotherapy within the first 72 hours (71.6%), either with voriconazole or amphotericin B formulation. The mortality rates at 30, 60, and 90 days were 35%, 41.6%, and 45%, respectively. An important factor affecting mortality rates appears to be disseminated disease. The high percentage of patients with fungal involvement in multiple organs and systems highlights the need for extensive workup for additional sites of infection in severely immunocompromised children.

Immunogenicity and tolerability of a multicomponent meningococcal serogroup B (4CMenB) vaccine in healthy adolescents in Chile: a phase 2b/3 randomised, observer-blind, placebo-controlled study.

BACKGROUND: Effective glycoconjugate vaccines against Neisseria meningitidis serogroups A, C, W-135, and Y have been developed, but serogroup B remains a major cause of severe invasive disease in infants and adolescents worldwide. We assessed immunogenicity and tolerability of a four-component vaccine (4CMenB) in adolescents. METHODS: We did a randomised, observer-blind, placebo-controlled, study at 12 sites in Santiago and Valparaíso, Chile. Adolescents aged 11-17 years received one, two, or three doses of 4CMenB at 1 month, 2 month, or 6 month intervals. Immunogenicity was assessed as serum bactericidal activity using human complement (hSBA) against three reference strains for individual vaccine antigens, and assessed by ELISA against the fourth strain. Local and systemic reactions were recorded 7 days after each vaccination, and adverse events were monitored throughout the study. Participants were initially randomised to five groups (3:3:3:3:1) during the primary phase to receive either one dose, two doses 1 or 2 months apart, or three doses of 4CMenB, or three doses of placebo, with an additional three groups generated for the booster phase. All subjects received at least one dose of 4CMenB. Geometric mean titres, proportions of participants with serum bactericidal antibody titres of 4 or more, and Clopper-Pearson 95% CIs were calculated. The study is registered with ClinicalTrials.gov, number NCT00661713. FINDINGS: Overall, 1631 adolescents (mean age 13·8 [SD 1·9] years) received at least one dose of 4CMenB. After two or three doses, 99-100% of recipients had hSBA titres of 4 or more against test strains, compared with 92-97% after one dose (p<0·0145) and 29-50% after placebo. At 6 months 91-100% of participants still had titres of 4 or more for each strain after two or three doses, but only 73-76% after one dose; seroresponse rates reached 99-100% for each strain after second or third doses at 6 months. Local and systemic reaction rates were similar after each 4CMenB injection and did not increase with subsequent doses, but remained higher than placebo. No vaccine-related serious adverse events were reported and no significant safety signals were identified. INTERPRETATION: On the basis of immunogenicity responses this study provides evidence for an adolescent 4CMenB vaccine schedule of two doses, 1-6 months apart, to provide protection against meningococcal B infection. The extent of this protection against meningococcus B variants circulating worldwide will be determined by national surveys. FUNDING: Novartis Vaccines and Diagnostics.

Hypervirulent Strains of Neisseria meningitidis and Clinical Manifestations in Children With Invasive Meningococcal Disease.

BACKGROUND: Hypervirulent clonal complex (cc) have been associated with higher incidence and case fatality rate of invasive meningococcal disease (IMD). The aim of this study was to describe the clinical manifestations of the hypervirulent cc of meningococcus in children. METHODS: Retrospective study in patients hospitalized by IMD microbiologically confirmed at three children's tertiary health care centers in Santiago, Chile, between 2010 and 2018. Demographic, clinical information and determination of the cc and factor H binding protein (fHbp) alleles were performed. RESULTS: In total 93 cases were evaluated, sequence typing was available for 91 cases, and 87 (95.6%) had a cc assigned; 63.7% were MenW and 31.8% MenB. The median age was 9 months, 67% were male and 18.7% had any comorbidity. A 26.4% presented neurological deficit, 25.3% petechiae and 20% diarrhea. Sixty-seven percent were admitted to the pediatric intensive care unit (PICU) and the case fatality rate was 9.9%. Regarding cc and fHbp alleles, ST11, ST41/44 and allele 22 were the most frequently identified, with 63.7%, 19.8% and 72.5%, respectively. We found statistically significant differences between the cc and presence of petechiae, diagnosis of meningococcemia plus meningitis, admission and days in PICU and advanced support. Allele 22 for fHbp was associated with the absence of petechiae, low suspicion of IMD, less diagnosis of meningitis+meningococcemia, PICU admission, advanced support and adrenal insufficiency. CONCLUSION: Epidemiological and microbiological surveillance of IMD should integrate clinical and laboratory components, including molecular and genetic characterization, to enrich the dynamic understanding of the clinical evolution of IMD.

Clinical Outcome in Children With Cancer With Two or More Microorganisms Isolated From Blood Cultures During Episodes of Fever and Neutropenia.

BACKGROUND: Bacterial bloodstream infections are a major cause of morbidity and mortality in children with cancer and episodes of fever and neutropenia (FN). The aim of this study was to evaluate the clinical outcome in children with cancer with 2 or more microorganisms isolated from blood cultures during their episodes of FN. METHODS: Between 2016 and 2021, children presenting with high-risk FN, admitted to any of the 6 participating hospitals in Santiago, Chile, were included in this study if they have positive blood cultures. We compared the clinical outcome of children with 2 or more microorganisms versus those with single agent isolation. RESULTS: A total of 1074 episodes of high-risk FN were enrolled in the study period, of which 27% (298) had positive blood cultures and 3% (32) had 2 or more microorganisms isolated from blood cultures. The most frequent identified agents were Viridans group streptococci and Escherichia coli in 20%, followed by Coagulase negative staphylococci in 14%. Children with 2 or more microorganisms presented more days of fever (7 vs. 4 days, P = 0.02), needed longer courses of antimicrobial therapy (16 vs. 14 days, P = 0.04) and had higher mortality at day 30 (13% vs. 1%, P = 0.003). CONCLUSIONS: Children with cancer and FN with 2 or more microorganisms isolated from blood cultures had a worse clinical outcome than children with single agent isolation.

Usefulness of Peripheral Blood Cultures in Children With Cancer and Episodes of Fever and Neutropenia.

BACKGROUND: The collection of blood cultures (BC) is key for guiding antimicrobial therapy in children with febrile neutropenia (FN), more than 90% have central venous catheters (CVC). There is no consensus on the need for peripheral BC over central BC in this population. The aim of this study was to determine the contribution of peripheral BC over central BC in the diagnosis of bloodstream infections in children with FN. METHODS: Descriptive, retrospective study, episodes of FN recorded prospectively in 6 hospitals in Santiago, Chile, from 2016 to 2021. Central and peripheral BC were drawn upon admission. All episodes with at least one (+) BC were allocated to one of these groups: consistent (+) BC, inconsistent (+) BC, only CVC (+) BC and only peripheral (+) BC. The volume of the samples was recorded. RESULTS: The analysis included 241 episodes of FN with at least one (+) BC. The median age was 7.2 years, 51% were female, 84% had hematological cancer and 98% had episodes of high-risk FN. Of a total of 241 episodes, 135 (56%) had consistent (+) BC, 13 (5%) had inconsistent (+) BC, 35 (15%) had only CVC (+) BC and 58 (24%) had only peripheral (+) BC. There were no significant differences in the volume of the samples between central and peripheral BC. CONCLUSIONS: The proportion of bloodstream infections detected only through peripheral BC was 24%, higher than previously reported, not due to sample volume. We recommend obtaining peripheral as well CVC BC in children with FN.

[Voriconazole monitorization in pediatric patients, difficulties in dose adjustment]. / Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico.

We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.

[Respiratory viral infections during episodes of fever in children undergoing hematopoietic stem cell transplantation]. / Infecciones respiratorias virales en episodios de fiebre en niños con trasplante de precursores hematopoyéticos.

BACKGROUND: Children undergoing hematopoietic stem cell transplant (HSCT) can develop respiratory viral infections (RVI) during fever episodes. There are few data about clinical outcomes in RVI and compared to bacterial infections (BI) in this population. AIM: To determine clinical outcome of RVI, compared to BI in children with HSCT. METHODS: Prospective study, patients ≤ 18 years with cancer and HSCT admitted with fever at a National Bone Marrow Transplant Center (Hospital Calvo Mackenna), Chile, (April-2016 to May-2019). Clinical assessment, laboratory tests, blood cultures, nasopharyngeal sample for multiplex-PCR (Filmarray®), viral loads by PCR and cytokine panel (Luminex®, 38 cytokines) were performed. The following outcomes were evaluated: upper/lower respiratory tract disease (RTD), admission to ICU, mechanical ventilation, mortality and antimicrobial withdrawal. RESULTS: Of 56 febrile episodes, 35 (63%) were RVI, 12 (21%) BI and 9 (16%) with unknown etiology (UE). Median of age was 8.5 years, 62% male gender. Rhinovirus (54%) and coronavirus (15%) were the more frequent detected viruses. No significant differences in cytokine levels were observed between RVI and BI. 94% of RVI patients had symptomatic RTD, versus 33% in BI and 33% in UE group (p < 0.001), with lower-RTD in 69% of RVI group (p < 0,001). Admission to ICU was 11% in RVI, 17% in BI and 11% in UE group (p = 0.88); only 2 patients required mechanical ventilation (p = 0.37) and no mortality was reported. After an RVI was detected by PCR, antimicrobials were withdrawal in 26% of patients with RVI (p: 0.04). CONCLUSION: RVI are frequent etiologic agents in febrile episodes of patients with HSCT. Viral detection might help to rationalize the use of antimicrobials in this population.

[Clinical characteristics and microbiological profile of viridans group streptococci bacteremia in children with cancer and high-risk febrile neutropenia]. / Caracterización clínica y microbiológica de episodios de bacteriemia por Streptococcus grupo viridans en niños con cáncer y neutropenia febril de alto riesgo.

BACKGROUND: Viridans group streptococci (VGS) has acquired relevance as a microorganism causing febrile neutropenia, associated with significant morbidity. AIM: To characterize episodes of bacteremia caused by VGS in children with cancer who developed high-risk febrile neutropenia (HRFN) during the period from April 2004 to June 2018 in six pediatric hospitals of Santiago, Chile. METHOD: Database analysis of 4 successive, prospective and multicentric studies recording clinical and laboratory characteristics of patients, as well as antimicrobial susceptibility pattern of isolated strains. RESULTS: 95 episodes of VGS bacteremia in 91 children with HRFN were analyzed. It emphasizes acute myeloid leukemia as cancer type, deep neutropenia, prolonged hospitalization (15 days), with extended use of antimicrobials (14 days) and use of cytarabine in chemotherapy schemes (86% episodes). The most frequent clinical manifestations were respiratory and gastrointestinal, associating up to 26% viridans group shock syndrome. There was high resistance to ß lactams. As expected, there were not non-susceptible strains to vancomycin. DISCUSSION: VGS is a relevant microorganism in children with cancer, fever and neutropenia, with a high percentage of sepsis. Resistance to ß lactams is an issue that requires strict epidemiological surveillance in this population.

[Basic requirements of facilities for hospitals that treat hemato-oncological patients: hospital environment, diagnostic protocols and therapeutic arsenal]. / Parte I. Requerimientos básicos de infectología para hospitales que atienden pacientes hemato-oncológicos: ambiente hospitalario, protocolos diagnósticos y arsenal terapéutico. Fundamentación.

The care of cancer patients, including recipients of hematopoietic stem cell transplantation, has numerous challenges for hospitals that must provide safe environments in which exposure to pathogens that generate morbidity and mortality is reduced at maximum. At the same time, they must have established protocols that allow a rational study of the possible infectious etiologies and the existence of an adequate therapeutic arsenal together with timely treatment algorithms, updated according to consensus guidelines and effective according to the suspected or confirmed infection. This article introduces some of the arguments that support these requirements, then that are developed in three successive articles dedicated to the hospital environment, diagnostic protocols and therapeutic arsenal.

[Antimicrobial therapy in cancer patients and hematopoietic stem cell transplantation receptors]. / Parte IV. Terapia antimicrobiana en pacientes con cáncer y receptores de trasplante de precursores hematopoyéticos.

This manuscript includes the antiinfective therapeutic resources for immunocompromised patients under chemotherapy by cancer or hematopoietic stem cells transplant (HSCT) receptors. The document presents the antimicrobial therapy indicated in the most prevalent clinical situations in this population and the primary and alternative therapy for some specific microorganisms. The clinical situations included in the analysis are: febrile neutropenia without focus, sepsis, infections of the central nervous system, pneumonia, skin and soft tissue infections, neutropenic enterocolitis and urinary tract infection. The therapeutic resources, recommended doses and special precautions for the use of antimicrobial recommended in bacterial, viral, fungal and parasitic infections in this population are described, including the measurement of plasma concentrations of certain drugs in specific situations.

Antibody persistence and booster response in adolescents and young adults 4 and 7.5 years after immunization with 4CMenB vaccine.

BACKGROUND: Data on duration of protection against invasive meningococcal disease post-vaccination with the recombinant, 4-component, meningococcal serogroup B vaccine (4CMenB) are limited. We evaluated bactericidal activity persistence in adolescents/young adults up to 7.5 years post-primary vaccination with 4CMenB, and response to a booster dose compared with vaccine-naïve controls. METHODS: This open-label, multicenter study (NCT02446743) enrolled 15-24 year-old-previously vaccinated participants from Canada, Australia (group Primed_4y) 4 years post-priming with 4CMenB (2 doses; 0,1-month schedule), and Chile (Primed_7.5y) 7.5 years after priming with 4CMenB (2 doses; 0,1/0,2/0,6-month schedule) and vaccine-naïve participants of similar age (Naïve_4y and Naïve_7.5y groups). Primed participants received a booster dose; vaccine-naïve participants received 2 catch-up doses of 4CMenB, 1 month apart. We evaluated antibody persistence and immune responses using hSBA in terms of geometric mean titers and percentages of participants with hSBA titers ≥4, the kinetics of bactericidal activity post-booster (previously vaccinated) or post-2 doses (vaccine-naïve), and safety. RESULTS: Antibody levels declined at 4 (Primed_4y) and 7.5 (Primed_7.5y) years post-primary vaccination, but remained higher than in vaccine-naïve participants at baseline (≤44% vs ≤ 13% [fHbp]; ≤84% vs ≤ 24% [NadA]; ≤29% vs ≤ 14% [PorA]) for all vaccine antigens except NHBA (≤81% vs ≤ 79%). One month post-booster and post-second dose, 93-100% of primed and 79-100% of vaccine-naïve participants had hSBA titers ≥4 for all antigens. Kinetics of the antibody response were similar across groups with an early robust response observed 7 days post-booster/second dose. No vaccine-related serious adverse event was reported. CONCLUSION: For all antigens except NHBA, a higher proportion of primed participants had hSBA titers ≥4, at 4 and 7.5 years post-vaccination, compared with vaccine-naïve participants. A more robust immune response after booster compared to a first dose in vaccine-naïve individuals, showed effective priming in an adolescent/young adult population. No safety or new reactogenicity issues were identified.

Differential time to positivity and quantitative cultures for noninvasive diagnosis of catheter-related blood stream infection in children.

BACKGROUND: Accurate diagnosis of catheter-related blood stream infection (CRBSI) is necessary to make a decision about removal of the catheter. Differential time to positivity (DTP) and the ratio of quantitative cultures (RQC) between central and peripheral blood cultures have not been evaluated against a strict standard in children, namely catheter tip culture. OBJECTIVE: Our aim is to compare DTP and RQC in the diagnosis of catheter tip-confirmed catheter-related infection in children. METHOD: Prospective study performed in 2 large hospitals in Santiago, Chile. Children with clinically suspected CRBSI had 2 peripheral and central vein blood samples obtained for automated culture in Bact/Alert and for quantitative cultures in 5% sheep blood agar plate. The catheter tip was cultured. Sensitivity, specificity, positive predictive value, negative predictive value, likelihood ratios (LR), and accuracy of DTP and RQC were compared against catheter tip-confirmed CRBSI. RESULTS: During a 3-year period, 344 clinically suspected CRBSIs were diagnosed in children of which 124 episodes met study criteria. Catheter tip culture-confirmed CRBSI in 25 (20%) of 124 episodes. A total of 34 microorganisms were cultured from 25 CRBSI; 8 of 25 (32%) episodes were polymicrobial. Staphylococcus aureus followed by coagulase-negative Staphylococcus were the most common microorganisms. For CRBSI, DTP and RQC reached a sensitivity of 75% versus 24% (P < 0.001), specificity of 86 versus 94%, positive predictive value of 58% versus 50%, negative predictive value of 93% versus 82%, LR of 5.48 versus 4.50, and accuracy of 0.84 versus 0.79. CONCLUSIONS: In children, DTP was better than RQC for diagnosis of catheter tip-confirmed CRBSI.

Consenso de la Sociedad Chilena de Infectología para el manejo de episodios de neutropenia febril en adultos y niños con cáncer / Consensus of the Chilean Society of Infectious Diseases for the management of episodes of febrile neutropenia in adults and children with cancer

El Comité de Infecciones en Inmunocomprometidos de la Sociedad Chilena de Infectología presenta aquí una actualización en el Manejo de episodios de neutropenia febril en adultos y niños con cáncer, derivado de los grandes cambios ocurridos en los últimos años en el enfrentamiento de estos pacientes. Para estos efectos, un grupo multidisciplinario desarrolló recomendaciones en relación a: su enfrentamiento inicial, exámenes de laboratorio requeridos, el tratamiento antimicrobiano inicial empírico y frente a focos infecciosos conocidos, las infecciones fúngicas invasoras y profilaxis antimicrobiana.

The Committee of Infections in Immunocompromised Patients of the Chilean Society of Infectious Diseases presents an update in the Management of febrile neutropenia in adults and children with cancer. It comes from the significant changes that occurred in recent years in the confrontation of these patients. For which a multidisciplinary task force group developed recommendations in relation to their initial handling, laboratory exams required, the initial empirical antimicrobial treatment and in front of known infectious focus, invasive fungal infections and antimicrobial prophylaxis.

Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico / Voriconazole monitorization in pediatric patients, difficulties in dose adjustment

Resumen Presentamos el caso de un escolar de 10 años, con el diagnóstico de una recaída de una leucemia mieloide aguda que cursó con un episodio de una neutropenia febril de alto riesgo, posterior a un ciclo intensivo de quimioterapia, evolucionando con una infección fúngica invasora demostrada por histopatología. Se inició tratamiento con voriconazol intravenoso, evolucionando con concentraciones plasmáticas erráticas que requirieron sucesivos ajustes de dosis, lo que también ocurrió con la administración oral del medicamento. Finalmente, tuvo una respuesta favorable al tratamiento, a pesar de la dificultad de la dosificación para alcanzar niveles terapéuticos. La búsqueda activa y la terapia antifúngica anticipada, así como la monitorización seriada de concentraciones terapéuticas de voriconazol, permitieron un tratamiento antifúngico óptimo y oportuno, mejorando el pronóstico del paciente.

Abstract We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.

Penicillin resistance is not extrapolable to amoxicillin resistance in Streptococcus pneumoniae isolated from middle ear fluid in children with acute otitis media.

OBJECTIVES: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). METHODS: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). RESULTS: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). CONCLUSIONS: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.