Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 60
Filtrar
Mais filtros

Base de dados
País/Região como assunto
Tipo de documento
País de afiliação
Intervalo de ano de publicação
1.
Antimicrob Agents Chemother ; 68(10): e0086024, 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39194260

RESUMO

Intravenous ganciclovir and oral valganciclovir display significant variability in ganciclovir pharmacokinetics, particularly in children. Therapeutic drug monitoring currently relies on the area under the concentration-time (AUC). Machine-learning (ML) algorithms represent an interesting alternative to Maximum-a-Posteriori Bayesian-estimators for AUC estimation. The goal of our study was to develop and validate an ML-based limited sampling strategy (LSS) approach to determine ganciclovir AUC0-24 after administration of either intravenous ganciclovir or oral valganciclovir in children. Pharmacokinetic parameters from four published population pharmacokinetic models, in addition to the World Health Organization growth curve for children, were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles of children. Different ML algorithms were trained to predict AUC0-24 based on different combinations of two or three samples. Performances were evaluated in a simulated test set and in an external data set of real patients. The best estimation performances in the test set were obtained with the Xgboost algorithm using a 2 and 6 hours post dose LSS for oral valganciclovir (relative mean prediction error [rMPE] = 0.4% and relative root mean square error [rRMSE] = 5.7%) and 0 and 2 hours post dose LSS for intravenous ganciclovir (rMPE = 0.9% and rRMSE = 12.4%). In the external data set, the performance based on these two sample LSS was acceptable: rMPE = 0.2% and rRMSE = 16.5% for valganciclovir and rMPE = -9.7% and rRMSE = 17.2% for intravenous ganciclovir. The Xgboost algorithm developed resulted in a clinically relevant individual estimation using only two blood samples. This will improve the implementation of AUC-targeted ganciclovir therapeutic drug monitoring in children.


Assuntos
Antivirais , Área Sob a Curva , Monitoramento de Medicamentos , Ganciclovir , Aprendizado de Máquina , Valganciclovir , Humanos , Ganciclovir/farmacocinética , Ganciclovir/análogos & derivados , Valganciclovir/farmacocinética , Criança , Antivirais/farmacocinética , Antivirais/administração & dosagem , Monitoramento de Medicamentos/métodos , Pré-Escolar , Teorema de Bayes , Algoritmos , Administração Oral , Masculino , Feminino , Infecções por Citomegalovirus/tratamento farmacológico , Lactente , Administração Intravenosa , Adolescente
2.
Br J Clin Pharmacol ; 87(8): 3105-3114, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33373493

RESUMO

AIMS: Ganciclovir (GCV) and its prodrug valganciclovir (VGCV) are first-line agents to prevent and treat cytomegalovirus in transplant recipients. There is high pharmacokinetic (PK) interindividual variability and PK data are scarce, especially in paediatric stem cell transplant (SCT) recipients. We sought to determine the optimal GCV and VGCV dosing in transplanted children. METHODS: We conducted a single-centre retrospective population PK (POPPK) study of IV GCV and enteral VGCV in paediatric solid organ transplant (SOT) and SCT recipients. We included children who were transplanted and had available plasma GCV concentrations, done per standard of care. POPPK analysis was performed using a nonlinear mixed effects modelling approach with NONMEM. Optimal dosing was determined based on the achievement of the surrogate efficacy target: GCV 24 h area under the concentration-time curve (AUC0-24h ) of 40-60 mg.h.L-1 . RESULTS: Fifty children with a median [range] age of 7.5 years [0.5-17.4] contributed 580 PK samples. A two-compartment model with first-order absorption with a lag time and first-order elimination fit the data well. Creatinine clearance and body weight (WT) were significant covariates for GCV clearance (CL); and WT for the volumes of distribution. IV GCV 15-20 mg.kg-1 .day-1 divided every 12 hours achieved the highest probability of target achievement (PTA) (33.0-33.8%). Enteral VGCV 30 and 40 mg.kg-1 .day-1 divided every 12 hours in children 0-<6 years, and 6-18 years, respectively, achieved the highest PTA (29.1-33.0%). CONCLUSION: This is the first POPPK model developed in children with either SOT or SCT. Concentration target achievement was low, suggesting a potential benefit for therapeutic drug monitoring to ensure optimal exposure.


Assuntos
Ganciclovir , Transplantados , Antivirais , Criança , Humanos , Estudos Retrospectivos , Transplante de Células-Tronco , Valganciclovir
3.
Pediatr Blood Cancer ; 68(6): e28944, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33773013

RESUMO

BACKGROUND: Children treated for acute lymphoblastic leukemia (ALL) are at high risk of invasive pneumococcal disease (IPD). We assessed immunity to S. pneumoniae among children after ALL treatment, and the impact of pneumococcal immunization during and after chemotherapy. METHODS: We performed an observational retrospective study of children treated for ALL at a single center. All children were fully immunized with three routine doses of pneumococcal conjugate vaccine (PCV) prior to ALL diagnosis. Children from Group 1 received a 13-valent PCV (PCV13) dose during the maintenance phase as well as a PCV13 booster after completing chemotherapy, while Group 2 only received the postchemotherapy dose. Serologic testing was performed after chemotherapy and again after the postchemotherapy dose. A serotype-specific antibody level ≥0.35 µg/ml was considered protective, and patients with protective levels for ≥70% of serotypes in the PCV7 vaccine were defined as seroprotected. RESULTS: A total of 71 children (median age 46 months, range 12-160) were included. At the end of chemotherapy, 53.1% of children in Group 1 (17/32) and 25.6% in Group 2 (10/39) were seroprotected (p = .018). After the postchemotherapy booster, seroprotection rates increased to 96.9% in Group 1 (31/32) and 100% in Group 2. CONCLUSIONS: Rates of pneumococcal seroprotection among children with ALL are low following chemotherapy, despite prior routine immunization. A PCV booster during chemotherapy may shorten the period of susceptibility to IPD in some children. However, irrespective of a booster during chemotherapy, a PCV dose postchemotherapy appears sufficient to confer high rates of seroprotection against IPD.


Assuntos
Infecções Pneumocócicas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Criança , Vacina Pneumocócica Conjugada Heptavalente , Humanos , Lactente , Infecções Pneumocócicas/prevenção & controle , Vacinas Pneumocócicas , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Streptococcus pneumoniae , Vacinação , Vacinas Conjugadas
4.
J Pediatr Hematol Oncol ; 42(6): 410-411, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32496444

RESUMO

Liver abscesses are poorly known in sickle cell disease. We report here multiple liver abscesses occurring in a 17-year-old patient with hemoglobin SC disease. A Fusobacterium nucleatum was identified on cyst puncture. Such complications have been described in only 11 children and young adults with hemoglobin SS/Sß-thalassemia diseases. Fusobacterium species are the most frequent pathogens reported and require anaerobic culture to be identified.


Assuntos
Infecções por Fusobacterium/complicações , Fusobacterium nucleatum/isolamento & purificação , Doença da Hemoglobina SC/microbiologia , Abscesso Hepático/complicações , Adolescente , Antibacterianos/uso terapêutico , Infecções por Fusobacterium/microbiologia , Doença da Hemoglobina SC/patologia , Humanos , Abscesso Hepático/microbiologia , Masculino , Prognóstico
5.
Pediatr Blood Cancer ; 64(2): 315-320, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27718310

RESUMO

BACKGROUND: The objective of this retrospective study was to assess protection against vaccine preventable diseases (VPDs) in children treated for acute lymphoblastic leukemia (ALL). PROCEDURE: Clinical characteristics and vaccination records were collected. Antibodies against VPDs were measured after completion of chemotherapy and after a booster dose of vaccine. Immunization status of household members was evaluated. RESULTS: Sixty children were included. Median interval between the end of chemotherapy and enrolment in the study was 13 months (range 1-145). At ALL diagnosis, 81.3% of the children were up to date with their vaccination schedule. This proportion decreased to 52.9% at enrolment. Among the parents, 21% were up to date with their immunization schedule and 42% had received seasonal influenza vaccination. After chemotherapy, less than 50% of the patients were seroprotected against tetanus, diphtheria, polio 3, Haemophilus influenzae type b (Hib), and mumps and no more than 80% were seroprotected against polio 1 and 2, measles, rubella, and varicella. After a booster dose of vaccine, the rate of protection increased to over 90% for each of the following antigens: TT, DT, polio 1, Hib, measles, and rubella. Nevertheless, polio 3, mumps, and varicella-zoster virus antibodies titers/concentrations remained below seroprotective thresholds in over 20% of the patients. CONCLUSIONS: After chemotherapy for ALL, most of the children were not protected against VPDs. As the majority mounted a robust response to booster vaccines, efforts need to be done to improve protection against VPDs by implementing a systematic vaccine booster schedule. This could also be helped by reinforcing household members' immunization.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Infecções Bacterianas/prevenção & controle , Imunização Secundária/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Vacinas/uso terapêutico , Viroses/prevenção & controle , Adolescente , Anticorpos Antivirais/sangue , Infecções Bacterianas/imunologia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Esquemas de Imunização , Lactente , Masculino , Estadiamento de Neoplasias , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico , Estudos Retrospectivos , Vacinas/imunologia , Viroses/imunologia
6.
Clin Infect Dis ; 62(1): 75-7, 2016 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-26409062

RESUMO

Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly.


Assuntos
Vacina contra Varicela , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes , Criança , Pré-Escolar , Fasciite Necrosante , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos
7.
Fetal Diagn Ther ; 39(1): 74-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-25138225

RESUMO

An increased prevalence of syphilis has been observed in many developed countries over the last decade. During pregnancy, syphilis can affect the fetus through development of nonspecific symptoms such as microcephaly, ascites, hepatosplenomegaly, dilated and echogenic bowel, placentomegaly, and, uncommonly, fetal hydrops. Congenital syphilis also leads to hematologic abnormalities such as anemia, thrombocytopenia, leukopenia, and leukocytosis. We present a case of nonimmune fetal hydrops with anemia related to syphilis infection. Diagnosis was confirmed by a maternal serological test and microbiological testing on amniotic fluid, umbilical cord, and placental tissues. The patient was treated with penicillin and the fetus received an intrauterine red blood cell transfusion, but fetal death occurred shortly after. Such a presentation is mostly related to parvovirus B19, and syphilis etiology is poorly mentioned because physicians have rarely seen early congenital syphilis in the past. However, given the increasing prevalence of this disease in the adult population, clinicians should remain alert to the various presentations of congenital syphilis.


Assuntos
Anemia/complicações , Hidropisia Fetal/microbiologia , Complicações Infecciosas na Gravidez/microbiologia , Sífilis Congênita/complicações , Feminino , Humanos , Gravidez , Adulto Jovem
9.
J Immunol ; 189(10): 5016-28, 2012 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-23034171

RESUMO

CMV and varicella zoster virus (VZV) are significant causes of morbidity and mortality following umbilical cord blood transplantation (UCBT). However, the kinetics of reconstitution and protective potential of antiviral cell-mediated immune responses following UCBT remain poorly characterized. In this study, the reconstitution of CMV- and VZV-specific T cell responses was assessed using IFN-γ ELISPOT in 28 children who underwent UCBT to treat hematological or inherited disorders. Barely detectable in the first 3 mo posttransplantation, CMV- and VZV-specific T cell responses were observed in 30.4% and 40.3% of study subjects after 36 mo of follow-up. Four of five CMV-seropositive subjects developed detectable levels of circulating CMV DNA (DNAemia), and 5 of 17 VZV-seropositive patients experienced herpes zoster during the posttransplant period. Four CMV-seronegative subjects developed IFN-γ responses against CMV, and four subjects developed a VZV-specific IFN-γ response without clinical signs of infection. No CMV- or VZV-related events were observed in study subjects following the development of CMV- or VZV-specific responses > 150 spot-forming units/10(6) PBMCs, consistent with T cell-mediated protection. Finally, famciclovir prophylaxis did not strictly prevent the reconstitution of the VZV-specific T cell repertoire, because the frequency of T cells producing IFN-γ in response to VZV Ags reached levels consistent with protection in two nonzoster subjects. Monitoring of CMV- and VZV-specific cell-mediated immunity could inform immunocompetence and guide the initiation and cessation of antiherpetic prophylaxis in UCBT recipients.


Assuntos
Varicela/imunologia , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Herpesvirus Humano 3/imunologia , Recuperação de Função Fisiológica/imunologia , Linfócitos T/imunologia , Adolescente , Adulto , Criança , Pré-Escolar , ELISPOT/métodos , Feminino , Seguimentos , Doenças Genéticas Inatas/imunologia , Doenças Genéticas Inatas/terapia , Doenças Hematológicas/imunologia , Doenças Hematológicas/terapia , Humanos , Lactente , Interferon gama/imunologia , Masculino , Transplante Homólogo
10.
J Pediatr Hematol Oncol ; 36(5): e319-21, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24977404

RESUMO

Posttransplant lymphoproliferative disease (PTLD) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. We describe here the case of a boy with history of induction failure of a T-cell acute lymphoblastic leukemia, who presented a life-threatening situation of nonengraftment and rituximab-refractory PTLD after the first hematopoietic stem cell transplantation. We decided to use an unusual strategy of combining a nonmyeloablative conditioning (fludarabine and cyclophosphamide) with a calcineurin inhibitor-free GvHD prophylaxis (sirolimus and mycophenolate mofetil). This strategy had permitted the control of an Epstein-Barr virus PLTD in umbilical cord blood transplantation without further reactivation.


Assuntos
Anticorpos Monoclonais Murinos/farmacologia , Calcineurina , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/terapia , Ácido Micofenólico/análogos & derivados , Leucemia-Linfoma Linfoblástico de Células T Precursoras/complicações , Sirolimo/uso terapêutico , Antineoplásicos/farmacologia , Criança , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Humanos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/etiologia , Masculino , Ácido Micofenólico/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células T Precursoras/terapia , Prognóstico , Rituximab , Condicionamento Pré-Transplante , Transplante Homólogo , Vidarabina/análogos & derivados , Vidarabina/uso terapêutico
11.
Can J Infect Dis Med Microbiol ; 25(6): 327-43, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25587296

RESUMO

Invasive fungal infections cause significant morbidity and mortality in patients with concomitant underlying immunosuppressive diseases. The recent addition of new triazoles to the antifungal armamentarium has allowed for extended-spectrum activity and flexibility of administration. Over the years, clinical use has raised concerns about the degree of drug exposure following standard approved drug dosing, questioning the need for therapeutic drug monitoring (TDM). Accordingly, the present guidelines focus on TDM of triazole antifungal agents. A review of the rationale for triazole TDM, the targeted patient populations and available laboratory methods, as well as practical recommendations based on current evidence from an extended literature review are provided in the present document.


Les infections fongiques invasives sont responsables d'une morbidité et d'une mortalité importantes chez les patients atteints d'une maladie immunodépressive. L'ajout des nouveaux triazoles aux traitements antifongiques a élargi le spectre d'activité et la flexibilité d'administration. Au fil des ans, leur utilisation clinique a suscité des inquiétudes quant au degré d'exposition au médicament selon une posologie approuvée standard, ce qui soulève la nécessité de la pharmacovigilance thérapeutique (PVT). Les présentes lignes directrices portent donc sur la PVT des antifongiques triazolés. Dans le présent document sont exposées une analyse de la raison d'être de la PVT des triazoles, les populations de patients ciblées et les méthodes de laboratoire offertes, de même que des recommandations pratiques fondées sur des données probantes à jour tirées d'une analyse bibliographique approfondie.

12.
J Perinatol ; 44(5): 731-738, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38553603

RESUMO

BACKGROUND AND OBJECTIVES: Data on urinary tract infections (UTIs) in very preterm neonates (VPTNs) are scarce. We aimed to (i) describe the characteristics of UTIs in VPTNs and (ii) compare the diagnostic practices of neonatal clinicians to established pediatric guidelines. METHODS: All VPTNs (<29 weeks GA) with a suspected UTI at the CHU Sainte-Justine neonatal intensive care unit from January 1, 2014, and December 31, 2019, were included and divided into two definition categories: Possible UTI, and Definite UTI. RESULTS: Most episodes were Possible UTI (87%). Symptoms of UTIs and pathogens varied based on the definition category. A positive urinalysis was obtained in 25%. Possible UTI episodes grew 2 organisms in 62% of cases and <50,000 CFU/mL in 62% of cases. CONCLUSION: Characteristics of UTIs in VPTNs vary based on the definition category and case definitions used by clinicians differ from that of established pediatric guidelines.


Assuntos
Unidades de Terapia Intensiva Neonatal , Infecções Urinárias , Humanos , Infecções Urinárias/diagnóstico , Recém-Nascido , Feminino , Masculino , Estudos Retrospectivos , Lactente Extremamente Prematuro , Doenças do Prematuro/diagnóstico , Idade Gestacional , Guias de Prática Clínica como Assunto , Recém-Nascido Prematuro , Urinálise
13.
Clin Pharmacokinet ; 63(4): 539-550, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38492206

RESUMO

BACKGROUND AND OBJECTIVES: Ganciclovir (GCV) and valganciclovir (VGCV) show large interindividual pharmacokinetic variability, particularly in children. The objectives of this study were (1) to develop machine learning (ML) algorithms trained on simulated pharmacokinetics profiles obtained by Monte Carlo simulations to estimate the best ganciclovir or valganciclovir starting dose in children and (2) to compare its performances on real-world profiles to previously published equation derived from literature population pharmacokinetic (POPPK) models achieving about 20% of profiles within the target. MATERIALS AND METHODS: The pharmacokinetic parameters of four literature POPPK models in addition to the World Health Organization (WHO) growth curve for children were used in the mrgsolve R package to simulate 10,800 pharmacokinetic profiles. ML algorithms were developed and benchmarked to predict the probability to reach the steady-state, area-under-the-curve target (AUC0-24 within 40-60 mg × h/L) based on demographic characteristics only. The best ML algorithm was then used to calculate the starting dose maximizing the target attainment. Performances were evaluated for ML and literature formula in a test set and in an external set of 32 and 31 actual patients (GCV and VGCV, respectively). RESULTS: A combination of Xgboost, neural network, and random forest algorithms yielded the best performances and highest target attainment in the test set (36.8% for GCV and 35.3% for the VGCV). In actual patients, the best GCV ML starting dose yielded the highest target attainment rate (25.8%) and performed equally for VGCV with the Franck model formula (35.3% for both). CONCLUSION: The ML algorithms exhibit good performances in comparison with previously validated models and should be evaluated prospectively.


Assuntos
Antivirais , Ganciclovir , Aprendizado de Máquina , Método de Monte Carlo , Valganciclovir , Humanos , Ganciclovir/farmacocinética , Ganciclovir/administração & dosagem , Ganciclovir/análogos & derivados , Valganciclovir/farmacocinética , Valganciclovir/administração & dosagem , Criança , Antivirais/farmacocinética , Antivirais/administração & dosagem , Pré-Escolar , Masculino , Feminino , Adolescente , Lactente , Modelos Biológicos , Algoritmos , Área Sob a Curva , Simulação por Computador
14.
Paediatr Child Health ; 18(6): 311-6, 2013 Jun.
Artigo em Inglês, Francês | MEDLINE | ID: mdl-24421702

RESUMO

Azithromycin is an antibiotic that is commonly prescribed for upper and lower respiratory tract infections in children. While it has proven benefits, some concerns regarding azithromycin use have arisen in recent years. This practice point considers azithromycin therapy for acute respiratory infections in otherwise healthy children. Pharmacokinetics, spectrum of activity, the problem of resistant bacteria and clinical aspects are considered, along with recommendations for use and contraindications. Azithromycin should be avoided in patients with a significant risk of bacteremia. It is associated with pneumococcal resistance and, with stated exceptions, is generally not recommended for the treatment of acute pharyngitis, acute otitis media or pneumococcal community-acquired pneumonia in the paediatric population.


L'azithromycine est un antibiotique souvent prescrit chez les enfants en présence d'infections des voies respiratoires supérieures et inférieures. Elle a des avantages démontrés, mais plusieurs préoccupations ont surgi ces dernières années au sujet de son utilisation. Le présent point de pratique permet d'évaluer le traitement d'infections respiratoires aiguës à l'azithromycine chez des enfants autrement en santé. La pharmacocinétique, le spectre d'activités, le problème de bactéries résistantes et les aspects cliniques sont évalués, de même que les recommandations relatives à l'utilisation et les contre-indications. Il faudrait éviter l'azithromycine chez les patients présentant un risque marqué de bactériémie. Ce médicament s'associe à une résistance pneumococcique et, sauf dans des exceptions définies, il n'est généralement pas recommandé pour traiter la pharyngite aiguë, l'otite moyenne aiguë ou la pneumonie pneumococcique d'origine non nosocomiale au sein de la population d'âge pédiatrique.

15.
Can J Infect Dis Med Microbiol ; 24(1): e11-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24421794

RESUMO

BACKGROUND: Pediatric data regarding cytomegalovirus (CMV) infections in pediatric patients receiving umbilical cord blood (UCB) transplantation are sparse. OBJECTIVE: To determine whether UCB transplantation increases the risk of CMV infection and disease compared with other graft sources. METHODS: The medical files of patients who underwent allogeneic hematopoietic stem cell transplantation at CHU Ste-Justine (Montreal, Quebec) from April 2000 to December 2006 were retrospectively reviewed. A Cox proportional hazard model was used to assess the effect of potential predictors of outcomes. RESULTS: A total of 176 patients with a median age of nine years (range 0.1 to 18 years) underwent hematopoietic stem cell transplantation. The source of stem cells were UCB, bone marrow and peripheral blood stem cells in 86, 86 and four of the cases, respectively. CMV infection occurred in 29 patients (16%). At day 100 post-transplantation, the rate of CMV infection was 13% in UCB transplant recipients (11 of 86) versus 20% in those with other sources of graft (18 of 90) (P=0.19). Positive CMV serology of the recipient and leukocyte depletion were two independent variables associated with an increased risk of CMV infection. Among infected patients, six developed CMV disease (20.7%). The rate of CMV disease one year after infection was 49% in patients who received UCB (five of 11) and 6% in others (one of 18). This difference was significant by univariate (P=0.01) but not by multivariate analysis. CONCLUSION: In the setting of the current study, with a moderate CMV infection rate (16.5%), UCB transplantation did not appear to increase the risk of CMV infection and disease.


HISTORIQUE: Il existe peu de données pédiatriques sur les infections à cytomégalovirus (CMV) chez les patients pédiatriques qui reçoivent une greffe de sang du cordon ombilical (SCO). OBJECTIF: Déterminer si la greffe de SCO accroît le risque d'infection à CMV par rapport à d'autres greffes. MÉTHODOLOGIE: Les chercheurs ont procédé à une analyse rétrospective des dossiers médicaux de patients qui ont subi une greffe de cellules souches hématopoïétiques au CHU Sainte-Justine de Montréal, au Québec, entre avril 2000 et décembre 2006. Ils ont utilisé un modèle de risque proportionnel de Cox pour évaluer l'effet des prédicteurs potentiels d'issues. RÉSULTATS: Au total, 176 patients ayant un âge médian de neuf ans (plage de 0,1 à 18 ans) ont subi une greffe de cellules souches hématopoïétiques. Les cellules souches provenaient du SCO, de la moelle épinière et du sang périphérique dans 86, 86 et quatre cas, respectivement. Une infection à CMV s'est manifestée chez 29 patients (16 %). Au 100e jour après la greffe, le taux d'infection à CMV s'élevait à 13 % chez les greffés de SCO (11 sur 86) par rapport à 20 % chez ceux dont la greffe provenait d'autres sources (18 sur 90) (P=0,19). La sérologie positive au CMV du receveur et la déplétion leucocytaire étaient deux variables indépendantes associées à un risque plus élevé d'infection à CMV. Chez les patients infectés, six ont contracté la maladie à CMV (20,7 %). Le taux de maladie à CMV un an après l'infection s'élevait à 49 % chez les patients qui avaient reçu du SCO (cinq sur 11) et 6 % chez les autres (un sur 18). Cette différence était significative selon l'analyse univariée (P=0,01), mais pas selon l'analyse multivariée. CONCLUSION: Dans le cadre de la présente étude, où le taux d'infection à CMV était modéré (16,5 %), la greffe de SCO ne semblait pas accroître le risque d'infection et de maladie à CMV.

16.
J Pediatr Pharmacol Ther ; 28(1): 93-101, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36777981

RESUMO

Congenitally acquired cytomegalovirus (CMV) infection is the most prevalent congenital infection worldwide and the most frequent cause of acquired sensorineural hearing loss. The burden of the disease is even more important in premature and very low birth weight infants. However, few data exist on the treatment with intravenous ganciclovir and oral valganciclovir in this vulnerable population. We report the case of twins congenitally infected with CMV and born prematurely at 27 weeks' gestation. Treatment regimens were initially individualized for their prematurity and renal function, and then adjusted with therapeutic drug monitoring (TDM) to adapt to their continuously evolving physiologic maturation. As infants were aging, the plasmatic half-life of ganciclovir slowly decreased to term infant values around 10 weeks of chronological age, or 37 weeks of postmenstrual age. Results for blood polymerase chain reaction tests became negative and long-term follow-ups were satisfactory in both twins. The limited data for infants born before 32 weeks of gestation or at less than 1200 g and evolution of ganciclovir pharmacokinetic parameters justify the use of TDM in these settings.

18.
Clin Pharmacol Ther ; 112(2): 233-276, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-34596243

RESUMO

Ganciclovir and valganciclovir are first choice drugs for the prevention and treatment of cytomegalovirus infection and disease in solid organ and stem cell transplant recipients. Only a few studies on the pharmacokinetics and exposure/efficacy or exposure/safety relationships of ganciclovir and valganciclovir in transplant recipients have been published so far, and there are still controversies about the exposure parameter to use for therapeutic drug monitoring (TDM). We performed an extensive literature review of the clinical pharmacokinetics data, the exposure/effect relationships in terms of efficacy and safety, and the available tools for valganciclovir and ganciclovir TDM in adults and pediatrics transplant recipients. The pharmacokinetics of ganciclovir and valganciclovir is well described in adults and children, and a high interindividual variability is commonly observed. In contrast, the drug pharmacodynamics has been poorly described in adults and barely in children. The average 24-hour area under the concentration-time curve (AUC0-24h ) seems to be the best predictor of efficacy and toxicity. The benefit of TDM remains controversial in adult patients but should be considered in children due to higher interindividual variability and lower probability of target attainment. Several bayesian estimators based on limited sampling strategies have been developed with this aim and may be used in clinical practice for the AUC-based individual dose adjustment of ganciclovir and valganciclovir.


Assuntos
Ganciclovir , Transplante de Órgãos , Adulto , Antivirais/farmacocinética , Teorema de Bayes , Criança , Monitoramento de Medicamentos , Ganciclovir/efeitos adversos , Ganciclovir/farmacocinética , Humanos , Valganciclovir
19.
Can J Hosp Pharm ; 75(3): 201-209, 2022.
Artigo em Francês | MEDLINE | ID: mdl-35847460

RESUMO

Background: The emergence of antibiotic resistance has contributed to the development of multidrug-resistant bacteria, which is a major concern. Objectives: The primary objective was to explore the possible association between antibiotic use and the emergence of resistance in a mother-child university hospital. Method: This retrospective study was conducted in a university hospital centre. Antibiotic-bacteria pairs were established, taking into account the number of isolates, actual antibiotic use, and clinical relevance. For each pair, a comparison of 2 variables (antibiotic utilization and rate of resistance) was quantified with the Pearson coefficient. Three analyses were conducted: no lag between utilization and resistance, 1-year lag, and 2-year lag. Results: Thirty antibiotic-bacteria pairs were selected from hematology-oncology and 18 from neonatology. In hematology-oncology, 6 pairs had a positive correlation (Pearson coefficient > 0.7): 2 pairs involving meropenem, 2 involving ceftazidime, and 2 involving piperacillin-tazobactam. In 3 of these cases, there was no lag between consumption of antibiotics and presence of resistance. In neonatology, 3 antibiotic-bacteria pairs had a positive correlation, 1 each involving vancomycin, cloxacillin, and meropenem. Conclusions: It is possible to explore the potential association between consumption of antibiotics and emergence of resistance in a particular centre. Our exploratory approach was based on manual data processing. It would be interesting to consider a continuous systematic approach, allowing automatic generation of correlations.

20.
JGH Open ; 6(9): 625-629, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36091316

RESUMO

Background and Aim: Patients with inflammatory bowel disease (IBD) are at increased risk for life-threatening complications of Epstein-Barr virus (EBV), including lymphoproliferative diseases. These complications are likely related to inherent immune dysfunction and immunomodulating therapies often used. We aimed to determine the seroprevalence of EBV at diagnosis in our population, its impact on disease at onset, and the risk of active EBV infection. Methods: We included patients newly diagnosed with IBD for whom an EBV serology was performed over a 2-year period. Demographic information and data on disease characteristics were collected retrospectively. Stored serum from the time of diagnosis was retrieved when available for the patients with positive EBV serology, and quantitative polymerase chain reaction testing was performed to assess the pre-treatment viral load of EBV. Results: One hundred twenty patients were included in the study. Fifty-three patients (44.2%) had positive EBV serology at diagnosis. Stratified by age group, the prevalence of seropositive patients was for 0 to <10 years 35%, 10 to <17 years 46%, and ≥17 years 50%. Overall, therapies started within 6 months of diagnosis were similar in both the seropositive and seronegative groups. Within the seropositive group, 66% received systemic corticosteroids, 32.1% infliximab, 5.7% adalimumab, and 5.7% azathioprine. Conclusion: EBV seroprevalence is high in pediatric patients with IBD. EBV seropositivity did not seem to influence the severity of disease at onset or initial choice of therapy.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA