@article {7743, title = {Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation.}, journal = {J Antimicrob Chemother}, volume = {70}, year = {2015}, month = {2015 Jan}, pages = {198-206}, abstract = {

OBJECTIVES: To report on linezolid exposure in a paediatric population who routinely underwent therapeutic drug monitoring (TDM) for dosage optimization and to assess the factors affecting interpatient variability.

METHODS: We performed a retrospective study of patients whose plasma C(min) and Cmax levels were measured during linezolid treatment. Adequate exposure was defined as a C(min) of 2-7 mg/L and/or an estimated AUC24 of 160-300 mg {\textperiodcentered} h/L. Patients were divided into two subgroups (Group 1, 2-11 years; Group 2, 12-18 years). Monte Carlo simulation was performed to investigate whether or not the currently recommended dosages might enable a high probability of target attainment (PTA) of two thresholds for linezolid efficacy (AUC24/MIC >= 80 or >= 100). Data on demographic characteristics, disease, microbiology and haematochemical parameters and outcomes were collected.

RESULTS: A total of 23 patients were included. Standard dosages were suboptimal in 50.0\% and 44.4\% of patients in Group 1 and Group 2, respectively. Among those who underwent multiple instances of TDM, the dosages were increased in 33.3\% of cases in both groups, and decreased in 6.6\% and 9.5\% of cases in Group 1 and Group 2, respectively. Co-treatment with phenobarbital, proton pump inhibitors and amiodarone accounted for most of the variability in C(min) (adjusted R(2) of 0.692). Simulations showed a PTA of >= 90\% with the current dosing regimens in both groups only for pathogens with an MIC <= 1 mg/L.

CONCLUSIONS: Higher dosages of linezolid may be needed, especially in Group 1 when in the presence of pathogens with an MIC >1 mg/L. The role of TDM should be encouraged for optimization of linezolid exposure in the paediatric setting in the presence of infections caused by pathogens with borderline susceptibility and/or for patients co-treated with drugs that may alter linezolid exposure.

}, keywords = {Acetamides, Anti-Bacterial Agents, Area Under Curve, Child, Child, Preschool, Drug Monitoring, Female, Gram-Positive Bacterial Infections, Hospitalization, Humans, Infant, Inpatients, Linezolid, Male, Monte Carlo Method, Oxazolidinones, Plasma, Retrospective Studies, Tertiary Care Centers}, issn = {1460-2091}, doi = {10.1093/jac/dku337}, author = {Cojutti, Piergiorgio and Maximova, Natalia and Crichiutti, Giovanni and Isola, Miriam and Pea, Federico} } @article {3613, title = {Long-term follow-up in children with benign convulsions associated with gastroenteritis.}, journal = {Eur J Paediatr Neurol}, volume = {18}, year = {2014}, month = {2014 Sep}, pages = {572-7}, abstract = {

BACKGROUND: The outcome of benign convulsions associated with gastroenteritis (CwG) has generally been reported as being excellent. However, these data need to be confirmed in studies with longer follow-up evaluations.

AIM: To assess the long-term neurological outcome of a large sample of children presenting with CwG.

METHODS: We reviewed clinical features of 81 subjects presenting with CwG (1994-2010) from three different Italian centers with a follow-up period of at least 3 years.

RESULTS: Follow-up period ranged from 39 months to 15 years (mean 9.8 years). Neurological examination and cognitive level at the last evaluation were normal in all the patients. A mild attention deficit was detected in three cases (3.7\%). Fourteen children (17.3\%) received chronic anti-epileptic therapy. Interictal EEG abnormalities detected at onset in 20 patients (24.7\%) reverted to normal. Transient EEG epileptiform abnormalities were detected in other three cases (3.7\%), and a transient photosensitivity in one (1.2\%). No recurrence of CwG was observed. Three patients (3.7\%) presented with a febrile seizure and two (2.5\%) with an unprovoked seizure, but none developed epilepsy.

CONCLUSIONS: The long-term evaluation of children with CwG confirms the excellent prognosis of this condition, with normal psychomotor development and low risk of relapse and of subsequent epilepsy.

}, keywords = {Adolescent, Anticonvulsants, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Electroencephalography, Epilepsy, Female, Gastroenteritis, Humans, Longitudinal Studies, Male, Neurologic Examination, Retrospective Studies}, issn = {1532-2130}, doi = {10.1016/j.ejpn.2014.04.006}, author = {Verrotti, Alberto and Moavero, Romina and Vigevano, Federico and Cantonetti, Laura and Guerra, Azzurra and Spezia, Elisabetta and Tricarico, Antonella and Nanni, Giuliana and Agostinelli, Sergio and Chiarelli, Francesco and Parisi, Pasquale and Capovilla, Giuseppe and Beccaria, Francesca and Spalice, Alberto and Coppola, Giangennaro and Franzoni, Emilio and Gentile, Valentina and Casellato, Susanna and Veggiotti, Pierangelo and Malgesini, Sara and Crichiutti, Giovanni and Balestri, Paolo and Grosso, Salvatore and Zamponi, Nelia and Incorpora, Gemma and Savasta, Salvatore and Costa, Paola and Pruna, Dario and Cusmai, Raffaella} }