TY - JOUR T1 - Pharmacokinetic/pharmacodynamic evaluation of linezolid in hospitalized paediatric patients: a step toward dose optimization by means of therapeutic drug monitoring and Monte Carlo simulation. JF - J Antimicrob Chemother Y1 - 2015 A1 - Cojutti, Piergiorgio A1 - Maximova, Natalia A1 - Crichiutti, Giovanni A1 - Isola, Miriam A1 - Pea, Federico KW - Acetamides KW - Anti-Bacterial Agents KW - Area Under Curve KW - Child KW - Child, Preschool KW - Drug Monitoring KW - Female KW - Gram-Positive Bacterial Infections KW - Hospitalization KW - Humans KW - Infant KW - Inpatients KW - Linezolid KW - Male KW - Monte Carlo Method KW - Oxazolidinones KW - Plasma KW - Retrospective Studies KW - Tertiary Care Centers AB -

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 · 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.

VL - 70 IS - 1 U1 - http://www.ncbi.nlm.nih.gov/pubmed/25182066?dopt=Abstract ER - TY - JOUR T1 - Long-term follow-up in children with benign convulsions associated with gastroenteritis. JF - Eur J Paediatr Neurol Y1 - 2014 A1 - Verrotti, Alberto A1 - Moavero, Romina A1 - Vigevano, Federico A1 - Cantonetti, Laura A1 - Guerra, Azzurra A1 - Spezia, Elisabetta A1 - Tricarico, Antonella A1 - Nanni, Giuliana A1 - Agostinelli, Sergio A1 - Chiarelli, Francesco A1 - Parisi, Pasquale A1 - Capovilla, Giuseppe A1 - Beccaria, Francesca A1 - Spalice, Alberto A1 - Coppola, Giangennaro A1 - Franzoni, Emilio A1 - Gentile, Valentina A1 - Casellato, Susanna A1 - Veggiotti, Pierangelo A1 - Malgesini, Sara A1 - Crichiutti, Giovanni A1 - Balestri, Paolo A1 - Grosso, Salvatore A1 - Zamponi, Nelia A1 - Incorpora, Gemma A1 - Savasta, Salvatore A1 - Costa, Paola A1 - Pruna, Dario A1 - Cusmai, Raffaella KW - Adolescent KW - Anticonvulsants KW - Attention Deficit Disorder with Hyperactivity KW - Child KW - Child, Preschool KW - Electroencephalography KW - Epilepsy KW - Female KW - Gastroenteritis KW - Humans KW - Longitudinal Studies KW - Male KW - Neurologic Examination KW - Retrospective Studies AB -

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.

VL - 18 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/24780603?dopt=Abstract ER -