@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 {7707, title = {Pharmacokinetics and pharmacodynamics of continuous-infusion meropenem in pediatric hematopoietic stem cell transplant patients.}, journal = {Antimicrob Agents Chemother}, volume = {59}, year = {2015}, month = {2015 Sep}, pages = {5535-41}, abstract = {

This study explored the pharmacokinetics and the pharmacodynamics of continuous-infusion meropenem in a population of pediatric hematopoietic stem cell transplant (HSCT) patients who underwent therapeutic drug monitoring. The relationship between meropenem clearance (CLM) and estimated creatinine clearance (CLCR) was assessed by nonlinear regression. A Monte Carlo simulation was performed to investigate the predictive performance of five dosing regimens (15 to 90 mg/kg of body weight/day) for the empirical treatment of severe Gram-negative-related infections in relation to four different categories of renal function. The optimal target was defined as a probability of target attainment (PTA) of >=90\% at steady-state concentration-to-MIC ratios (C SS/MIC) of >=1 and >=4 for MICs of up to 8 mg/liter. A total of 21 patients with 44 meropenem C SS were included. A good relationship between CLM and estimated CLCR was observed (r (2) = 0.733). Simulations showed that at an MIC of 2 mg/liter, the administration of continuous-infusion meropenem at doses of 15, 30, 45, and 60 mg/kg/day may achieve a PTA of >=90\% at a C SS/MIC ratio of >=4 in the CLCR categories of 40 to <80, 80 to <120, 120 to <200, and 200 to <300 ml/min/1.73 m(2), respectively. At an MIC of 8 mg/liter, doses of up to 90 mg/kg/day by continuous infusion may achieve optimal PTA only in the CLCR categories of 40 to <80 and 80 to <120 ml/min/1.73 m(2). Continuous-infusion meropenem at dosages up to 90 mg/kg/day might be effective for optimal treatment of severe Gram-negative-related infections in pediatric HSCT patients, even when caused by carbapenem-resistant pathogens with an MIC of up to 8 mg/liter.

}, issn = {1098-6596}, doi = {10.1128/AAC.00787-15}, author = {Cojutti, Piergiorgio and Maximova, Natalia and Pea, Federico} } @article {7704, title = {Polyclonal gammopathy after BKV infection in HSCT recipient: a novel trigger for plasma cells replication?}, journal = {Virol J}, volume = {12}, year = {2015}, month = {2015}, pages = {23}, abstract = {

BACKGROUND: BK polyomavirus infects most of the general population. However, its clinical manifestations are almost exclusively seen in immunocompromised patients, particularly in kidney and hematopoietic stem cell transplantation recipients.

CASE PRESENTATION: A 15-y-old female suffering from common B-cell acute lymphoblastic leukaemia underwent hematopoietic stem cell transplantation. The patient had reactivation of BKPyV infection and developed an haemorrhagic cystitis. Three months after transplant, BKPyV viremia and viruria increased and she developed a severe nephropathy associated to a polyclonal gammopathy with high levels of isolated IgM.

CONCLUSION: This case report describes a rare and unexpected polyclonal gammopathy developed during a polyomavirus-associated nephropathy confirmed by immunohistochemical and laboratory analyses.

}, issn = {1743-422X}, doi = {10.1186/s12985-015-0254-z}, author = {Maximova, Natalia and Pizzol, Antonio and Sonzogni, Aurelio and Gregori, Massimo and Granzotto, Marilena and Tamaro, Paolo} }