Use of linezolid in infants and children: a retrospective multicentre study of the Italian Society for Paediatric Infectious Diseases.

OBJECTIVES: Because of the spread of drug-resistant Gram-positive bacteria, the use of linezolid for treating severe infections is increasing. However, clinical experience in the paediatric population is still limited. We undertook a multicentre study to analyse the use of linezolid in children. METHODS: Hospitalized children treated with linezolid for a suspected or proven Gram-positive or mycobacterial infection were analysed retrospectively. Side effects were investigated, focusing on younger children and long-term treatments. RESULTS: Seventy-five patients (mean age 6.8 years, range 7 days to 17 years) were studied. Mean ±â€ŠSD linezolid treatment duration was 26.13 ±â€Š17 days. Clinical cure was achieved in 74.7% of patients. The most frequent adverse events were diarrhoea and vomiting. Two patients had severe anaemia, two neutropenia and one thrombocytopenia. Two cases of grade 3 liver function test elevation and one case of pancreatitis were reported. The overall frequency of adverse events was similar between patients treated for >28 days and those receiving shorter treatments (30.8% versus 28.6%, P = 0.84). Children aged <2 years received linezolid for a shorter duration than older children (21.2 days versus 28.4 days, P = 0.05), whereas the frequency of adverse events was similar in the two age groups. CONCLUSIONS: In our paediatric population, linezolid appeared safe and effective for the treatment of selected Gram-positive and mycobacterial infections. The adverse reactions encountered were reversible and appeared comparable to those reported in paediatric clinical trials. Nevertheless, the potential for haematological toxicity of linezolid in children means that careful monitoring is required during treatment.

Kikuchi-Fujimoto disease causing fever of unknown origin in a nine-year-old boy.

We describe a case of fever of unknown origin (FUO) in a 9-y-old boy finally diagnosed with Kikuchi-Fujimoto disease (KFD) and discuss the implications for the management of FUO in children. KFD should be considered in the differential diagnosis of patients presenting with FUO to prevent misdiagnosis and inappropriate treatment.

Your diagnosis? A 12-year-old girl with latent tuberculosis presenting with nausea, vomiting and increasing frontal headache.

A 12-year-old girl with latent Mycobacterium tuberculosis infection and currently receiving prophylaxis with isoniazid presented with nausea, vomiting and increasing frontal headache. Toxicity to the anti-tuberculosis drug was suspected, but her symptoms persisted after isoniazid withdrawal. A computed tomography (CT) scan showed a brain mass to be present.

Rapid and sensitive LC-MS/MS method for the analysis of antibiotic linezolid on dried blood spot.

Linezolid is a new drug from the oxazolidinone class of antibiotics used against mycobacteria and multi-drug resistant (MDR) Gram-positive bacterial infections, which may are also glycopeptide-resistant. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to determinate linezolid levels during treatment. Advantages of DBS include short collection time, low invasiveness, ease and low cost of sample collection, transport and storage. The analysis was performed in LC-MS/MS operating in positive ion mode and multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 1-100 mg/L with correlation coefficient value of 0.9987. Intraday and interday coefficients of variation were within 3.6% and 13.0%, respectively. We also tested the thermal and temporal drug stability in dried blood spots at four different temperatures to evaluate the risks of sample delivery in different conditions. The short term stability studies showed that linezolid concentration remained stable for at least one month under all the conditions tested. This new assay has favorable characteristics being highly precise and accurate and allows a fast linezolid analysis with a total run time 22 min long, in gradient analysis. Concentration data for plasma and DBS samples from patients after treatment were compared showing a good correlation. Correlation between DBS data and serum samples measured by HPLC-UV was satisfactory. The benefit for patients is the ability to monitor the treatment with a simple and convenient sample collection at home.

Development of an UPLC-MS/MS method for the determination of antibiotic ertapenem on dried blood spots.

Ertapenem (Invanz) is a newly developed carbapenem ß-lactam antimicrobial agent. The drug usage in pediatric age needs an accurate drug monitoring for effective patient management. The aim of this study was to evaluate the use of dried blood spot (DBS) specimens to measure ertapenem concentration during treatment. The analysis was performed by UPLC-MS/MS operating in multiple reaction monitoring (MRM) mode. The calibration curve in matrix was linear in the concentration range of 0.5-100 mg/L with correlation coefficient value higher than 0.997. Performance parameters of this method like lower limit of detection (LLOD, 0.2 mg/L), lower limit of quantification (LLOQ, 0.5 mg/L), matrix effect (20%), intra- and inter-day imprecision (CV within than 15%) and accuracy (between 94 and 155%) of drug concentrations have been evaluated. The drug stability at different temperatures was tested for one month, to evaluate the risks of sample delivery at different climatic conditions. The reported method allows now ertapenem analysis and offers many advantages for patients including the possibility of collecting samples at home. This new assay is both precise and accurate and is especially suitable for therapeutic drug monitoring and pharmacokinetic studies in neonates in whom obtaining larger blood samples is not convenient or possible.