Paediatric pharmacokinetics: key considerations.

A number of anatomical and physiological factors determine the pharmacokinetic profile of a drug. Differences in physiology in paediatric populations compared with adults can influence the concentration of drug within the plasma or tissue. Healthcare professionals need to be aware of anatomical and physiological changes that affect pharmacokinetic profiles of drugs to understand consequences of dose adjustments in infants and children. Pharmacokinetic clinical trials in children are complicated owing to the limitations on blood sample volumes and perception of pain in children resulting from blood sampling. There are alternative sampling techniques that can minimize the invasive nature of such trials. Population based models can also limit the sampling required from each individual by increasing the overall sample size to generate robust pharmacokinetic data. This review details key considerations in the design and development of paediatric pharmacokinetic clinical trials.

Infant Escherichia coli urinary tract infection: is it associated with meningitis?

OBJECTIVES: Determine the prevalence of coexisting bacterial meningitis (BM) and sterile cerebrospinal fluid (CSF) with raised white cell count relative to age ('pleocytosis') in the presence of Escherichia coli urinary tract infection (UTI), with the addition of CSF E. coli PCR analysis. DESIGN: Single-centre, retrospective cohort study. SETTING: Tertiary paediatric hospital. PARTICIPANTS: Children aged 8 days to 2 years, with a pure growth of E. coli from urine and a CSF sample taken within 48 hours of a positive urine culture between 1 January 2014 and 30 April 2019. MAIN OUTCOME MEASURE: Prevalence of coexisting E. coli BM with UTI, defined as a pure growth E. coli from urine and a CSF culture with pure growth E. coli and/or positive E. coli PCR. RESULTS: 1903 patients had an E. coli UTI, of which 314 (16%) had a CSF sample taken within 48 hours. No cases of coexisting E. coli BM were identified. There were 71 (23%) cases of pleocytosis, 57 (80%) of these had PCR analysis, all of which were E. coli PCR not detected. Patients aged 1-6 months accounted for 72% of all lumbar punctures (LPs). CONCLUSION: The risk of E. coli UTI and coexisting E. coli BM is low. There is potential to reduce the number of routine LPs in infants with a diagnosis of E. coli UTI with the greatest impact in children up to 6 months of age. CSF E. coli PCR can help further reduce post-test probability of BM in the setting of pleocytosis.