In this paper, we describe the case of a patient admitted to our hospital because of a brain abscess due to Streptococcus intermedius. The management of brain abscess is challenging given the limited potential drug options with effective penetration into both the central nervous system and the abscess capsule to achieve adequate therapeutic concentrations. Due to the high anti-streptococcal activity of ceftobiprole and the availability of ceftobiprole therapeutic drug monitoring in our hospital, we decided to treat the patient with ceftobiprole. To maximize the antimicrobial effect of ceftobiprole, we chose a prolonged intravenous infusion, and we monitored its concentrations in both plasma and cerebrospinal fluid.

Vancomycin is a glycopeptide antibiotic used for prophylaxis and treatment of infections caused by methicillin-resistant Staphylococcus aureus. Although major organ sizes and functions mature during infancy, pharmacokinetic studies, especially those focused on infants, are limited. Changes in extracorporeal membrane oxygenation-related drug disposition largely contribute to changes in pharmacokinetics. Here, pharmacokinetic profiles of vancomycin in an infant receiving extracorporeal membrane oxygenation therapy are presented. A two-month-old Japanese infant with moderately decreased renal function was started on 12.0 mg/kg vancomycin every 8 h from day X for prophylaxis of pneumonia during extracorporeal membrane oxygenation therapy. As the trough concentration of vancomycin observed on day X+3 was 27.1 μg/mL, vancomycin was then discontinued. The trough concentration decreased to 18.6 μg/mL 24 h after discontinuation, and 9.0 mg/kg vancomycin every 12 h was restarted from day X+5. On day X+6, the trough concentration increased to 36.1 μg/mL, and vancomycin therapy was again discontinued. On day X+7, the trough concentration decreased to 22.4 μg/mL. The pharmacokinetic profiles of vancomycin based on first-order conditional estimation in this infant were as follows: plasma clearance = 0.053 L/kg/hour, distribution volume = 2.19 L/kg, and half-life = 29.5 h. This research reported the prolonged half-life of vancomycin during extracorporeal membrane oxygenation in infants with moderately decreased renal function.

To describe the peramivir (PRV) pharmacokinetics in critically ill children treated for influenza A or B viral infections.
Retrospective electronic medical record review of prospectively collected data from critically ill children receiving peramivir for influenza A or B viral infections in the pediatric intensive care unit (PICU).
A 189-bed, freestanding children\'s tertiary care teaching hospital in Philadelphia, PA.
Critically ill children admitted to the PICU who were infected with influenza between January 1, 2016 and March 31, 2018.
None.
Eleven patients, two females (18%) and nine males (82%), accounted for 24 peramivir samples for therapeutic drug management. The median age was 5 years (interquartile range 1.5-6.5 yrs) with a median weight of 16.4 kg (interquartile range 14-24 kg). Ten (91%) patients demonstrated a larger volume of distribution, 11 (100%) patients demonstrated an increase in clearance, and 11 (100%) patients demonstrated a shorter half-life estimate as compared with the package insert and previous pediatric trial data for peramivir. Eight (73%) patients tested positive for a strain of influenza A and 3 (27%) patients tested positive for influenza B; 4 of 11 (36%) patients tested positive for multiple viruses. All patients had adjustments made to their dosing interval to a more frequent interval. Ten (91%) patients were adjusted to an every-12-hour regimen and 1 (9%) patient was adjusted to an every-8-hour regimen. No adverse events were associated with peramivir treatment.
The pharmacokinetics of PRV demonstrated in this PICU cohort differs in comparison to healthy pediatric and adult patients, and alterations to dosing regimens may be needed in PICU patients to achieve pharmacodynamic exposures. Additional investigations in the PICU population are needed to confirm these findings.

The first Paediatric Use Marketing Authorisation was approved in Europe in 2011. This article describes the assessment procedure and the key regulatory issues that were addressed.

Drug manufacturer seeking authorization to bring a newly medicinal compound to the market (Market Authorization Application) have to undertake various studies, each of them providing a specific report. It is however essential to know how to pool results in order to understand the behavior of the drug in all the situations likely to be encountered in clinical practice. The exploitation of these data is now carried out through pharmacometric analyzes which aim at quantifying the exposure and the response of a drug over time. These methods (named \"population approach\") are based on non-linear mixed effects model and therefore, on the identification of a mathematical model. A first step is to model the variations in concentrations over time by integrating the physio-pathological characteristics of the patients. At this stage, the Bayesian analysis is essential to identify and select the factors of interindividual variability. This pharmacokinetic (PK) modeling allows us to obtain the prescribed dose for each patient, but also their exposure. The second step consists in defining the relationship between exposure and effect: pharmacodynamic (PD) modeling. In psychiatry, the response can be the receptors\' occupancy rate or the evolution of a clinical score (BPRS, PANSS…) over time. The final PK-PD model defines the target exposure, that is to say, the concentration values required to achieve maximum effect on the score studied without risking over-exposure. Ultimately, a Monte Carlo simulation will be conducted which will test the expected response for different doses and will facilitate a rational choice in dosage. Assessing the process behind the transition from an oral to a long-acting injectable form of an active ingredient such as aripiprazole can be done by following the same protocol. A 10- to 30-mg per day therapeutic range has thus been identified. The model incorporates all the identified factors of variability of aripiprazole (drug interactions and genetic polymorphism of the P450 2D6 cytochrome) and showed that with an injectable sustained release form, a monthly dose of 400mg would allow 90% of patients to gain exposure in the therapeutic range. In case of a drug inhibition and/or of a slow metabolizing profile, dosage adjustment is necessary.