Modifiable risk factors associated with later gut decolonization of carbapenem-resistant Gram-negative bacteria in children: a prospective cohort study.

BACKGROUND: Nosocomial infections caused by carbapenem-resistant Gram-negative bacteria (CRGNB) are associated with increased mortality and prolonged hospitalization; thus, later CRGNB decolonization has significant clinical and public health implications. AIM: To investigate modifiable/non-modifiable risk factors for CRGNB later gut decolonization in children. METHODS: CRGNB carriers (aged from one day to 16 years) hospitalized in a tertiary level hospital (2018-2019) were included. Upon CRGNB carriage detection, rectal swab cultures were taken weekly, if patients were hospitalized, and monthly after discharge for 12 months. CRGNB decolonization was defined as three consecutive negative rectal-swab cultures obtained ≥1 week apart. Modifiable (treatment administered/medical devices) and non-modifiable (age/gender/comorbidities) risk factors were recorded. Cox regression for later CRGNB decolonization was performed. FINDINGS: One hundred and thirty CRGNB carriers were recorded. After 12 months, 5.4% remained carriers. Risk factors for later decolonization were immunosuppression (hazard ratio: 0.52; 95% confidence interval: 0.31-0.87), carbapenems (0.52; 0.30-0.91), proton pump inhibitors (PPIs) (0.39; 0.24-0.64) and their duration of use, duration of hospitalization (0.90; 0.81-0.92, per 10 days), number of readmissions (0.90; 0.86-0.96), abdominal surgery (0.33; 0.17-0.65), urinary catheter (0.42; 0.24-0.76), and duration of steroid administration per 10 days (0.86; 0.84-0.88). CONCLUSIONS: Carbapenems, PPIs and their duration of use, duration of steroids use, immunosuppression, urinary catheter, readmissions, duration of hospitalization, and abdominal surgery are associated with later CRGNB decolonization among children. Paediatric patients at risk of later decolonization should be under targeted screening and pre-emptive contact precautions. Known carriers at risk of later CRGNB decolonization should be under meticulously applied contact precautions for longer durations.

Population Pharmacokinetics of Teicoplanin in Preterm and Term Neonates: Is It Time for a New Dosing Regimen?

Our objective was to develop a population pharmacokinetic (PK) model in order to evaluate the currently recommended dosing regimen in term and preterm neonates. By using an optimal design approach, a prospective PK study was designed and implemented in 60 neonates with postmenstrual ages (PMA) of 26 to 43 weeks. A loading dose of 16 mg/kg was administered at day 1, followed by a maintenance dose of 8 mg/kg daily. Plasma concentrations were quantified by high-pressure liquid chromatography-mass spectrometry. Population PK (popPK) analysis was performed using NONMEM software. Monte-Carlo (MC) simulations were performed to evaluate currently recommended dosing based on a pharmacodynamic index of area under the concentration-time curve (AUC)/MIC ratio of ≥400. A two-compartment model with linear elimination best described the data by the following equations: clearance (CL) = 0.0227 × (weight [wt]/1,765)0.75 × (estimated creatinine clearance [eCRCL]/22)0.672, central compartment volume of distribution (V1) = 0.283 (wt/1,765), intercompartmental clearance (Q) = 0.151 (wt/1,765)0.75, and peripheral compartment volume (V2) = 0.541 (wt/1,765). The interindividual variability estimates for CL, V1, and V2 were 36.5%, 45.7%, and 51.4%, respectively. Current weight (wt) and estimated creatinine clearance (eCRCL) significantly explained the observed variability. MC simulation demonstrated that, with the current dosing regimen, an AUC/MIC ratio of ≥400 was reached by only 68.5% of neonates with wt of <1 kg when the MIC was equal to 1 mg/kg, versus 82.2%, 89.7%, and 92.7% of neonates with wt of 1 to <2, 2 to <3, or ≥3 kg, respectively. Augmentation of a maintenance dose up to 10 or 11 mg/kg for preterm neonates with wt of 1 to <2 or <1 kg, respectively, increases the probability of reaching the therapeutic target; the recommended doses seem to be adequate for neonates with wt of ≥2 kg. Teicoplanin PK are variable in neonates, with wt and eCRCL having the most significant impact. Neonates with wt of <2 kg need higher doses, especially for Staphylococcus spp. with an MIC value of ≥1 mg/liter.

An ultra-high pressure liquid chromatography-tandem mass spectrometry method for the quantification of teicoplanin in plasma of neonates.

The development and validation of an ultra-high pressure liquid chromatography (UHPLC) tandem mass spectrometry (MS/MS) method was performed with the aim to be applied for the quantification of plasma teicoplanin concentrations in neonates. Pharmacokinetic data of teicoplanin in the neonatal population is very limited, therefore, a sensitive and reliable method for the determination of all isoforms of teicoplanin applied in a low volume of sample is of real importance. Teicoplanin main components were extracted by a simple acetonitrile precipitation step and analysed on a C18 chromatographic column by a triple quadrupole MS with electrospray ionization. The method provides quantitative data over a linear range of 25-6400ng/mL with LOD 8.5ng/mL and LOQ 25ng/mL for total teicoplanin. The method was applied in plasma samples from neonates to support pharmacokinetic data and proved to be a reliable and fast method for the quantification of teicoplanin concentration levels in plasma of infants during therapy in Intensive Care Unit.