Early 2020, a COVID-19 epidemic became a public health emergency of international concern. To address this pandemic broad testing with an easy, comfortable and reliable testing method is of utmost ...concern. Nasopharyngeal (NP) swab sampling is the reference method though hampered by international supply shortages. A new oropharyngeal/nasal (OP/N) sampling method was investigated using the more readily available throat swab.
35 patients were diagnosed with SARS-CoV-2 by means of either NP or OP/N sampling. The paired swabs were both positive in 31 patients. The one patient who tested negative on both NP and OP/N swab on admission, was ultimately diagnosed on bronchoalveolar lavage fluid. A strong correlation was found between the viral RNA loads of the paired swabs (r = 0.76; P < 0.05). The sensitivity of NP and OP/N analysis in hospitalized patients (n = 28) was 89.3% and 92.7% respectively.
This study demonstrates equivalence of NP and OP/N sampling for detection of SARS-CoV-2 by means of rRT-PCR. Sensitivity of both NP and OP/N sampling is very high in hospitalized patients.
The aims of this study were to assess the characteristics of all acute poisoning admissions among adult emergency department (ED) patients, to identify factors associated with admission and to ...calculate direct medical cost.
Data of 2017 (1st January to 31st December) were collected and analyzed retrospectively using patients' medical records and hospital invoices. Factors associated with type of hospitalization were identified using appropriate statistics.
A total of 1,214 hospital admissions were included, accounting for 3.6% of all ED admissions. Men (62.2%) and the age group 21-40 years (43.0%) accounted for the largest proportion. Substances most commonly involved were ethanol (52.9%), benzodiazepines (9.7%), cocaine (4.9%), cannabis (4.6%), antidepressants (4.6%) and psychostimulants (4.6%). A total of 4,561 treatment acts were recorded, most commonly monitoring of vital signs (63.6%) and medication and/or intravenous drip administration (62.9%). Patients were discharged home after having received care in the emergency department (ED-amb) in 54.5% of admissions, were admitted to the emergency-department-24-hours-observation unit (ED-24h) or were hospitalized (Hosp) in 24.6% and 20.9% of admissions, respectively. Factors found to be associated with hospitalization type were age, hour of admission, victim location, degree of severity, use of antidotes, involvement of antidepressants, antipsychotics, psychostimulants, benzodiazepines and ethanol. Total cost was €1,512,346 with an average of €1,287 per admission.
Poisonings entail a considerable percentage of patients admitted to an ED and financial burden. In particular, ethanol poisonings account for the largest proportion of all ED admissions. Comparison of our figures with other data is hampered by the heterogeneity in inclusion criteria. Availability of a uniform template would facilitate comparison and allow better monitoring policies for prevention and cost reduction.
There is little data available to guide amoxicillin-clavulanic acid dosing in critically ill children. The primary objective of this study was to investigate the pharmacokinetics of both compounds in ...this pediatric subpopulation. Patients admitted to the pediatric intensive care unit (ICU) in whom intravenous amoxicillin-clavulanic acid was indicated (25 to 35 mg/kg of body weight every 6 h) were enrolled. Population pharmacokinetic analysis was conducted, and the clinical outcome was documented. A total of 325 and 151 blood samples were collected from 50 patients (median age, 2.58 years; age range, 1 month to 15 years) treated with amoxicillin and clavulanic acid, respectively. A three-compartment model for amoxicillin and a two-compartment model for clavulanic acid best described the data, in which allometric weight scaling and maturation functions were added a priori to scale for size and age. In addition, plasma cystatin C and concomitant treatment with vasopressors were identified to have a significant influence on amoxicillin clearance. The typical population values of clearance for amoxicillin and clavulanic acid were 17.97 liters/h/70 kg and 12.20 liters/h/70 kg, respectively. In 32% of the treated patients, amoxicillin-clavulanic acid therapy was stopped prematurely due to clinical failure, and the patient was switched to broader-spectrum antibiotic treatment. Monte Carlo simulations demonstrated that four-hourly dosing of 25 mg/kg was required to achieve the therapeutic target for both amoxicillin and clavulanic acid. For patients with augmented renal function, a 1-h infusion was preferable to bolus dosing. Current published dosing regimens result in subtherapeutic concentrations in the early period of sepsis due to augmented renal clearance, which risks clinical failure in critically ill children, and therefore need to be updated. (This study has been registered at Clinicaltrials.gov as an observational study NCT02456974.).
Background
Correct dosing and therapeutic drug monitoring (TDM) practices are essential when aiming for optimal vancomycin treatment.
Objective
To assess target attainment after initial dosing and ...dose adjustments, and to determine compliance to dosing and TDM guidelines.
Setting
Tertiary care university hospital in Belgium.
Method
A chart review was performed in 150 patients, ranging from preterm infants to adults, treated intravenously with vancomycin. Patient characteristics, dosing and TDM data were compared to evidence-based hospital guidelines.
Main outcome measures
Target attainment of vancomycin after initial dosing and dose adjustments.
Results
Subtherapeutic concentrations were measured in 68% of adults, in 76% of children and in 52% of neonates after treatment initiation. Multiple dose adaptations (median 2, Q1 1–Q3 2) were required for target attainment, whilst more than 20% of children and neonates never reached targeted concentrations. Regarding compliance to the hospital guideline, some points of improvement were identified: omitted dose adjustment in adults with decreased renal function (53%), delayed sampling (16% in adults, 31% in children) and redundant sampling (34% of all samples in adults, 12% in children, 13% in neonates).
Conclusion
Target attainment for vancomycin with current dosing regimens and TDM is poor in all age groups. Besides, human factors should not be ignored when aiming for optimal treatment. This study reflects an ongoing challenge in clinical practice and highlights the need for optimization of vancomycin dosing strategies and improvement of awareness of all health care professionals involved.
To characterize the population pharmacokinetics of piperacillin and tazobactam in critically ill infants and children, in order to develop an evidence-based dosing regimen.
This pharmacokinetic study ...enrolled patients admitted to the paediatric ICU for whom intravenous piperacillin/tazobactam (8:1 ratio) was indicated (75 mg/kg every 6 h based on piperacillin). Piperacillin/tazobactam concentrations were measured by an LC-MS/MS method. Pharmacokinetic data were analysed using non-linear mixed effects modelling.
Piperacillin and tazobactam blood samples were collected from 47 patients (median age 2.83 years; range 2 months to 15 years). Piperacillin and tazobactam disposition was best described by a two-compartment model that included allometric scaling and a maturation function to account for the effect of growth and age. Mean clearance estimates for piperacillin and tazobactam were 4.00 and 3.01 L/h for a child of 14 kg. Monte Carlo simulations showed that an intermittent infusion of 75 mg/kg (based on piperacillin) every 4 h over 2 h, 100 mg/kg every 4 h given over 1 h or a loading dose of 75 mg/kg followed by a continuous infusion of 300 mg/kg/24 h were the minimal requirements to achieve the therapeutic targets for piperacillin (60% f T >MIC >16 mg/L).
Standard intermittent dosing regimens do not ensure optimal piperacillin/tazobactam exposure in critically ill patients, thereby risking treatment failure. The use of a loading dose followed by a continuous infusion is recommended for treatment of severe infections in children >2 months of age.
A high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed and validated for the simultaneous quantification of ofloxacin, ciprofloxacin and moxifloxacin in ...human plasma. Sarafloxacin was used as internal standard. Chromatography was carried out using a Waters XBridge™ C
18 HPLC column and a gradient mobile phase consisting of CH
3CN/MeOH/0.025
M TBA·Cl/TFA (eluent A at 75/25/899/1 (v/v); eluent B at 150/50/799/1 (v/v); both at pH 3.5). Excitation/emission wavelengths were 279/442
nm for ciprofloxacin and 290/500
nm for ofloxacin, moxifloxacin and internal standard. Prior to chromatography, plasma samples were treated with acetonitrile for protein precipitation, followed by evaporation of the liquid layer and reconstitution in eluent A. The method was validated for the three fluoroquinolones over the clinically relevant concentration range from 0.02 to 7.50
μg/ml. The method showed acceptable linearity with correlation coefficients,
r
2
>
0.995, as well as high precision (RSD% <7% in each case), accuracy (90.4–105.4%) and selectivity. The limit of quantification for the three fluoroquinolones was established at 0.02
μg/ml. Ofloxacin, ciprofloxacin and moxifloxacin were extracted from plasma with a mean recovery of 95%, 86.4% and 94.2%, respectively. During validation, the concentration of the three fluoroquinolones was found to be stable after 3 freeze–thaw cycles and for at least 15
h after extraction. This bio-analytical method was finally applied to the analysis of samples which have been obtained from patients, participating in a pharmacokinetic study on moxifloxacin.
BACKGROUND:Propofol is a short-acting intravenous anesthetic agent. In rare conditions, a life-threatening complication known as propofol infusion syndrome can occur. The pathophysiologic mechanism ...is still unknown. Some studies suggested that propofol acts as uncoupling agent, others suggested that it inhibits complex I or complex IV, or causes increased oxidation of cytochrome c and cytochrome aa3, or inhibits mitochondrial fatty acid metabolism. Although the exact site of interaction is not known, most hypotheses point to the direction of the mitochondria.
METHODS:Eight rats were ventilated and sedated with propofol up to 20 h. Sequential biopsy specimens were taken from liver and skeletal muscle and used for determination of respiratory chain activities and propofol concentration. Activities were also measured in skeletal muscle from a patient who died of propofol infusion syndrome.
RESULTS:In rats, authors detected a decrease in complex II+III activity starting at low tissue concentration of propofol (20 to 25 µM), further declining at higher concentrations. Before starting anesthesia, the complex II+III/citrate synthase activity ratio in liver was 0.46 (0.25) and in skeletal muscle 0.23 (0.05) (mean SD). After 20 h of anesthesia, the ratios declined to 0.17 (0.03) and 0.12 (0.02), respectively. When measured individually, the activities of complexes II and III remained normal. Skeletal muscle from one patient taken in the acute phase of propofol infusion syndrome also shows a selective decrease in complex II+III activity (z-score−2.96).
CONCLUSION:Propofol impedes the electron flow through the respiratory chain and coenzyme Q is the main site of interaction with propofol.
IntroductionCritical illness may affect many pharmacokinetic (PK) processes. Research in adults suggests an impaired tissue penetration of beta-lactam antibiotics in critically ill patients compared ...to healthy individuals. Currently, data in critically ill children are lacking. This study aimed (1) to investigate the tissue penetration of piperacillin-tazobactam, a frequently used broad-spectrum beta-lactam/beta-lactamase inhibitor combination and (2) to assess the safety of microdialysis experiments in critically ill children. MethodologyThis pilot study included seven mechanically ventilated children (age range: 1 month - 13 years) receiving piperacillin-tazobactam (75 mg per kg bodyweight, based on the piperacillin component, every 6 h as a 30 min infusion). A microdialysis catheter (10 mm membrane) was inserted in the thigh muscle. Benzylpenicillin was used as internal standard for microdialysis calibration. During one or two dosing intervals, plasma and microdialysis samples were collected (max. stay of microdialysis catheter: 35 h). PK data were analyzed with non-compartmental PK analysis (Phoenix®, Certara). The tissue penetration was calculated by taking the ratio of the AUC(0-inf) in tissue and in plasma. ResultsIn total, 12 dosing intervals were sampled. Median tissue penetration was 0.68 (IQR 0.55 – 0.84) for piperacillin and 1.10 (0.92 – 1.38) for tazobactam. The extrapolated part of the AUC(0-inf) accounted for less than 20% of the total AUC(0-inf). No adverse events occurred during microdialysis catheter insertion, microdialysis sampling, and catheter removal.ConclusionTo the best of our knowledge, this study is the first to report on tissue penetration of piperacillin-tazobactam in critically ill children. Similarly to what was found in critically ill adult patients (septic shock cohort (Joukhadar 2001): mean 0.19 ± SE 0.03/post cardiac surgery cohort (Brunner 2000): mean 0.27 ± SE 0.04), the tissue penetration of piperacillin is impaired in critically ill children, albeit to a lesser extent than what has been reported in critically ill adults. These findings underscore the limitations of plasma as a surrogate for tissue exposure in critical illness. Contrary to general belief, this study shows that piperacillin and tazobactam have a different PK behavior, with a good tissue penetration of the beta-lactamase inhibitor. Microdialysis is a safe and feasible method for tissue pharmacokinetic research in critically ill children.
Disulfiram is an adjunct in the treatment of alcohol use disorders, but case reports indicate that disulfiram ethanol reactions are not always recognized in the emergency department. Our first aim is ...to remind of this risk with two case reports of life-threatening reactions not immediately considered by the emergency physician. The second aim is to estimate the probability that a disulfiram reaction goes unrecognized with the use of a retrospective study of patients admitted to the emergency department.
Clinical files of patients admitted between October 1, 2010 and September 30, 2014 to the emergency department were retrospectively screened for the key words "ethanol use" and "disulfiram". Their diagnoses were then scored by a panel regarding the probability of an interaction.
Seventy-nine patients were included, and a disulfiram-ethanol reaction was scored as either 'highly likely', 'likely' or 'possible' in 54.4% and as 'doubtful' or 'certainly not present' in 45.6% of the patients. The interrater agreement was 0.71 (95% CI: 0.64-0.79). The diagnosis was not considered or only after a delay in 44.2% of the patients with a 'possible' to 'highly likely' disulfiram interaction. One patient with a disulfiram overdose died and was considered as a 'possible' interaction.
A disulfiram ethanol interaction can be life threatening and failure to consider the diagnosis in the emergency department seems frequent. Prospective studies with documentation of the intake of disulfiram and evaluation of the value of acetaldehyde as a biomarker are needed to determine the precise incidence. Improving knowledge of disulfiram interactions and adequate history taking of disulfiram intake may improve the care for patients.
Augmented renal clearance (ARC) observed in the critically ill pediatric population has received an increased attention over the last years due to its major impact on the disposition and ...pharmacokinetics of mainly renally excreted drugs. Apart from an important inflammatory trigger, fluid administration has been suggested to contribute to the development of ARC. Therefore, the primary objective of this study was to evaluate the effect of continuous intravenous fluid administration on renal function using a conventional piglet animal model and to quantify the impact of fluid administration on the pharmacokinetics of renally excreted drugs. At baseline, twenty-four piglets (12 treatment/12 control; 7 weeks old, all ♂) received the marker drugs iohexol (64.7 mg/kg body weight (BW)) and para-aminohippuric acid (10 mg/kg BW) to quantify glomerular filtration rate and effective renal plasma flow, respectively. In addition, the hydrophilic antibiotic amikacin (7.5 mg/kg BW) was administered. Following this baseline measurement, the treatment group received fluid therapy as a constant rate infusion of 0.9% saline at 6 mL/kg/h over 36 h. After 24 h of fluid administration, the marker drugs and amikacin were administered again. When comparing both groups, a significant effect of fluid administration on the total body clearances of iohexol (
= 0.032) and amikacin (
= 0.0014) was observed. Clearances of iohexol and amikacin increased with on average 15 and 14%, although large interindividual variability was observed. This led to decreased systemic exposure to amikacin, which was manifested as decrease in area under the plasma concentration-time curve from time 0 h to infinity from 34,807 to 30,804 ng.h/mL. These results suggest that fluid therapy is a key factor involved in the development of ARC and should be taken into account when administering mainly renally excreted drugs. However, further research is necessary to confirm these results in children.
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