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      Adverse reaction to ceftriaxone in a 28-day-old infant undergoing urgent craniotomy due to epidural hematoma: review of neonatal biliary pseudolithiasis

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          Abstract

          The debate as to whether to administer ceftriaxone to neonates is likely to continue. Ceftriaxone has numerous advantages for critically ill pediatric patients. However, it is also known to contribute substantially to the development of biliary pseudolithiasis. Although pediatric patients rarely develop gallbladder disorders, this complication may lead to adverse events in high-risk patients with predisposing factors, particularly in neonates and infants treated with ceftriaxone. In this paper we present an interesting case report of a 28-day-old neonate with spontaneous severe epidural hematoma who developed biliary pseudolithiasis related to the use of ceftriaxone. We also discuss the efficacy of ceftriaxone in neonates and infants. Neonatologists and pediatric intensivists should be aware of the higher risk of co-existence of hyperbilirubinemia and gallbladder disorders while using ceftriaxone in pediatric settings.

          Most cited references35

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          Antibiotic allergies in children and adults: from clinical symptoms to skin testing diagnosis.

          Hypersensitivity reactions to β-lactam and non-β-lactam antibiotics are commonly reported. They can be classified as immediate or nonimmediate according to the time interval between the last drug administration and their onset. Immediate reactions occur within 1 hour after the last drug administration and are manifested clinically by urticaria and/or angioedema, rhinitis, bronchospasm, and anaphylactic shock; they may be mediated by specific IgE-antibodies. Nonimmediate reactions occur more than 1 hour after the last drug administration. The most common manifestations are maculopapular exanthems; specific T lymphocytes may be involved in this type of manifestation. The diagnostic evaluation of hypersensitivity reactions to antibiotics is usually complex. The patient's history is fundamental; the allergic examination is based mainly on in vivo tests selected on the basis of the clinical features and the type of reaction, immediate or nonimmediate. Immediate reactions can be assessed by immediate-reading skin tests and, in selected cases, drug provocation tests. Nonimmediate reactions can be assessed by delayed-reading skin tests, patch tests, and drug provocation tests. However, skin tests have been well validated mainly for β-lactams but less for other classes of antibiotics.
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            Clinical pharmacology of midazolam in infants and children.

            Midazolam is a parenteral benzodiazepine with sedative, amnesic, anxiolytic, muscle relaxant and anticonvulsant properties. The drug exerts its clinical effect by binding to a receptor complex which facilitates the action of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Midazolam has a faster onset and shorter duration of action than other benzodiazepines such as diazepam and lorazepam. The most serious adverse events associated with midazolam in children include hypoventilation, decreased oxygen saturation, apnoea and hypotension. It is water soluble in the commercially prepared formulation but becomes lipid soluble at physiological pH and can then cross the blood brain barrier. It is metabolised in the liver by the cytochrome P450 system, and its chief metabolite is 1-hydroxymethyl midazolam. The latter is conjugated to the glucuronide form, and it has only minimal biological activity. Midazolam is excreted primarily by the kidney. Its half-life in children over 12 months is reported to be 0.8 to 1.8 hours, with a clearance of 4.7 to 19.7 ml/min/kg. Doses given to children must be calculated on a mg/kg basis. For children 6 months to 5 years of age the initial dose is 0.05 to 0.1 mg/kg. A total dose up to 0.6 mg/kg titrated slowly may be necessary to achieve the desired endpoint. For children 6 to 12 years of age the initial dose is 0.025 to 0.05 mg/kg with a total dose up to 0.4 mg/kg to achieve the desired end-point.
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              Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients.

              To determine the pharmacokinetics and metabolism of midazolam in pediatric intensive care patients. Prospective population pharmacokinetic study. Pediatric intensive care unit. Twenty-one pediatric intensive care patients aged between 2 days and 17 yrs. The pharmacokinetics of midazolam and metabolites were determined during and after a continuous infusion of midazolam (0.05-0.4 mg/kg/hr) for 3.8 hrs to 25 days administered for conscious sedation. Blood samples were taken at different times during and after midazolam infusion for determination of midazolam, 1-OH-midazolam, and 1-OH-midazolam-glucuronide concentrations via high-performance liquid chromatography-ultraviolet detection. A population analysis was conducted via a two-compartment pharmacokinetic model by the NPEM program. The final population model was used to generate individual Bayesian posterior pharmacokinetic parameter estimates. Total body clearance, apparent volume distribution in terminal phase, and plasma elimination half-life were (mean +/- sd, n = 18): 5.0 +/- 3.9 mL/kg/min, 1.7 +/- 1.1 L/kg, and 5.5 +/- 3.5 hrs, respectively. The mean 1-OH-midazolam/midazolam ratio and (1-OH-midazolam + 1-OH-midazolam-glucuronide)/midazolam ratio were 0.14 +/- 0.21 and 1.4 +/- 1.1, respectively. Data from three patients with renal failure, hepatic failure, and concomitant erythromycin-fentanyl therapy were excluded from the final pharmacokinetic analysis. We describe population and individual midazolam pharmacokinetic parameter estimates in pediatric intensive care patients by using a population modeling approach. Lower midazolam elimination was observed in comparison to other studies in pediatric intensive care patients, probably as a result of differences in study design and patient differences such as age and disease state. Covariates such as renal failure, hepatic failure, and concomitant administration of CYP3A inhibitors are important predictors of altered midazolam and metabolite pharmacokinetics in pediatric intensive care patients. The derived population model can be useful for future dose optimization and Bayesian individualization.
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2015
                02 July 2015
                : 11
                : 1035-1041
                Affiliations
                [1 ]Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Poznan, Poland
                [2 ]Department of Pediatric Radiology, Poznan University of Medical Sciences, Poznan, Poland
                [3 ]Department of Anesthesiology and Intensive Care, Pediatric Intensive Care Unit, Wroclaw Medical University, Wroclaw, Poland
                Author notes
                Correspondence: Alicja Bartkowska-Śniatkowska, Department of Pediatric Anesthesiology and Intensive Therapy, Poznan University of Medical Sciences, Szpitalna, Street 27/33, Poznan 60-572, Poland, Tel +48 61 849 1478, Fax +48 61 849 1486, Email asniatko@ 123456ump.edu.pl
                Article
                tcrm-11-1035
                10.2147/TCRM.S79419
                4494631
                64ae6dec-ea01-4e3b-bd7a-589676a52305
                © 2015 Bartkowska-Śniatkowska et al. This work is published by Dove Medical Press Limited, and licensed under Creative Commons Attribution – Non Commercial (unported, v3.0) License

                The full terms of the License are available at http://creativecommons.org/licenses/by-nc/3.0/. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

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                Categories
                Review

                Medicine
                ceftriaxone,pharmacodynamics,neonate,pseudolithiasis,efficacy
                Medicine
                ceftriaxone, pharmacodynamics, neonate, pseudolithiasis, efficacy

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