Neonatal Infections are among the most common reasons for admission to the intensive care unit. Neonatal sepsis (NS) significantly contributes to mortality rates. Empiric antibiotic therapy of NS recommended by current international guidelines includes benzylpenicillin, ampicillin/amoxicillin, and aminoglycosides (gentamicin). The rise of antibacterial resistance precipitates the growth of the use of antibiotics of the Watch (second, third, and fourth generations of cephalosporines, carbapenems, macrolides, glycopeptides, rifamycins, fluoroquinolones) and Reserve groups (fifth generation of cephalosporines, oxazolidinones, lipoglycopeptides, fosfomycin), which are associated with a less clinical experience and higher risks of toxic reactions. A proper dosing regimen is essential for effective and safe antibiotic therapy, but its choice in neonates is complicated with high variability in the maturation of organ systems affecting drug absorption, distribution, metabolism, and excretion. Changes in antibiotic pharmacokinetic parameters result in altered efficacy and safety. Population pharmacokinetics can help to prognosis outcomes of antibiotic therapy, but it should be considered that the neonatal population is heterogeneous, and this heterogeneity is mainly determined by gestational and postnatal age. Preterm neonates are common in clinical practice, and due to the different physiology compared to the full terms, constitute a specific neonatal subpopulation. The objective of this review is to summarize the evidence about the developmental changes (specific for preterm and full-term infants, separately) of pharmacokinetic parameters of antibiotics used in neonatal intensive care units.
Infections are important factors contributing to the morbidity and mortality among elderly patients. High rates of consumption of antimicrobial agents by the elderly may result in increased risk of toxic reactions, deteriorating functions of various organs and systems and leading to the prolongation of hospital stay, admission to the intensive care unit, disability, and lethal outcome. Both safety and efficacy of antibiotics are determined by the values of their plasma concentrations, widely affected by physiologic and pathologic age-related changes specific for the elderly population. Drug absorption, distribution, metabolism, and excretion are altered in different extents depending on functional and morphological changes in the cardiovascular system, gastrointestinal tract, liver, and kidneys. Water and fat content, skeletal muscle mass, nutritional status, use of concomitant drugs are other determinants of pharmacokinetics changes observed in the elderly. The choice of a proper dosing regimen is essential to provide effective and safe antibiotic therapy in terms of attainment of certain pharmacodynamic targets. The objective of this review is to perform a structure of evidence on the age-related changes contributing to the alteration of pharmacokinetic parameters in the elderly.
Íà äàííûé ìîìåíò ïðîáëåìà àíòèáèîòèêîðåçèñòåíòíîñòè ÿâëÿåòñÿ îäíîé èç ñàìûõ àêòóàëüíûõ. Ýôôåêòèâíîñòü àíòèáàêòåðèàëüíîé òåðàïèè îïðåäåëÿåòñÿ, â òîì ÷èñëå, è ôàðìàêîêèíåòè÷åñêèìè õàðàêòåðèñòèêàìè àíòèáàêòåðèàëüíîãî ïðåïàðàòà. Òåðàïåâòè÷åñêèé ëåêàðñòâåííûé ìîíèòîðèíã (ÒËÌ) ÿâëÿåòñÿ ñîâðåìåííûì ñïîñîáîì ïðåîäîëåíèÿ óñòîé÷èâîñòè âîçáóäèòåëåé â óñëîâèÿõ ñòàöèîíàðà, êîòîðûé ïîçâîëÿåò èíäèâèäóàëèçèðîâàòü äîçû ïðåïàðàòà, îñîáåííî ó ñëîaeíûõ ïàöèåíòîâ ïðè ïîâûøåííîé ðåçèñòåíòíîñòè âîçáóäèòåëåé.  ñòàòüå îïèñàíû äâà êëèíè÷åñêèõ ñëó÷àÿ íàçíà÷åíèÿ ìåðîïåíåìà è ïðîâåäåíèÿ ÒËÌ, ÷òî ïîçâîëèëî èíäèâèäóàëèçèðîâàòü äîçèðîâêè àíòèáàêòåðèàëüíîãî ïðåïàðàòà è îáåñïå÷èòü àäåêâàòíóþ è ýôôåêòèâíóþ òåðàïèþ ïàöèåíòàì.  îïèñàííûõ êëèíè÷åñêèõ ñëó÷àÿõ ïðåäëîaeåííûé ðåaeèì äîçèðîâàíèÿ ìåðîïåíåìà ïîçâîëèë äîñòè÷ü öåëåâûõ çíà÷åíèé ïîêàçàòåëÿ % T> ÌÏÊ -áîëåå 40%. Êëþ÷åâûå ñëîâà: ìåðîïåíåì, àíòèáàêòåðèàëüíàÿ òåðàïèÿ, òåðàïåâòè÷åñêèé ëåêàðñòâåííûé ìîíèòîðèíã.Antibiotic resistance is one of the most relevant problems nowadays. The effectiveness of antibiotic therapy is determined, among other things, by the pharmacokinetic characteristics of the antibacterial drug. Therapeutic drug monitoring (TDM) is a modern way of overcoming the resistance of pathogens found in hospitals, which allows individualizing doses of the drug, especially in complex cases with increased pathogen resistance. The article describes two clinical cases of prescribing meropenem and conducting TDM, which made it possible to individualize the dosage of the antibacterial drug and provide adequate and effective therapy to patients. In the described clinical cases, the proposed dosing regimen of meropenem allowed achieving the target values of % T> MIC -more than 40%.
This article describes the clinical case of acute gangrenous appendicitis in a pregnant woman, followed by antibiotic therapy with meropenem dose of 2 g I. V. q8h with therapeutic drug monitoring (TDM) management. Therapeutic drug monitoring may be helpful for special patient populations with large pharmacokinetic variability, which include pregnant women. The goal of therapeutic drug monitoring is to increase the effectiveness of therapy by adjusting the dose and dosage regimen, as well as reducing the likelihood of side effects.
Convulsions in full-term and especially in premature newborns are observable pathologies. Selection of anticonvulsant therapy is very difficult: newborns have particular pharmacokinetics of drugs, insufficient data on doses and therapeutic concentrations of anticonvulsants in the blood (premature infants mainly). This article is an overview, with an emphasis on the features of dosing and pharmacokinetics of anticonvulsants in term and preterm infants.
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