Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients

Antachopoulos, Charalampos; Ilia, Stavroula; Kadiltzoglou, Paschalis; Baira, Eirini; Dokoumetzidis, Aristides; Gikas, Evagelos; Volakli, Eleni; Σδούγκα, Μαρία; Briassoulis, George; Roilides, Emmanuel

doi:10.1128/aac.02462-17

Cited by 7 publications

(5 citation statements)

References 15 publications

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“…2 case-reports and 1 pharmacometric model were available for daptomycin that included PK parameters [67][68][69]. Both patients in the case reports suffered from cardiac problems, a 13 year old boy with endocarditis [67] and a 8 year old girl with multi-organ failure (including renal insufficiency) awaiting heart transplantation [68].…”

Section: Daptomycinmentioning

confidence: 99%

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Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

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Background Pharmacokinetics (PK) are severely altered in critically ill patients due to changes in volume of distribution (Vd) and/or drug clearance (Cl). This affects the target attainment of antibiotics in critically ill children. We aimed to identify gaps in current knowledge and to compare published PK parameters and target attainment of antibiotics in critically ill children to healthy children and critically ill adults. Methods Systematic literature search in PubMed, EMBASE and Web of Science. Articles were labelled as relevant when they included information on PK of antibiotics in critically ill, non-neonatal, pediatric patients. Extracted PK-parameters included Vd, Cl, (trough) concentrations, AUC, probability of target attainment, and elimination half-life. Results 50 relevant articles were identified. Studies focusing on vancomycin were most prevalent (17/50). Other studies included data on penicillins, cephalosporins, carbapenems and aminoglycosides, but data on ceftriaxone, ceftazidime, penicillin and metronidazole could not be found. Critically ill children generally show a higher Cl and larger Vd than healthy children and critically ill adults. Reduced target-attainment was described in critically ill children for multiple antibiotics, including amoxicillin, piperacillin, cefotaxime, vancomycin, gentamicin, teicoplanin, amikacin and daptomycin. 38/50 articles included information on both Vd and Cl, but a dosing advice was given in only 22 articles. Conclusion The majority of studies focus on agents where TDM is applied, while other antibiotics lack data altogether. The larger Vd and higher Cl in critically ill children might warrant a higher dose or extended infusions of antibiotics in this patient population to increase target-attainment. Studies frequently fail to provide a dosing advice for this patient population, even if the necessary information is available. Our study shows gaps in current knowledge and encourages future researchers to provide dosing advice for special populations whenever possible.

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Section: Daptomycinmentioning

confidence: 99%

“…t½ in steady state was 4.58 h, with an AUC of 594 mg/l/h. The pharmacometric model by Antachopoulos included data of 4 patients aged from 8 to 14 years old with mixed disease conditions in their one compartment model [69]. On the first day of treatment, 3 of the 4 patients met pediatric criteria for sepsis.…”

Section: Daptomycinmentioning

confidence: 99%

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

et al. 2019

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“…Finally, we also found a few PK studies describing linezolid [102], ciprofloxacin [103], and daptomycin [104][105][106] PK in critically ill children (Table 3). [104] CL in sepsis patients is double the CL in non-critically ill children [104] Children with sepsis showed suboptimal AUC values, even with increased dosing. This was even more pronounced in the burn patient.…”

Section: Critical Illness Related Pharmacokinetic Alterations In Children and Infantsmentioning

confidence: 84%

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

et al. 2021

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Children show important developmental and maturational changes, which may contribute greatly to pharmacokinetic (PK) variability observed in pediatric patients. These PK alterations are further enhanced by disease-related, non-maturational factors. Specific to the intensive care setting, such factors include critical illness, inflammatory status, augmented renal clearance (ARC), as well as therapeutic interventions (e.g., extracorporeal organ support systems or whole-body hypothermia [WBH]). This narrative review illustrates the relevance of both maturational and non-maturational changes in absorption, distribution, metabolism, and excretion (ADME) applied to antibiotics. It hereby provides a focused assessment of the available literature on the impact of critical illness—in general, and in specific subpopulations (ARC, extracorporeal organ support systems, WBH)—on PK and potential underexposure in children and neonates. Overall, literature discussing antibiotic PK alterations in pediatric intensive care is scarce. Most studies describe antibiotics commonly monitored in clinical practice such as vancomycin and aminoglycosides. Because of the large PK variability, therapeutic drug monitoring, further extended to other antibiotics, and integration of model-informed precision dosing in clinical practice are suggested to optimise antibiotic dose and exposure in each newborn, infant, or child during intensive care.

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“…Daptomycin could also be used in the treatment of children with MRSA infection [ 24 ], but little is known regarding its pharmacokinetics in critically ill children. Although a research [ 25 ] demonstrated comparable drug levels in pediatric septic patients compared with healthy volunteers and patients with milder infections, the study was based on a small number of patients and the results should be interpreted with caution.…”

Section: Discussionmentioning

confidence: 99%

Multi-site infection by methicillin-resistant Staphylococcus aureus in a six-year old girl: a case report

et al. 2022

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Background Community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging pathogen that leads to severe outcomes, especially in pediatric patients with multiple sites infection. Case presentation We report a case of multiple sites and life-threatening infection caused by CA-MRSA in a 6-year-old girl who manifested sepsis, myelitis, purulent arthritis, purulent meningitis, hydropericardium, pneumonia, and empyema. The girl exhibited good response to the combination therapy of linezolid and rifampicin after treatment failure of vancomycin with maximum dose due to its serum concentration unable to reach therapeutic goal. We performed pleural effusion and hydropericardium effusion drainage and treated left lower limb infection using interdisciplinary approaches. Conclusion This case highlights the need to be aware of CA-MRSA infection, which requires accurate diagnosis, identification of infected sites, appropriate antibiotic treatment, and surgical debridement.

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Pharmacokinetics of Daptomycin in Critically Ill Pediatric Patients

Cited by 7 publications

References 15 publications

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Pharmacokinetics and Target Attainment of Antibiotics in Critically Ill Children: A Systematic Review of Current Literature

Pharmacokinetics of Antibiotics in Pediatric Intensive Care: Fostering Variability to Attain Precision Medicine

Multi-site infection by methicillin-resistant Staphylococcus aureus in a six-year old girl: a case report

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