Target attainment of cefotaxime in critically ill children with meningococcal septic shock as a model for cefotaxime dosing in severe pediatric sepsis

Autor: Stan J. F. Hartman, Birgit C. P. Koch, Navin P. Boeddha, Gertjan J. Driessen, Rogier Donders, Ebru Ekinci, Saskia N. de Wildt, Jan A. Hazelzet
Přispěvatelé: Pediatrics, Pharmacy, Public Health, Pediatric Surgery
Rok vydání: 2019
Předmět:
Male
0301 basic medicine
Microbiology (medical)
medicine.medical_specialty
Cefotaxime
Adolescent
medicine.drug_class
Critically ill children
Critical Illness
030106 microbiology
Antibiotics
Cephalosporin
Pilot Projects
Neisseria meningitidis
medicine.disease_cause
Sepsis
03 medical and health sciences
All institutes and research themes of the Radboud University Medical Center
0302 clinical medicine
Internal medicine
Streptococcus pneumoniae
medicine
Humans
Pharmacokinetics
030212 general & internal medicine
Child
business.industry
Septic shock
Other Research Radboud Institute for Health Sciences [Radboudumc 0]
Infant
Newborn
Infant
General Medicine
medicine.disease
Shock
Septic
Anti-Bacterial Agents
3. Good health
Meningococcal Infections
Infectious Diseases
Staphylococcus aureus
Child
Preschool
Original Article
Female
Target attainment
Renal disorders Radboud Institute for Health Sciences [Radboudumc 11]
business
medicine.drug
Zdroj: European Journal of Clinical Microbiology and Infectious Diseases, 38, 7, pp. 1255-1260
European Journal of Clinical Microbiology and Infectious Diseases, 38, 1255-1260
European Journal of Clinical Microbiology & Infectious Diseases, 38(7), 1255-1260. Springer-Verlag
European Journal of Clinical Microbiology & Infectious Diseases
ISSN: 1435-4373
0934-9723
1255-1260
DOI: 10.1007/s10096-019-03535-w
Popis: Reduced target attainment of β-lactam antibiotics is reported in critically ill patients. However, as target attainment of cefotaxime in severely ill pediatric sepsis patients may differ from adults due to age-related variation in pharmacokinetics, we aimed to assess target attainment of cefotaxime in this pilot study using meningococcal septic shock patients as a model for severe sepsis. Secondary analysis of prospectively collected data from a randomized controlled trial. Children with meningococcal septic shock (1 month to 18 years) included in this study received cefotaxime 100-150 mg/kg/day as antibiotic treatment. Left-over plasma samples were analyzed using LC-MS/MS to determine cefotaxime concentrations. MIC values from EUCAST were used to determine target attainment of cefotaxime for Neisseria meningitidis (0.125 mg/l), but also for Streptococcus pneumoniae (0.5 mg/l), Enterobacteriaceae (1 mg/l), and Staphylococcus aureus (4 mg/l). Target attainment was adequate when all samples exceeded MIC or fourfold MIC values. One thirty-six plasma samples of 37 severe septic shock patients were analyzed for cefotaxime concentrations. Median age was 2 years with a median PRISM-score of 24 and mortality of 24.8%. The median unbound cefotaxime concentration was 4.8 mg/l (range 0-48.7). Target attainment ranged from 94.6% for the MIC of N. meningitidis to 16.2% for fourfold the MIC S. aureus. Creatinine levels were significantly correlated with cefotaxime levels. Target attainment of cefotaxime with current dosing guidelines seems to be adequate for N. meningitidis but seems to fail for more frequently encountered pathogens in severely ill children.
Databáze: OpenAIRE
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