| Abstract |
Background
Vancomycin is a bactericidal glycopeptide that inhibits peptidoglycan synthesis with activity against Gram positive bacteria. It is considered the drug of choice in the treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in both adult and pediatric population. The interindividual variability of vancomycin in pharmacokinetics necessitates the use of individualized pharmacokinetic model in order to optimize the expected efficacy of vancomycin while minimizing toxicity. The best predictor of treatment efficacy is an area under the curve to minimum inhibitory concentration (AUC/MIC) ≥400. Furthermore, multiple studies have demonstrated the inability to obtain trough levels in the targeted range 10-20μg/ml, especially in critically ill pediatric patients in ICU.
Objective
To assess the pharmacokinetic behavior of vancomycin in children hospitalized in ICU, via a retrospective and a prospective study with two different groups of patients receiving or not a loading dose (LD) of vancomycin. Additionally, we studied whether there is a correlation between measured trough levels and the ratio AUC/MIC calculated by a specific pharmacokinetic model.
Materials and methods
This is a retrospective as well as prospective single-centre study enrolling children who met the inclusion criteria, aged between 3months and 18 years old and received vancomycin during hospitalization in ICU from 2012 to 2018. Epidemiological, clinical and laboratory data were recorded and the AUC/MIC (MIC≤1) ratio was calculated using the pharmacokinetic model proposed by Le et al: CL(L/h)VANCO=0.248*Weight0.75*(0.48/SCr)0.361*(ln(age)/7.8)0.995 and AUC0-24= [total vancomycin (mg) over 24h/CLVANCO . Participants in our prospective study were randomized to receive a LD (30mg/kg) or a conventional initial dose (15mg/kg). These were followed by a 15mg/kg dose every six hours in both groups. Serum vancomycin troughs were measured 12, 24 and 48 hours after the initiation of vancomycin therapy. The data was analyzed using Microsoft EXCEL.
Results
A total of 80 patients were identified for inclusion in the retrospective study. The median of the vancomycin troughs was below the therapeutic range 10-20μg/ml at any time measured (7.64μg/ml at 24h, 6.8μg/ml at 24-48h, 6.61μg/ml at 48-72h and 5.72μg/ml at >72h). On the contrary, the median respective ratio AUC/MIC (MIC≤1) calculated by Le et al ‘s model was greater than 400. No linear correlation was found between the measured troughs and AUC/MIC ratio (r=0.12, p=0.39, P-value<0.05). Our RCT enrolled 10 patients, in which the group with LD achieved therapeutic ratio AUC/MIC≥400 as early as 12 hours after vancomycin therapy was initiated, compared to the group without LD (451.8±104.8 vs 253.9±66.5). Respectively, the group with LD had higher troughs compared to the group without LD (median 8,4 vs 6), though below the therapeutic range according to the guidelines. No linear correlation was found between the measured troughs and AUC/MIC ratio at 12, 24 and 48 hours (r=0.5, p=0.09 at 12h, r=0.09, p=0.79 at 24h and r=0.43, p=0.1 at 48h, P-value<0.05)
Conclusions
In our study, a vancomycin loading dose resulted in earlier achievement of therapeutic ratio AUC/MIC whereas did not result in troughs between the proposed range of 10-20μg/ml according to the guidelines. There was no linear correlation between measured troughs and AUC/MIC ratio.
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Φαρμακοκινητική -Φαρμακοδυναμική μελέτη βανκομυκίνης σε παιδιατρικούς ασθενείς στη ΜΕΘ
