Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center

Abstract

Aims and objectivesVancomycin is a drug of choice for various gram-positive bacterial (GPB) infections and is largely prescribed to pediatric intensive care unit (PICU) patients. Despite the different pathophysiology of these patients, limited data are available on pharmacokinetics of vancomycin. There are lack of data for critically ill Indian children; hence, study was conducted to assess the steady-state pharmacokinetics in children admitted to PICU.Materials and methodsTwelve subjects (seven males, five females) aged 1–12 years were enrolled. Vancomycin (dose of 20 mg/kg per 8 hours) was infused for over 1 hour and steady-state pharmacokinetics was performed on day 3. Vancomycin concentrations were measured by the validated liquid chromatography mass spectrometry method. Pharmacokinetic parameters were calculated using Winnonlin (Version 6.3; Pharsight, St. Louis, MO).ResultsThe steady-state mean Cssmax was 40.94 μg/mL (±15.07), and mean AUC0–8 hours was 124.15 μg/mL (±51.27). The mean t1/2 was 4.82 hours (±2.71), Vd was 12.48 L (±4.43), and Cl was 2.08 mL/minute (±0.89). The mean AUC0–24 among 12 subjects was 372.44 μg/mL (±153.82). Among 35 measured trough concentrations, 23 (65.71%) were below, 11 (31.43%) were within, and 1 (2.86%) was above the recommended range.ConclusionThe pharmacokinetic parameters of vancomycin were comparable with previously reported studies. However, recommended trough levels (10–20 μg/mL) were not achievable with current recommended dosing of 60 mg/kg/day.How to cite this articleMali NB, Tullu MS, Wandalkar PP, Deshpande SP, Ingale VC, Deshmukh CT, et al. Steady-state Pharmacokinetics of Vancomycin in Children Admitted to Pediatric Intensive Care Unit of a Tertiary Referral Center. IJCCM 2019;23(11):497–502.

Pharmacokinetics of Vancomycin in Critically Ill Children: A Systematic Review

“…Six studies analysed data from less than 30 children [ 3 , 25 , 26 , 29 – 31 ], while one study included 250 children [ 23 ]. Six studies recruited between 30 and 100 patients [ 20 – 22 , 24 , 27 , 28 ].…”

“…The serum creatinine of the patients in the studies ranged between 8.84 and 65.42 μmol/L [ 20 – 23 , 25 – 28 , 30 ] (Table 1 ). Creatinine clearance (CL CR ) was between 7.8 and 164.1 mL/min/1.73 m 2 [ 3 , 20 , 21 , 23 , 25 – 29 ], with very low CL CR observed in the study by Zane et al [ 20 ]. Patients with AKI and RRT in the study by Zylbersztajn et al [ 26 ] had low CL CR compared to patients with only AKI.…”

“…Blood sampling was done after a steady state was achieved in eight studies [ 3 , 22 , 23 , 26 – 30 ]. In those studies, the steady state was variously defined as after the third dose [ 22 , 30 ], after the fourth dose [ 27 – 29 ], after 30 h [ 29 ], or after 48 h [ 3 , 22 , 26 ]. In one study, blood was collected after the first dose and after the third dose [ 20 ].…”

“…They also collected trough concentrations immediately before the fifth dose. Mali et al [ 3 ] collected the first blood samples 48 h after the first infusion (baseline), with other samples collected at 1, 1.25, 1.5, 2, 2.5, 3, and 6 h and at 72 h from baseline. Gous et al [ 30 ] collected blood samples immediately before vancomycin infusion and at 30, 60, 120 and 300 min after infusion on days 3 and 9 after the first vancomycin infusion.…”

“…Vancomycin is a tricyclic glycopeptide antibiotic that has been used extensively in adult [ 1 , 2 ] and paediatric [ 3 , 4 ] intensive care unit patients for the treatment of infections with Gram-positive organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and penicillin-resistant Streptococcus pneumoniae . It is also frequently used in the context of hospital-acquired infections (including ventilator-associated pneumonia and wound sepsis) while awaiting the identification of specific microorganisms.…”