Greater optimisation of pharmacokinetic/pharmacodynamic parameters through a loading dose of intravenous colistin in paediatric patients

No increased acute kidney injury rate through giving an intravenous colistin loading dose in pediatric patients

“…Nephrotoxicity is known to be a common adverse drug reaction caused by colistin, with a variety of associated conditions, such as cylindruria, hematuria, proteinuria, and elevated blood urea nitrogen or serum creatinine (Falagas et al, 2009b). However, nephrotoxicity reported in the literature is mostly based on SCrassociated criteria, including elevation of SCr and a decline in creatinine clearance or eGFR (Falagas et al, 2009a;Kapoor et al, 2013;Karbuz et al, 2014;Karli et al, 2013;Paksu et al, 2012; Sahbudak Bal et al, 2018;Tamma et al, 2013;Wacharachaisurapol et al, 2020). In this study, we reported nephrotoxicity as AKI defined according to the KDIGO SCr criteria.…”

“…The overall AKI rate within the 1st week after colistin initiation fell from 20.4% to 12.8%. Concerning the ARC effect on antibiotic levels, the colistin dose recommended by the manufacturer (no loading dose recommended) (US FDA, 2017) for pediatric patients may not be adequate, especially in a setting with a high prevalence of MDR-GNB with increased colistin MIC (Ooi et al, 2019;Wacharachaisurapol et al, 2020), as in our setting. Even though the MIC distribution in our study showed that all 24 isolates with colistin MIC results were colistin-susceptible, based on a susceptibility breakpoint of 2 mg/L, as recommended by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (Tsuji et al, 2019), 37.5% were on the cut-off.…”

“…Karageorgos et al conducted a systematic review on intravenous colistin use for infections due to MDR-GNB in critically ill pediatric patients, and suggested that the absence of a loading dose may have an association with mortality (Karageorgos et al, 2019). From our previous pharmacokinetic study of intravenous colistin, the median C average after giving a loading dose reached the desired level of !2 mg/L, which improved drug exposure (Wacharachaisurapol et al, 2020).…”

“…ARC can be as high as 10-67% in critically ill pediatric patients (Huttner et al, 2015;van den Anker et al, 2017;Van Der Heggen et al, 2019). The effects of ARC could be a cause of falsely high AKI rates and low plasma antibiotic concentrations (Huttner et al, 2015;van den Anker et al, 2017;Van Der Heggen et al, 2019;Wacharachaisurapol et al, 2020), as well as ARC-enhanced excretion of serum creatinine and drugs as compared with the baseline owing to glomerular hyperfiltration. The definition of AKI according to the KDIGO SCr criteria is based on a comparison of follow-up vs baseline SCr.…”

“…This is hydrolyzed by blood esterases to the active forms (colistin A, B) (Nakwan et al, 2016). Administering a colistin loading dose is essential to achieve a pharmacokinetic/ pharmacodynamic target within 24 h (Nation et al, 2017;Wacharachaisurapol et al, 2020). Nephrotoxicity is a common adverse effect of colistin.…”