Correlation between the drug concentration of polymyxin B and polymyxin B‐associated acute kidney injury in critically ill patients: A prospective study

Abstract

In recent years, polymyxin B-associated acute kidney injury (PB-AKI) in critically ill patients has been reported frequently, but polymyxin B (PB) is mainly cleared through non-renal pathways, and the reasons of PB-AKI remain unclear. The aim of this study was to investigate the relationship between the serum concentration of PB and PB-AKI. We conducted a prospective cohort study in an intensive care unit between May 2019 and July 2021. Over the study period, 52 patients were included and divided into an AKI group (n = 26) and a non-AKI group (n = 26). The loading dose of PB in the AKI group was significantly higher than that in the non-AKI group. The C 1/2 , C min , and estimated area under the concentration-time curve (AUC) 0-24 of PB in the AKI group were dramatically increased compared with those in the non-AKI group, but the C max between the two groups showed no differences. Upon obtaining the ROC curve, the areas for the C 1/2 , C min , and estimated AUC 0-24 were 0.742, 0.710, and 0.710, respectively. The sensitivity was ascertained to be 61.54%, and the specificity was 76.92% when the cutoff value for the estimated AUC 0-24 of 97.72 mg•h/L was used preferentially. The incidence of PB-AKI is high and related to the loading dose of PB. PB-AKI could be predicted when the estimated AUC 0-24 of PB was greater than 97.72 mg•h/L.

Comparative pharmacokinetics of polymyxin B in critically ill elderly patients with extensively drug-resistant gram-negative bacteria infections

“…Similarly to our study, Wang et al found that the mean AUC ss, 24 h of PMB in their renal insufficiency group was higher than in their normal renal function group, with marginal significance ( Wang et al, 2021a ). Moreover, some clinical studies have demonstrated that the patients with PMB-associated AKI had higher AUC ss, 0–24 h ( Xu et al, 2022 ; Yang et al, 2022 ), higher baseline serum creatinine levels, or lower baseline glomerular filtration rates compared to patients without PMB-associated nephrotoxicity ( John et al, 2017 ; Xi et al, 2022 ; Xu et al, 2022 ). These results support the speculation that patients with renal dysfunction are more likely to develop higher PMB exposure and that the dosing regimen of PMB should be adjusted in patients with renal dysfunction.…”

Efficacy and Safety Factors Related to Plasma Concentration-Optimized Polymyxin B Therapy in Treating Carbapenem-Resistant Gram-Negative Bacterial Infections in China

“…The AUC thresholds for PMB-associated AKI have been reported to be 99.4 mg h/L 11 and 97.72 mg h/L. 46 Maintaining PMB C min < 3.13 mg/L may help to reduce the occurrence of PMB-associated nephrotoxicity. 47 Here, the risk of AKI was predicted to increase in combined PMB therapy when C min ≥ 2.3 µg /mL and AUC ≥ 82.0 mg h/L, much lower than the thresholds reported previously; this may be related to the higher proportion of older patients in our study population.…”