Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients

Deng, Yang; Gu, Junyuan; Li, Xin; Tong, Huan; Guo, Siwei; Xu, Bing; Li, You; Zhang, Bikui; Liu, Ying; Huang, Haiying; Xiao, Gui-Ying

doi:10.1007/s40121-022-00655-3

Cited by 6 publications

(7 citation statements)

References 60 publications

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“…In addition, the combined predictor based on WBC count and AUC 1/2t,max was an excellent predictor of AKI in critically ill patients, with an AUROC of 0.805, which is similar to that of the final models of Han et al (0.813) and Deng et al (0.799). 16 , 17 A combined predictor value of >0.57 suggests that the patient was at a higher risk of developing AKI.…”

Section: Discussionmentioning

confidence: 99%

“…Han et al 16 reported on the association between PMB plasma concentration and AKI development and suggested that the trough concentration of PMB should be controlled at <3.13 mg/L to reduce the risk of AKI. Interestingly, Deng et al 17 reported that the peak concentration rather than the trough concentration of PMB and PMB1 is a significant predictor for the development of AKI. If the peak concentration of PMB1 was >5.23 mg/ml, the probability of AKI would be >50%.…”

Section: Introductionmentioning

confidence: 99%

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Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

Wang,

Li,

Huang

et al. 2023

CPT Pharmacom & Syst Pharma

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This study aimed to evaluate the association between polymyxin B (PMB) exposure and acute kidney injury (AKI) and analyze the risk factors for PMB‐induced AKI in critically ill patients. Plasma concentrations of PMB were determined using an ultra‐performance liquid chromatography‐tandem mass spectrometer in intensive care unit patients who were administered PMB. Univariate and multivariate analyses were conducted to identify risk factors. A receiver operating characteristic curve was constructed to assess the discriminant power of the factors and to identify the cut‐off value for AKI. The white blood cell count and estimated area under the concentration–time curve (AUC) of patients administered PMB were independent risk factors for PMB‐induced AKI, where AUC were calculated using a first‐order pharmacokinetic equation based on the mid‐dosing interval concentration (C1/2t) and peak concentration. The area under the receiver operating characteristic curve of the final model was 0.805 (95% confidence interval 0.690–0.921). The cut‐off value for the combined predictor was 0.57. Alternatively, when using C1/2t, which was strongly correlated with AUC, as the only independent risk factor, the analysis showed that the 3.47 μg/mL threshold provides favorable differentiation between the AKI and non‐AKI groups. These results provide insightful information for TDM‐guiding PMB dosing in the clinical practice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

Wang,

Li,

Huang

et al. 2023

CPT Pharmacom & Syst Pharma

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“…Polymyxins are bactericidal drugs that encompass a variety of chemicals. They were generated from Paenibacillus polymyxa and were clinically useful in the 1950s [ 5 ]. However, because of their toxic effects and the accessibility of those other safer and more efficient antibacterial medications, their uses have declined significantly since the 1970s [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative study of polymyxin B and colistin sulfate in the treatment of severe comorbid patients infected with CR-GNB

et al. 2023

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Background With the difficulties in choosing colistin sulfate and polymyxin B sulfate (PBS) for carbapenem-resistant gram-negative bacteria (CR-GNB), we compared the efficacy and safety of these two old polymyxins in treatment of critically ill patients infected with CR-GNB infection. Methods One hundred four patients infected with CR-GNB in ICU were retrospectively grouped by PBS (68 patients) or colistin sulfate (36 patients). Clinical efficacy including symptoms, inflammatory parameters, defervescence, prognosis and microbial efficacy were analyzed. Hepatotoxicity, nephrotoxicity, and hematotoxicity were evaluated by TBiL, ALT, AST, creatinine, and thrombocytes. Results Demographic characteristics between colistin sulfate and PBS were not significantly different. Most of the CR-GNB were cultured in respiratory tract (91.7% vs 86.8%), and almost all were polymyxin-sensitive (98.2% vs 100%, MIC ≤ 2 μg/ml). The microbial efficacy in colistin sulfate (57.1%) was significantly higher than PBS (30.8%) (p = 0.022), however, no significant difference in clinical success was seen in both groups (33.8% vs 41.7%), as well as mortality, defervescence, imaging remission, days in the hospital, microbial reinfections, and prognosis, and almost all patients defervesce within 7 days (95.6% vs 89.5%). Conclusions Both polymyxins can be administrated in critically ill patients infected with CR-GNB and colistin sulfate is superior to PBS in microbial clearance. These results highlight the necessity of identifying CR-GNB patients who may benefit from polymyxin and who are at higher risk of mortality.

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“…No popPK studies were established using actual free plasma concentrations of polymyxin B. Since only unbound drug can permeate into target tissues or organs, the pharmacological activity of a drug usually depends on the free concentration in the blood rather than the total drug concentration 14 . Moreover, the significant variation in protein levels among individual critically ill patients results in large differences in the free fraction of polymyxin B 11,15 .…”

mentioning

confidence: 99%

“…Since only unbound drug can permeate into target tissues or organs, the pharmacological activity of a drug usually depends on the free concentration in the blood rather than the total drug concentration. 14 Moreover, the significant variation in protein levels among individual critically ill patients results in large differences in the free fraction of polymyxin B. 11,15 Therefore, the reported popPK studies of polymyxin B cannot reflect the actual therapeutic effect.…”

mentioning

confidence: 99%

Population Pharmacokinetic Modeling Using Polymyxin B Free Plasma Concentrations From Published Reports and Evaluation of Dosage Regimens Based on Monte Carlo Simulation in Critically Ill Patients

Zheng

Chen

et al. 2023

The Journal of Clinical Pharma

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A population pharmacokinetic (pop PK) model of polymyxin B was developed using nonlinear mixed‐effects (NONMEM) modeling based on free plasma concentrations to determine whether dose adjustment is required in critically ill patients. One thousand pharmacokinetic profiles for virtual patients with a body weight of 70 kg were simulated using Monte Carlo simulation at different dose scenarios, and area under the concentration–time curve of free drug (fAUC) was computed. The probability of target attainment (PTA) at each minimum inhibitory concentration (MIC) was calculated using fAUC/MIC as a pharmacokinetic/pharmacodynamic (PK/PD) index. The final population PK model was a 2‐compartment model. PTA showed that 3.5 mg/kg/day regimens of polymyxin B effectively achieved the fAUC/MIC target of 10 (one log10 kill) against Pseudomonas aeruginosa strains with MIC of 1 mg/L or less (PTA, 90.7% or greater), while the dose regimen were ineffective against strains with an MIC of 2 mg/L or greater (PTA, 56.9% or less). For Klebsiella pneumoniae, the fAUC/MIC target of 17.4 (one log10 kill) was achieved in more than 90.4% of cases for MIC of 0.5 mg/L or less with 3 mg/kg/day regimens. However, the PTA decreased dramatically as MICs increased above 1 mg/L (PTA, 56.1% or less). The polymyxin B dosage regimen of 3.5 mg/kg/day and 3 mg/kg/day are sufficient to treat P. aeruginosa infections with an MIC of 1 mg/L or less and K. pneumoniae infections with an MIC of 0.5 mg/L or less, respectively. The current recommended dose (1.5–3 mg/kg/day) of polymyxin B appears inadequate to attain the PK/PD target for therapeutic efficacy against infections caused by P. aeruginosa and K. pneumoniae isolates when MIC is above the values.

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Does Monitoring Total and Free Polymyxin B1 Plasma Concentrations Predict Polymyxin B-Induced Nephrotoxicity? A Retrospective Study in Critically Ill Patients

Cited by 6 publications

References 60 publications

Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

Mid‐dosing interval concentration is important for polymyxin B exposure and acute kidney injury in critically ill patients

Comparative study of polymyxin B and colistin sulfate in the treatment of severe comorbid patients infected with CR-GNB

Population Pharmacokinetic Modeling Using Polymyxin B Free Plasma Concentrations From Published Reports and Evaluation of Dosage Regimens Based on Monte Carlo Simulation in Critically Ill Patients

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