Estimation of the area under concentration-time curve of polymyxin B based on limited sampling concentrations in Chinese patients with severe pneumonia

Chen, Wenqian; Liu, Huifang; Wang, Qianlin; Wang, Xiaoxing; Kong, Xudong; Wang, Xiaoxue; Zhang, Xianglin; Zhan, Qingyuan; Li, Pengmei

doi:10.1007/s00228-020-02986-x

Cited by 14 publications

(9 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Unable to estimate AUC, Han et al reported that C 0h > 3.13 mg/L significantly increased the risk of AKI [ 18 ]. According to the limited sampling strategy equation (AUC ss,24 h = 21.323 + 28.189 × C 0h ) [ 29 ], the C 0h value (3.13 mg/L) was equivalent to an AUC ss,24 h of 109.6 mg h/L. These results also supported the rationality of the upper bound of AUC ss,24 h (100 mg h/L).…”

Section: Discussionmentioning

confidence: 59%

“…For antibiotics with AUC/MIC as PK/PD index, AUC better predicts efficacy and toxicity but is more challenging to get in clinical practice than C 0h [ 30 , 31 ]. Several approaches have been proposed to estimate AUC with sparse samples, such as Bayesian method, limited sampling strategy, and Sawchuk–Zaske equation [ 26 , 29 , 32 ]. Using Bayesian approach, we found that C 0h had an apparent relationship with AUC (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

Yang

Liu

et al. 2022

Crit Care

View full text Add to dashboard Cite

Background Evidence supports therapeutic drug monitoring of polymyxin B, but clinical data for establishing an area under the concentration–time curve across 24 h at steady state (AUCss,24 h) threshold are still limited. This study aimed to examine exposure–response/toxicity relationship for polymyxin B to establish an AUCss,24 h threshold in a real-world cohort of patients. Methods Using a validated Bayesian approach to estimate AUCss,24 h from two samples, AUCss,24 h threshold that impacted the risk of polymyxin B-related nephrotoxicity and clinical response were derived by classification and regression tree (CART) analysis and validated by Cox regression analysis and logical regression analysis. Results A total of 393 patients were included; acute kidney injury (AKI) was 29.0%, clinical response was 63.4%, and 30-day all-cause mortality was 35.4%. AUCss,24 h thresholds for AKI of > 99.4 mg h/L and clinical response of > 45.7 mg h/L were derived by CART analysis. Cox and logical regression analyses showed that AUCss,24 h of > 100 mg h/L was a significant predictor of AKI (HR 16.29, 95% CI 8.16–30.25, P < 0.001) and AUCss,24 h of ≥ 50 mg h/L (OR 4.39, 95% CI 2.56–7.47, P < 0.001) was independently associated with clinical response. However, these exposures were not associated with mortality. In addition, the correlation between trough concentration (1.2–2.8 mg/L) with outcomes was similar to AUCss,24 h. Conclusions For critically ill patients, AUCss,24 h threshold of 50–100 mg h/L was associated with decreased nephrotoxicity while assuring clinical efficacy. Therapeutic drug monitoring is recommended for individualizing polymyxin B dosing.

show abstract

Section: Discussionmentioning

confidence: 59%

Section: Discussionmentioning

confidence: 99%

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

Yang

Liu

et al. 2022

Crit Care

View full text Add to dashboard Cite

show abstract

“…The concentration of polymyxin B was determined using ultrahighperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method published previously by our team. 25 The concentration of each sample was defined as the sum of the concentrations of the major components of polymyxin B, including polymyxin B1, B2, B3 and isoleucine-polymyxin B1. The analytes were then eluted on a UPLC BEH (ethylene bridged hybrid) C18 column (50 Â 2.1 mm, 1.8 μm).…”

Section: Drug Assaymentioning

confidence: 99%

The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation

Wang

Chen

et al. 2022

Clinical Pharmacy Therapeu

Self Cite

View full text Add to dashboard Cite

What is known and objective: The presence of extracorporeal membrane oxygenation (ECMO) is suggested to further exacerbate the pharmacokinetics (PK) alterations that occur during critical illness. The objectives of this study were to determine the population PK model of polymyxin B in critically ill patients with or without ECMO support investigated the influence of ECMO on PK variability and to identify an optimal dosing strategy.Methods: Forty-four critically ill patients were enrolled, including eight patients with ECMO support. Eight serial serum samples were collected from each patient at steady state. The population PK was determined using NONMEM and Monte Carlo simulation was performed to evaluate the exposures of different dosing regimens. Results:The PK analyses included 342 steady-state concentrations and a twocompartment model was optimal for polymyxin B PK data modelling. In the final model, creatinine clearance (CL CR ) was the significant covariate on CL (typical value 1.27 L/h; between-subject variability 15.1%) and ECMO did not show a significant impact on the polymyxin B PK. Additionally, we found that the PK parameter estimates of patients with and without ECMO support were mostly similar. Based on Monte Carlo simulations, the dose escalation of polymyxin B in patients with increased CL CR improved the probability of achieving required exposure. For patients with CL CR ≤ 120 ml/min, a dosage regimen of 100 mg every 12 h may represent the optimal regimen at an MIC of 1 mg/L.What is new and conclusion: The impact of ECMO on the polymyxin B PK is likely to be minimal. Our study showed a potential relationship between CL CR and polymyxin B CL, and the dose of polymyxin B should be adjusted in patients with increased CL CR .

show abstract

“…Each dose of polymyxin B (polymyxin B sulfate for injection; 1 mg containing approximately 10 000 U) was administered as a 50‐ml infusion over a 1‐h period. The method used in the previously published literature of our team was used to determine the plasma concentration of polymyxin B and estimate the area under the concentration–time curve across 24 h at steady state (AUC ss,24h ) 17 . For patients with TDM data, we collected the first AUC ss,24h value during the treatment course.…”

Section: Methodsmentioning

confidence: 99%

“…The method used in the previously published literature of our team was used to determine the plasma concentration of polymyxin B and estimate the area under the concentration–time curve across 24 h at steady state (AUC ss,24h ). 17 For patients with TDM data, we collected the first AUC ss,24h value during the treatment course. According to the guideline for optimal use of polymyxins, 10 the target value of AUC ss,24h was set to 50–100 mg h L −1 .…”

Section: Methodsmentioning

confidence: 99%

Effectiveness, nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients

Wang

Chen

et al. 2022

Clinical Respiratory J

Self Cite

View full text Add to dashboard Cite

Objectives We aimed to assess the effectiveness and nephrotoxicity of polymyxin B in critically ill patients with nosocomial pneumonia and to evaluate the utility of its therapeutic drug monitoring (TDM). Methods We retrospectively analyzed patients who received polymyxin B treatment for ≥48 h since the establishment of polymyxin B TDM in a 26‐bed tertiary referral intensive care unit. Univariate and multivariate analyses were conducted to assess the variables associated with polymyxin B effectiveness and nephrotoxicity. Results A total of 62 patients were enrolled. Most (56.5%) of the patients performed TDM, 54.3% of them reached the therapeutic target of area under curve across 24 h at steady state (AUCss,24h) of 50–100 mg h L−1, and 10 patients had an AUCss,24h value of <50 mg h L−1. Thirty‐six (58.1) and 31 (50.0%) patients had favorable clinical and microbiological responses, respectively. Reaching the therapeutic target of AUCss,24h (odds ratio [OR] = 13.15, p = 0.015), a favorable microbiological response (OR = 40.80, p = 0.00), and complicated with septic shock (OR = 0.12, p = 0.021) were independently associated with favorable clinical outcomes of polymyxin B treatment. The incidence of acute kidney injury (AKI) was 45.2%. A lower creatinine clearance (OR = 0.96, p = 0.008) and concomitant treatment with loop diuretics (OR = 5.93, p = 0.046) were predictive of nephrotoxicity. Conclusion Our findings show that TDM of polymyxin B is a valuable intervention, and the achievement of its optimal pharmacodynamic target can improve treatment outcome. Renal insufficiency and concomitant treatment with loop diuretics were found to be associated with the risk of nephrotoxicity.

show abstract

Estimation of the area under concentration-time curve of polymyxin B based on limited sampling concentrations in Chinese patients with severe pneumonia

Cited by 14 publications

References 19 publications

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

An area under the concentration–time curve threshold as a predictor of efficacy and nephrotoxicity for individualizing polymyxin B dosing in patients with carbapenem-resistant gram-negative bacteria

The population pharmacokinetics and dose optimization of polymyxin B in critically ill patients with or without extracorporeal membrane oxygenation

Effectiveness, nephrotoxicity, and therapeutic drug monitoring of polymyxin B in nosocomial pneumonia among critically ill patients

Contact Info

Product

Resources

About