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

Ye, Qinghua; Wang, Qianlin; Chen, Ziying; Chen, Wenqian; Zhan, Qingyuan; Wang, Chen

doi:10.1111/crj.13493

Cited by 8 publications

(4 citation statements)

References 43 publications

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“…These specific physiological features may cause changes in drug pharmacokinetic (PK), such as drug clearance and apparent volume of distribution, which lead to insufficient antibiotics concentrations in sites of infection and are associated with prolonged hospital stay and poor prognosis ( Udy et al, 2013 ). Previous PK/PD studies have shown that the rate of reaching the standard polymyxin B exposure AUC at a typical clinical dose is low, approximately 54.3% ( Ye et al, 2022 ) in critically ill patients. However, the exact causes have never been defined.…”

Section: Introductionmentioning

confidence: 99%

Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients

Liang

Liu²,

Deng³

et al. 2023

Front. Pharmacol.

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Objectives: Since the global broadcast of multidrug-resistant gram-negative bacteria is accelerating, the use of Polymyxin B is sharply increasing, especially in critically ill patients. Unsatisfactory therapeutic effects were obtained because of the abnormal physiological function in critically ill patients. Therefore, the determination of optimal polymyxin B dosage becomes highly urgent. This study aimed to illustrate the polymyxin B pharmacokinetic characteristics by defining the influencing factors and optimizing the dosing regimens to achieve clinical effectiveness.Methods: Steady-state concentrations of polymyxin B from twenty-two critically ill patients were detected by a verified liquid chromatography-tandem mass spectrometry approach. The information on age, weight, serum creatinine, albumin levels, and Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score was also collected. The population PK parameters were calculated by the non-parametric adaptive grid method in Pmetrics software, and the pharmacokinetic/pharmacodynamics target attainment rate was determined by the Monte Carlo simulation method.Results: The central clearance and apparent volume of distribution for polymyxin B were lower in critically ill patients (1.24 ± 0.38 L h-1 and 16.64 ± 12.74 L, respectively). Moreover, albumin (ALB) levels can be used to explain the variability in clearance, and age can be used to describe the variability in the apparent volume of distribution. For maintaining clinical effectiveness and lowering toxicity, 75 mg q12 h is the recommended dosing regimen for most patients suffering from severe infections.Conclusion: This study has clearly defined that in critically ill patients, age and ALB levels are potentially important factors for the PK parameters of polymyxin B. Since older critically ill patients tend to have lower ALB levels, so higher dosages of polymyxin B are necessary for efficacy.

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Section: Introductionmentioning

confidence: 99%

Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients

Liang

Liu²,

Deng³

et al. 2023

Front. Pharmacol.

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“…Previously, we found that AUC ss,24 h of > 100 mg h/L was a good predictor of the probability of nephrotoxicity ( P = 0.001) [ 16 ]. Ye et al found that the therapeutic target of AUC ss,24 h (odds ratio [OR] = 13.15, P = 0.015) was independently associated with favorable clinical outcomes of polymyxin B treatment [ 17 ]. Some studies reported that maintaining a trough concentration (C 0h or C min ) of polymyxin B below 3.13 mg/L or peak concentration (C max ) of polymyxin B1 below 5.23 mg/L might help reduce the incidence of polymyxin B-related nephrotoxicity [ 18 , 19 ].…”

Section: Introductionmentioning

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

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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.

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“…The sample sizes per study ranged from 11 to 4910 critically ill patients. This systematic review and meta-analysis included 3 parallel cohort studies that reported outcome measures associated with colistin and PMB use[ 62 , 76 , 80 ], 2 studies with colistin and PMB use[ 17 , 68 ], 75 studies with colistin use alone[ 16 , 18 - 40 , 42 - 57 , 59 - 61 , 64 - 67 , 70 - 75 , 78 , 81 , 83 - 99 , 101 - 102 , 104 ] and 9 studies with PMB use alone[ 41 , 58 , 63 , 69 , 77 , 79 , 82 , 100 , 103 ]. Regarding the geographical distribution, 35 studies were conducted in Europe, 31 in Asia, 6 in North America, 6 in South America and 4 in Africa.…”

Section: Resultsmentioning

confidence: 99%

Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis

Wang¹,

Xiang²,

Song³

et al. 2022

World J Clin Cases

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BACKGROUND Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality. AIM To conducted a systematic review and meta-analysis of the prevalence and potential predictors of polymyxin-induced nephrotoxicity in adult intensive care unit (ICU) patients. METHODS PubMed, EMBASE, the Cochrane Library and Reference Citation Analysis database were searched for relevant studies from inception through May 30, 2022. The pooled prevalence of polymyxin-induced nephrotoxicity and pooled risk ratios of associated factors were analysed using a random-effects or fixed-effects model by Stata SE ver. 12.1. Additionally, subgroup analyses and meta-regression were conducted to assess heterogeneity. RESULTS A total of 89 studies involving 12234 critically ill adult patients were included in the meta-analysis. The overall pooled incidence of polymyxin-induced nephrotoxicity was 34.8%. The pooled prevalence of colistin-induced nephrotoxicity was not higher than that of polymyxin B (PMB)-induced nephrotoxicity. The subgroup analyses showed that nephrotoxicity was significantly associated with dosing interval, nephrotoxicity criteria, age, publication year, study quality and sample size, which were confirmed in the univariable meta-regression analysis. Nephrotoxicity was significantly increased when the total daily dose was divided into 2 doses but not 3 or 4 doses. Furthermore, older age, the presence of sepsis or septic shock, hypoalbuminemia, and concomitant vancomycin or vasopressor use were independent risk factors for polymyxin-induced nephrotoxicity, while an elevated baseline glomerular filtration rate was a protective factor against colistin-induced nephrotoxicity. CONCLUSION Our findings indicated that the incidence of polymyxin-induced nephrotoxicity among ICU patients was high. It emphasizes the importance of additional efforts to manage ICU patients receiving polymyxins to decrease the risk of adverse outcomes.

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

Cited by 8 publications

References 43 publications

Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients

Population pharmacokinetic analysis and dosing optimization of polymyxin B in critically ill patients

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

Prevalence of polymyxin-induced nephrotoxicity and its predictors in critically ill adult patients: A meta-analysis

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