• carbapenem-resistant gram-negative bacteria
• clinical efficacy
• microbial efficacy
• polymyxin B
• stroke-associated pneumonia

• Animals
• Humans
• Anti-Bacterial Agents/adverse effects
• Critical Illness
• Antioxidants
• Artificial Intelligence
• Acute Kidney Injury/chemically induced
• Acute Kidney Injury/drug therapy
• Acute Kidney Injury/prevention & control
• Risk Factors
• Intensive Care Units
• Retrospective Studies

• U01 DK130010 NIDDK NIH HHS

• Acute kidney injury
• Medication errors
• Patient harm
• Patient safety
• Pharmacovigilance

• Adult
• Humans
• Retrospective Studies
• Pharmacovigilance
• Acute Kidney Injury/chemically induced
• Acute Kidney Injury/diagnosis
• Kidney
• Kidney Function Tests
• Creatinine

• R01 DK121730 NIDDK NIH HHS

• Epithelial lining fluid
• LC-MS/MS
• Plasma
• Polymyxin B
• Therapeutic drug monitoring

Polymyxin-induced nephrotoxicity is a major safety concern in clinical practice due to long-term adverse outcomes and high mortality.

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.

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.

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.

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.

• Polymyxins
• Nephrotoxicity
• Critically ill adult patients
• Risk factors
• Meta-analysis

Polymyxin B (PMB) is the final option for treating multidrug-resistant Gram-negative bacterial infections. The acceptable pharmacokinetic/pharmacodynamic target is an area under the concentration–time curve across 24 h at a steady state (AUC_ss,24h) of 50–100 mg·h/L. The limited sampling strategy (LSS) is useful for predicting AUC values. However, establishing an LSS is a time-consuming process requiring a relatively dense sampling of patients. Further, given the variability among different centers, the predictability of LSSs is frequently questioned when it is extrapolated to other clinical centers. Currently, limited data are available on a reliable PMB LSS for estimating AUC_ss,24h. This study assessed and validated the practicability of LSSs established in the literature based on data from our center to provide reliable and ready-made PMB LSSs for laboratories performing therapeutic drug monitoring (TDM) of PMB. The influence of infusion and sampling time errors on predictability was also explored to obtain the optimal time points for routine PMB TDM. Using multiple regression analysis, PMB LSSs were generated from a model group of 20 patients. A validation group (10 patients) was used to validate the established LSSs. PMB LSSs from two published studies were validated using a dataset of 30 patients from our center. A population pharmacokinetic model was established to simulate the individual plasma concentration profiles for each infusion and sampling time error regimen. Pharmacokinetic data obtained from the 30 patients were fitted to a two-compartment model. Infusion and sampling time errors observed in real-world clinical practice could considerably affect the predictability of PMB LSSs. Moreover, we identified specific LSSs to be superior in predicting PMB AUC_ss,24h based on different infusion times. We also discovered that sampling time error should be controlled within −10 to 15 min to obtain better predictability. The present study provides validated PMB LSSs that can more accurately predict PMB AUC_ss,24h in routine clinical practice, facilitating PMB TDM in other laboratories and pharmacokinetics/pharmacodynamics-based clinical studies in the future.

• AUCss,24 h threshold
• Efficacy
• Nephrotoxicity
• Polymyxin B
• Therapeutic drug monitoring