Differences in Colistin Administration and Bacterial and Treatment Outcomes in Critically Ill Patients

Sunmi Jung,Sandy Jeong Rhie,Eun Sun Son,Eun Kyoung Chung,Min Sun Jun

doi:10.1038/s41598-019-44965-y

Abstract

The desired target steady-state average colistin concentration (Css,avg) to balance between therapeutic effectiveness and nephrotoxicity is largely unclear. The objective of this study was to evaluate the effect of the desired target colistin Css,avg on the effectiveness and safety of IV colistin therapy in critically ill patients. Overall, 153 critically ill patients (71% males) receiving IV colistin were retrospectively analyzed. The desired target colistin Css,avg was estimated based on the daily colistin dose and creatinine clearance of each patient. No significant predictor for clinical cure was identified. However, microbiological outcome was significantly associated with pneumonia compared to bacteremia (odds ratio [OR] 0.092, 95% confidence interval [CI] [0.033–0.251], P < 0.001) and the use of IV colistin loading dose (OR 2.783, 95% CI [1.126–6.880], P = 0.027). Colistin-associated nephrotoxicity was significantly less likely to occur in patients who received inhaled colistin close to the time of IV colistin therapy (OR 0.331, CI [0.119–0.925], P = 0.035). The desired target Css,avg of colistin was not associated with treatment outcomes or the risk of nephrotoxicity. Loading dose and inhaled colistin use near the time of IV colistin therapy may be considered to maximize therapeutic effectiveness and minimize the risk of colistin-associated nephrotoxicity, respectively.

Highlights

With the development of the colistin target Css,avg-based dosing algorithm, colistin doses are mostly determined based on the desired target Css,avg upon the discretion of the clinician treating the patient[15,16]
Considering the narrow therapeutic window of colistin, it is pertinent for clinicians to use the most appropriate desired target Css,avg for optimal treatment outcomes[13]
Previous studies suggested conflicting evidence regarding the relationship of colistin dose or concentration with treatment outcomes[24,25,26,27,28,29,30,31,32,33]

Summary

Introduction

To achieve the colistin target of fAUC:MIC of 12 to 48 for an organism with an MIC of 1 mg/L, the fAUC:MIC of 12 to 48 correspond to the target average steady-state total plasma colistin concentrations (Css,avg) of 1 to 4 mg/L. This target Css,avg was not considered in the current dosages approved by the Food and Drug Administration (FDA) in the United States: 2.5 to 5 mg/kg daily in 2 to 4 divided doses for patients with normal renal function with dosage adjusted based on the renal function of each patient[14]. The objective of this study was to evaluate the effect of the desired target colistin Css,avg for dosing on the effectiveness and safety of IV colistin therapy in critically ill patients

Objectives

Methods

Results

Conclusion