Polymyxin B vs. colistin: the comparison of neurotoxic and nephrotoxic effects of the two polymyxins

Abstract

Background: The study aimed to compare polymyxin B with colistimethate sodium (CMS) regarding neurotoxicity, nephrotoxicity and 30-day mortality in patients with MDR Gram-negatives.

Methods: All adult patients who received polymyxin B or CMS for at least 24 h for the treatment of MDR microorganisms were evaluated retrospectively.

Results: Among 413 initially screened patients, 147 patients who were conscious and able to express their symptoms were included in the neurotoxicity analysis. 13 of 77 patients with polymyxin B and 1 of 70 with CMS had neurotoxic adverse events, mainly paresthesias. All events were reversible after drug discontinuation. Among 290 patients included in nephrotoxicity analysis, the incidence of acute kidney injury (AKI) was 44.7% and 40.0% for polymyxin B and CMS, respectively (p = 0.425). AKI occurred two days earlier with colistin than polymyxin B without statistical significance (median (IQR): 5 (3-11) vs. 7 (3-12), respectively, p = 0.701). Polymyxin therapy was withdrawn in 41.1% of patients after AKI occurred and CMS was more frequently withdrawn than polymyxin B (p = 0.025). AKI was reversible in 91.6% of patients with CMS and 79% with polymyxin B after the drug withdrawal. Older age, higher baseline serum creatinine and the use of at least two nephrotoxic drugs were independent factors associated with AKI (OR 1.05, p < 0.001; OR 2.99, p = 0.022 and OR 2.45, p = 0.006, respectively). Septic shock, mechanical ventilation, presence of a central venous catheter and Charlson comorbidity index (OR 2.13, p = 0.004; OR 3.37, p < 0.001; OR 2.47, p = 0.004 and OR 1.21, p p < 0.001, respectively) were the independent predictors of mortality. The type of polymyxin was not related to mortality.

Conclusions: Neurotoxicity is a relatively common adverse event that leads to drug withdrawal during polymyxins, particularly polymyxin B. Nephrotoxicity is very common during polymyxin therapy and the two polymyxins display similar nephrotoxic events with high reversibility rates after drug withdrawal. Close monitoring of AKI is crucial during polymyxin therapy, particularly, for elderly patients, patients who have high baseline creatinine, and using other nephrotoxic drugs.

Keywords: Colistin; Mortality; Nephrotoxicity; Neurotoxicity; Polymyxin B.

Fig. 1

Flowchart of the study

Fig. 2

Parameters related to nephrotoxicity

Fig. 3

Comparison of the onset of nephrotoxicity (Log-rank test, p = 0.323)

Fig. 4

The details of patients with nephrotoxicity reversal