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. 2016 Dec 15;63(12):1605-1612.
doi: 10.1093/cid/ciw684. Epub 2016 Oct 6.

The Effectiveness and Safety of High-Dose Colistin: Prospective Cohort Study

Yael Dishon Benattar  1   2 , Muna Omar  3   4 , Oren Zusman  3   5 , Dafna Yahav  3   6 , Yael Zak-Doron  1   7 , Sergey Altunin  7 , Michal Elbaz  5 , Vered Daitch  5 , Michal Granot  2 , Leonard Leibovici  3   5 , Mical Paul  1   7
Affiliations

The Effectiveness and Safety of High-Dose Colistin: Prospective Cohort Study

Yael Dishon Benattar et al. Clin Infect Dis. .

Abstract

Background: Optimizing colistin dosing should translate to improved patient outcomes.

Methods: We used data from 2 prospective cohort studies performed between 2006 and 2009 and between 2012 and 2015. In the latter period, a new policy of high-dose colistin (9 million international units [MIU] loading dose followed by 9 MIU daily for normal renal function) was introduced in 2 participating hospitals. We included adult inpatients with invasive infections caused by carbapenem-resistant gram-negative bacteria treated with colistin. Our primary exposure variable was colistin dose, dichotomized to high-dose vs other regimens. The primary outcome was 28-day mortality. We generated a propensity score for high-dose colistin and conducted propensity-adjusted multivariable and matched-cohort analyses for mortality.

Results: Of 529 consecutive patients fulfilling inclusion criteria, 144 were treated with high-dose colistin and 385 with lower-dose colistin regimens. The median daily dose in the high-dose group was 9 MIU (interquartile range [IQR], 9-9) vs 4 MIU (IQR, 3-6) with other regimens. There were 50 of 144 (34.7%) deaths with high-dose colistin vs 165 of 385 (42.9%) with low-dose colistin (P = .1). The propensity-adjusted odds ratio (OR) for mortality was 1.07 (95% confidence interval [CI], .63-1.83) for high-dose colistin. Similar results were obtained when using the study period as the exposure variable, in the subgroup of bacteremic patients (n = 207) and in the propensity-matched cohort (OR, 1.11 [95% CI, .67-1.82]). Nephrotoxicity (RIFLE injury or higher; OR, 2.12 [95% CI, 1.29-3.48]; n = 396) and seizures were significantly more common with high-dose colistin.

Conclusions: In a large cohort, we found no association between high colistin dosing and all-cause mortality. High dosing was associated with more nephrotoxicity.

Keywords: Acinetobacter; Klebsiella; hospital-acquired infection; multidrug resistant gram-negative bacteria; polymyxin.

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Comment in

  • Editorial Commentary: Colistin Dosing: Does the Fun Ever Start?
    Pogue JM, Ortwine JK, Kaye KS. Pogue JM, et al. Clin Infect Dis. 2016 Dec 15;63(12):1613-1614. doi: 10.1093/cid/ciw685. Epub 2016 Oct 6. Clin Infect Dis. 2016. PMID: 27794022 No abstract available.
  • Reply to Zavascki and Nation.
    Paul M, Yahav D, Dishon Benattar Y, Leibovici L. Paul M, et al. Clin Infect Dis. 2017 Mar 1;64(5):696. doi: 10.1093/cid/ciw819. Clin Infect Dis. 2017. PMID: 27986667 No abstract available.