Abstract
Population pharmacokinetic studies have suggested that high polymyxin B (PMB) doses (≥30,000 IU/kg/day) can improve bacterial kill in carbapenem-resistant Gram-negative bacteria (CR-GNB). We aim to describe the efficacy and nephrotoxicity of patients with CR-GNB infections prescribed high-dose PMB. A single-centre cohort study was conducted from 2013 to 2016 on septic patients with CR-GNB infection and prescribed high-dose PMB (~30,000 IU/kg/day) for ≥72 h. Study outcomes included 30-day mortality and acute kidney injury (AKI) development. Factors associated with AKI were identified using multivariable regression. Forty-three patients with 58 CR-GNB received high-dose PMB; 57/58 (98.3%) CR-GNB were susceptible to PMB. The median daily dose and duration of high-dose PMB were 32,051 IU/kg/day (IQR, 29,340–34,884 IU/kg/day) and 14 days (IQR, 7–28 days), respectively. Thirty-day mortality was observed in 7 (16.3%) patients. AKI was observed in 25 (58.1%) patients with a median onset of 8 days (IQR, 6–13 days). Higher daily PMB dose (aOR,1.01; 95% CI, 1.00–1.02) and higher number of concurrent nephrotoxins (aOR, 2.14; 95% CI; 1.03–4.45) were independently associated with AKI. We observed that a sizable proportion developed AKI in CR-GNB patients described high-dose PMB; hence, the potential benefits must be weighed against increased AKI risk. Concurrent nephrotoxins should be avoided to reduce nephrotoxicity.
Highlights
In the last decade, the global spread of carbapenem-resistant Gram negative bacteria (CR-GNB)has led to the reintroduction of polymyxin B [1,2]
All patients admitted from July 2013 to December 2016 with microbiologic evidence of carbapenem-resistant Gram-negative bacteria (CR-GNB) infection and sepsis due to the CR-GNB infection and prescribed high-dose polymyxin B for ≥72 h for the CR-GNB infection were included [11]
Unlike colistin, which is administered as a prodrug, polymyxin B is administered in its active antibacterial form, which results in a rapid and reliable attainment of the plasma concentration of the active constituent upon administration [3,23,24]
Summary
The global spread of carbapenem-resistant Gram negative bacteria (CR-GNB)has led to the reintroduction of polymyxin B [1,2]. The rekindled reliance on this once forsaken antibiotic has resulted in several questions regarding the clinical use of polymyxin B (e.g., doses in specific populations, toxicity profile) [1,3]. Antibiotics 2020, 9, 451 pharmacodynamic properties are scarce and there is a paucity of information regarding its clinical use [1,3,4]. There remains a lack of consensus on the most appropriate dosing regimen for polymyxin. A landmark population pharmacokinetics study has suggested that for organisms with polymyxin B MIC of ≤2 mg/L, higher polymyxin B doses may be necessary to achieve a ratio of the area under the concentration–time curve of the unbound antibiotic to the MIC (f AUC/MIC) of
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