Nephrotoxicity in Patients with or without Cystic Fibrosis Treated with Polymyxin B Compared to Colistin.
Nephrotoxicity is the primary adverse effect of the polymyxins. The relative rates of toxicity of polymyxin B and colistin have not been fully elucidated, especially in patients with cystic fibrosis (CF). A retrospective cohort study of adults treated with polymyxin B or colistin for at least 48 h was conducted. The primary endpoint was the incidence of kidney injury assessed by RIFLE (i.e.,risk,injury,failure,loss,end-stage renal disease) criteria. Risk factors for kidney injury were evaluated using multivariate Cox regression. A total of 414 patients were evaluated, 220 of whom had CF. In patients without CF, there was no difference in kidney injury with polymyxin B and colistin (42.9% versus 50.3%,P= 0.46). Loop diuretic exposure was a risk factor for kidney injury (adjusted hazard ratio [aHR], 1.82; 95% confidence interval [CI], 1.16 to 2.83) in this population. In patients with CF, polymyxin B and colistin were associated with similar rates of kidney injury (34.5% versus 29.8%,P= 0.77). Diabetes (aHR, 2.68; 95% CI, 1.01 to 7.11), loop diuretics (aHR, 3.02; 95% CI, 1.36 to 6.73), and progressive care unit admission (aHR, 8.21; 95% CI, 2.55 to 26.46) were risk factors for kidney injury, while higher baseline serum creatinine levels (per 1 mg/dl) were protective (aHR, 0.08; 95% CI, 0.01 to 0.48). Total unadjusted kidney injury in polymyxin-treated patients was less frequent in those who had CF (30.5% versus 48.5%,P< 0.001). Polymyxin B and colistin are associated with a high incidence of kidney injury; cystic fibrosis may be protective against polymyxin nephrotoxicity, but further investigation is needed to confirm this conjecture.
Department of Pharmacy Services, UK HealthCare, Lexington, Kentucky, USA.
Ryan L
RL
Crass
Department of Pharmacy Services, UK HealthCare, Lexington, Kentucky, USA.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.
W Cliff
WC
Rutter
Department of Pharmacy Services, UK HealthCare, Lexington, Kentucky, USA.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.
Donna R
DR
Burgess
Department of Pharmacy Services, UK HealthCare, Lexington, Kentucky, USA.|Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA.
Craig A
CA
Martin
Department of Pharmacy Practice and Science, University of Kentucky College of Pharmacy, Lexington, Kentucky, USA david.burgess@uky.edu.
David S
DS
Burgess
D058186:Acute Kidney Injury / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000473:pathology; D000328:Adult; D000368:Aged; D000900:Anti-Bacterial Agents / Q000009:adverse effects* / Q000493:pharmacokinetics; D001424:Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D003091:Colistin / Q000009:adverse effects* / Q000493:pharmacokinetics; D003404:Creatinine / Q000097:blood; D003550:Cystic Fibrosis / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology; D003920:Diabetes Mellitus / Q000503:physiopathology; D005260:Female; D006760:Hospitalization; D006801:Humans; D007362:Intensive Care Units; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000009:adverse effects* / Q000493:pharmacokinetics; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000009:adverse effects
D000900:Anti-Bacterial Agents; D049994:Sodium Potassium Chloride Symporter Inhibitors; D003404:Creatinine; D011112:Polymyxin B; D003091:Colistin
clinical therapeutics; multidrug resistance; pharmacokinetics; pharmacology; toxicity