Risk of Nephrotoxicity Associated With Nonrenally Adjusted Intravenous Polymyxin B Compared to Traditional Dosing

Abstract

Background: Polymyxin B’s package insert recommends renal adjustment. Contemporary studies suggest it does not require renal adjustment. Objective: To determine whether time to acute kidney injury (AKI) differs between renally adjusted and nonadjusted intravenous (IV) polymyxin B. Methods: This retrospective chart review compared time to AKI after renally adjusted and nonadjusted IV polymyxin B administration. It included patients who were 18 years or older, received IV polymyxin B, and had creatinine clearance below 80 mL/min, and excluded ones who had AKI, received renal replacement therapy, or were pregnant. Results: Fifty-four patients were included. There was not any statistical association between dosing type and time to AKI ( P = .13). Incidence of nephrotoxicity, mortality, and length of stay (LOS) were higher in the renally adjusted arm (21.7% vs 6.5%, 17.4% vs 6.5%, and 16 vs 14 days, respectively). Four patients received concomitant ascorbic acid; not one developed AKI. Conclusion: A significant association between IV polymyxin B dosing type and time to AKI was not found. Adverse events were higher in the renally adjusted arm. This suggests that nonadjusted IV polymyxin B may be preferred in patients with renal impairment. Ascorbic acid may mitigate IV polymyxin B's nephrotoxic potential. Further studies are needed to corroborate these findings.

Risk of Polymyxin B-induced Acute Kidney Injury in Non-adjusted Dose Versus Adjusted Dose based on Renal Function: a retrospective cohort study

“…The pathogenesis of AKI in severe infection or sepsis is highly related to renal hypoperfusion derived from the toxic effects of inflammation and impaired microcirculation[34]. A single-center, retrospective study with 54 patients was implemented by Maniara et al also obtained a similar result that subtherapeutic doses from renal adjustment could lead to unresolved infections and a higher incidence of AKI[35]. In consequence, renal dosing adjustment of PMB is unnecessary for patients with kidney function impairment.…”

“…Peyko et al found that patients who received renally adjusted PMB doses owned higher LOS and mortality due to PMB underdose against infection[36]. Research from Maniara et al showed that renal dose adjustment of PMB did not affect microbiological cure, clinical cure, or 30-day mortality[35]. In this aspect, dosing without renal adjustment is a proper PMB dosing strategy to increase the probability of meeting the therapeutic target and get a better curative rate ultimately.…”

Clinical outcomes and safety of polymyxin B in the treatment of carbapenem-resistant Gram-negative bacterial infections: a real-world multicenter study

“…The organisms most commonly identified in CR-GNB infections are Klebsiella pneumoniae , Acinetobacter baumannii , and Pseudomonas aeruginosa [ 2 – 4 ]. These bacteria can lead to bloodstream, respiratory tract, skin and soft tissue, urinary tract, intra-abdominal, and surgical infections [ 3 , 5 – 7 ]. They are responsible for nosocomial infections, particularly among critically ill patients hospitalized in intensive care units (ICUs) [ 8 ].…”

Clinical Outcomes and Safety of Polymyxin B in the Treatment of Carbapenem-resistant Gram-negative Bacterial Infections: a Real-world Multicenter Study

“…The organisms most commonly identi ed in CR-GNB infections are Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa [2][3][4]. These bacteria can lead to bloodstream, respiratory tract, skin and soft tissue, urinary tract, intra-abdominal, and surgical infections [3,[5][6][7]. They are responsible for nosocomial infections, particularly among critically ill patients hospitalized in intensive care units (ICUs) [8].…”