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.

Ceftolozane/tazobactam is an intravenous beta-lactam/beta-lactamase inhibitor that utilizes a novel oxyimino-cephalosporin with a traditional beta-lactamase inhibitor. It is approved by the Food and Drug Administration to treat complicated intra-abdominal infections in combination with metronidazole, complicated urinary tract infections, and, most recently, hospital-acquired bacterial and ventilator-associated bacterial pneumonias. It is commonly utilized to treat infections caused by multidrug-resistant Pseudomonas aeruginosa. This case report delineates the first published case of ceftolozane/tazobactam-induced leukocytosis (up to 36.9 × 10 9 cells/L) and clinical failure when utilized in a high-dose regimen for a patient being treated for ventilatorassociated pneumonia secondary to carbapenem-resistant P. aeruginosa. The reaction occurred during initial challenge, resolved after discontinuation, and recurred during re-challenge. In patients who are appropriately being treated with ceftolozane/ tazobactam for susceptible infections, consider a drug-induced reaction as a potential cause of rising leukocytosis; this should be differentiated from clinical failure if the patient is clinically stable.

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BackgroundPrior data states that polymyxin B is renally cleared and thus required renal adjustments, however newer data suggests that polymyxin B undergoes non-renal clearance. With more aggressive dosing, potential for increased nephrotoxicity is of concern. This study aims to determine whether time to acute kidney injury (AKI) differs between renally adjusted and non-adjusted doses of intravenous (IV) polymyxin B. Secondary objectives aim to evaluate incidence of AKI, length of stay (LOS), adverse reactions, and potential role of ascorbic acid in decreasing nephrotoxicity.MethodsThis retrospective chart review compared time to AKI in patients receiving renally adjusted and non-adjusted IV polymyxin B between Jan 2012 and Nov 2016. This study included patients who are at least 18 years old, received IV polymyxin B, and have creatinine clearance below 80 mL/minute. Patients were excluded if they had AKI (RIFLE criteria), received renal replacement therapy, or are pregnant prior to receipt of IV polymyxin B. Fine and Gray’s model for competing risks was used to predict the cumulative incidence function of AKI. Descriptive statistics, two-sample t-test, and Chi-square test were used as appropriate.ResultsOf the 132 patients screened, 54 met inclusion criteria (23 in the renally adjusted vs. 31 in the non-adjusted group). There was no statistical association between dosing type and time to AKI (P = 0.13). Incidence of nephrotoxicity was higher in the renally adjusted vs. non-adjusted groups (21.7% vs. 6.5% respectively). Mortality was higher in the renally adjusted vs. non-adjusted groups (17.4% vs. 6.5% respectively). LOS was greater in the renally adjusted vs. non-adjusted groups (16 vs. 14 days respectively, P = 0.26). All patients in the study received concomitant nephrotoxic agents (e.g., vancomycin, aminoglycosides). Ascorbic acid use was infrequent but, in the 4 patients who did receive it, none developed AKI. No difference in neurotoxicity, respiratory arrest, Clostridium difficile infections was seen.ConclusionNo significant association between IV polymyxin B dosing type and time to AKI was found. Incidence of AKI, LOS, and mortality was higher in the renally adjusted group compared with the non-adjusted group. Ascorbic acid may mitigate the nephrotoxic potential of IV polymyxin B, but further studies are needed.Disclosures All authors: No reported disclosures.