Comparison of adverse events and hospital length of stay associated with various amphotericin B formulations: sequential conventional amphotericin b/lipid versus lipid-only therapy for the treatment of invasive fungal infections in hospitalized patients.
OBJECTIVE
Patients with invasive fungal infections are often treated initially with conventional amphotericin B deoxycholate (CAB), followed by a switch to lipid-based formulations of amphotericin B (LF-AMB). Our study examined adverse events and hospital length of stay (LOS) among adults who received LF-AMB exclusively or CAB followed by LF-AMB (CAB/LF-AMB).


METHODS
Data were extracted from the Cerner Health Facts database. The study included adults with evidence of infection by Aspergillus, Candida, or Cryptococcus in addition to either renal insufficiency, a clinical condition suggesting intolerance to CAB, or CAB exposure within 90 days of admission. Nephrotoxicity was defined as a serum creatinine (SCr) level exceeding a 100% increase from baseline and an absolute level above 1.2 mg/dL. We used a hierarchical mixed-effect logistic regression model with nephrotoxicity as the outcome for the multivariate analysis.


RESULTS
The study included 327 LF-AMB and 81 CAB/LF-AMB patients with similar demographics and baseline SCr values. The mean pre-to-post percentage increase in SCr levels was greater for CAB/LF-AMB (122.9%) compared with LF-AMB (62.2%) (P < 0.001). The multivariate-adjusted odds ratio of nephrotoxicity was 5.93, for a 95% confidence interval of 2.92 to 12.05 (P < 0.001) for CAB/LF-AMB compared with LF-AMB. Hypokalemia, hypomagnesemia, and infusion-related reactions were more frequent with CAB/LF-AMB. Compared with the LF-AMB group, the CAB/LF-AMB patients had a longer post-amphotericin B LOS (24.1 days vs. 15.7 days, respectively; P < 0.001), with a marginal effect of 4.5 days longer for those receiving CAB/LF-AMB (P = 0.016).


CONCLUSIONS
In this retrospective study, we noted a significantly longer post-amphotericin B LOS and a greater frequency of adverse events, including nephrotoxicity, for patients whose initial treatment was CAB and who were switched to LF-AMB, compared with patients who received LF-AMB only.
Rolin L. Wade is a Healthcare Executive at Cerner Research in Culver City, California. Paresh Chaudhari is a Health Economics and Outcomes Researcher at Astellas Pharma US in Northbrook, Illinois. Jaime L. Natoli is a Senior Consultant at Kaiser Permanente in Los Angeles, California, and at the time of this writing, she was an employee at Cerner Research. Robert J. Taylor is a Scientist at Cerner Research in Culver City. Brian H. Nathanson is Chief Executive Officer at OptiStatim LLC in Longmeadow, Massachusetts. David Horn is a Physician Consultant in Doylestown, Pennsylvania.
Rolin L
RL
Wade
Paresh
P
Chaudhari
Jaime L
JL
Natoli
Robert J
RJ
Taylor
Brian H
BH
Nathanson
David
D
Horn
adverse events; amphotericin B; hospital length of stay; invasive fungal infections; nephrotoxicity