Outcomes Following Macrolide Use in Kidney Transplant Recipients
Background: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat a...
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Format: | Article |
Language: | English |
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SAGE Publishing
2019-02-01
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Series: | Canadian Journal of Kidney Health and Disease |
Online Access: | https://doi.org/10.1177/2054358119830706 |
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doaj-82e76dc0f4ac4f43bce3f80cd8476ef9 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Rachel Jeong Robert R. Quinn Krista L. Lentine Anita Lloyd Pietro Ravani Brenda Hemmelgarn Branko Braam Amit X. Garg Kevin Wen Anita Wong-Chan Sita Gourishankar Ngan N. Lam |
spellingShingle |
Rachel Jeong Robert R. Quinn Krista L. Lentine Anita Lloyd Pietro Ravani Brenda Hemmelgarn Branko Braam Amit X. Garg Kevin Wen Anita Wong-Chan Sita Gourishankar Ngan N. Lam Outcomes Following Macrolide Use in Kidney Transplant Recipients Canadian Journal of Kidney Health and Disease |
author_facet |
Rachel Jeong Robert R. Quinn Krista L. Lentine Anita Lloyd Pietro Ravani Brenda Hemmelgarn Branko Braam Amit X. Garg Kevin Wen Anita Wong-Chan Sita Gourishankar Ngan N. Lam |
author_sort |
Rachel Jeong |
title |
Outcomes Following Macrolide Use in Kidney Transplant Recipients |
title_short |
Outcomes Following Macrolide Use in Kidney Transplant Recipients |
title_full |
Outcomes Following Macrolide Use in Kidney Transplant Recipients |
title_fullStr |
Outcomes Following Macrolide Use in Kidney Transplant Recipients |
title_full_unstemmed |
Outcomes Following Macrolide Use in Kidney Transplant Recipients |
title_sort |
outcomes following macrolide use in kidney transplant recipients |
publisher |
SAGE Publishing |
series |
Canadian Journal of Kidney Health and Disease |
issn |
2054-3581 |
publishDate |
2019-02-01 |
description |
Background: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (−5.4 vs −1.9 mL/min/1.73 m 2 , P < .05). Limitations: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted. |
url |
https://doi.org/10.1177/2054358119830706 |
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doaj-82e76dc0f4ac4f43bce3f80cd8476ef92020-11-25T03:15:28ZengSAGE PublishingCanadian Journal of Kidney Health and Disease2054-35812019-02-01610.1177/2054358119830706Outcomes Following Macrolide Use in Kidney Transplant RecipientsRachel Jeong0Robert R. Quinn1Krista L. Lentine2Anita Lloyd3Pietro Ravani4Brenda Hemmelgarn5Branko Braam6Amit X. Garg7Kevin Wen8Anita Wong-Chan9Sita Gourishankar10Ngan N. Lam11Department of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartments of Community Health Sciences and Medicine, University of Calgary, Calgary, AB, CanadaCenter for Abdominal Transplantation, Saint Louis University School of Medicine, St. Louis, MO, USADepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Calgary, Calgary, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Calgary, Calgary, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartment of Medicine, Division of Nephrology, Western University, London, ON, CanadaDepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaDepartment of Medicine, Division of Nephrology, University of Alberta, Edmonton, AB, CanadaBackground: Calcineurin inhibitors (CNI; cyclosporine, tacrolimus) are critical for kidney transplant immunosuppression, but have multiple potential drug interactions, such as with macrolide antibiotics. Macrolide antibiotics (clarithromycin, erythromycin, and azithromycin) are often used to treat atypical infections. Clarithromycin and erythromycin inhibit CNI metabolism and increase the risk of CNI nephrotoxicity, while azithromycin does not. Objective: To determine the frequency of CNI-macrolide co-prescriptions, the proportion who receive post-prescription monitoring, and the risk of adverse drug events in kidney transplant recipients. Design: Retrospective cohort study. Setting: We used linked health care databases in Alberta, Canada. Patients: We included 293 adult kidney transplant recipients from 2008-2015 who were co-prescribed a CNI and macrolide. Measurements: The primary outcome was a composite of all-cause hospitalization, acute kidney injury (creatinine increase ≥0.3 mg/dL or 1.5 times baseline), or death within 30 days of the macrolide prescription. Methods: We identified CNI-macrolide co-prescriptions and compared outcomes in those who received clarithromycin/erythromycin versus azithromycin. We used a linear mixed-effects model to examine the mean change in serum creatinine and estimated glomerular filtration rate (eGFR). Results: Of the 293 recipients who were co-prescribed a CNI and a macrolide, 38% (n = 112) were prescribed clarithromycin/erythromycin while 62% (n = 181) were prescribed azithromycin. Compared with azithromycin users, clarithromycin/erythromycin users were less likely to have outpatient serum creatinine monitoring post-prescription (56% vs 69%, P = .03). There was no significant difference in the primary outcome between the 2 groups (17% vs 11%, P = .11); however, the risk of all-cause hospitalization was higher in the clarithromycin/erythromycin group (10% vs 3%, P = .02). The mean decrement in eGFR was significantly greater in the clarithromycin/erythromycin versus azithromycin group (−5.4 vs −1.9 mL/min/1.73 m 2 , P < .05). Limitations: We did not have CNI levels to correlate with the timing of CNI-macrolide co-prescriptions. We also did not have information regarding the indications for macrolide prescriptions. Conclusion: Clarithromycin and erythromycin were frequently co-prescribed in kidney transplant recipients on CNIs despite known drug interactions. Clarithromycin/erythromycin use was associated with a higher risk of hospitalization compared with azithromycin users. Safer prescribing practices in kidney transplant recipients are warranted.https://doi.org/10.1177/2054358119830706 |