QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis
© 2023 The Authors..
Rationale & Objective: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin.
Study Design: Retrospective observational cohort study using a new-user study design.
Setting & Population: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017).
Exposure: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses.
Outcomes: Sudden cardiac death (14 days).
Analytical Approach: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs.
Results: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results.
Limitations: Residual confounding.
Conclusions: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics.
| Errataetall: |
CommentIn: Kidney Med. 2023 Apr 11;5(5):100638. - PMID 37168388 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:5 |
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| Enthalten in: |
Kidney medicine - 5(2023), 5 vom: 21. Mai, Seite 100618 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Pun, Patrick H [VerfasserIn] |
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| Links: |
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| Themen: |
Azithromycin |
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| Anmerkungen: |
Date Revised 11.05.2023 published: Electronic-eCollection CommentIn: Kidney Med. 2023 Apr 11;5(5):100638. - PMID 37168388 Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1016/j.xkme.2023.100618 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM356167372 |
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| 100 | 1 | |a Pun, Patrick H |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a QT-Prolonging Antibiotics, Serum-to-Dialysate Potassium Gradient, and Risk of Sudden Cardiac Death Among Patients Receiving Maintenance Hemodialysis |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Revised 11.05.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a CommentIn: Kidney Med. 2023 Apr 11;5(5):100638. - PMID 37168388 | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023 The Authors. | ||
| 520 | |a Rationale & Objective: Treatment with certain QT interval-prolonging antibiotics is associated with a higher risk of sudden cardiac death among individuals with hemodialysis-dependent kidney failure. Concurrent exposure to large serum-to-dialysate potassium gradients, which promote large potassium shifts, may augment the proarrhythmic effects of these medications. The primary objective of this study was to examine whether the serum-to-dialysate gradient modifies the cardiac safety of azithromycin, and separately, levofloxacin/moxifloxacin | ||
| 520 | |a Study Design: Retrospective observational cohort study using a new-user study design | ||
| 520 | |a Setting & Population: Adult in-center hemodialysis patients with Medicare coverage in the US Renal Data System (2007-2017) | ||
| 520 | |a Exposure: Initiation of azithromycin (or levofloxacin/moxifloxacin) as compared to amoxicillin-based antibiotics (exposure). Serum-to-dialysate potassium gradient (effect modifier). Individual patients could contribute multiple study antibiotic treatment episodes to the analyses | ||
| 520 | |a Outcomes: Sudden cardiac death (14 days) | ||
| 520 | |a Analytical Approach: Inverse probability of treatment-weighted survival models to estimate HRs and robust 95% CIs | ||
| 520 | |a Results: The azithromycin versus amoxicillin-based antibiotic cohort included 89,379 unique patients with 113,516 azithromycin and 103,493 amoxicillin-based treatment episodes. Azithromycin versus amoxicillin-based antibiotic treatment was associated with a higher risk of sudden cardiac death overall, HR, 1.68; 95% CI, 1.31-2.16. The risk was numerically higher when the baseline serum-to-dialysate potassium gradient was ≥3 mEq/L compared with <3 mEq/L (HR, 2.22; 95% CI, 1.46-3.40 vs HR, 1.43; 95% CI. 1.04-1.96, P interaction = 0.07). Analogous analyses in a respiratory fluoroquinolone (levofloxacin/moxifloxacin) versus amoxicillin-based antibiotic cohort with 79,449 unique patients and 65,959 respiratory fluoroquinolone and 103,776 amoxicillin-based treatment episodes yielded similar results | ||
| 520 | |a Limitations: Residual confounding | ||
| 520 | |a Conclusions: Although treatment with azithromycin and, separately, respiratory fluoroquinolones were each associated with a heightened risk of sudden cardiac death, this risk was augmented in the setting of larger serum-to-dialysate potassium gradients. Minimizing the potassium gradient may be an approach to reduce the cardiac risk of these antibiotics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Azithromycin | |
| 650 | 4 | |a USRDS | |
| 650 | 4 | |a dialysate potassium | |
| 650 | 4 | |a fluoroquinolones | |
| 650 | 4 | |a hemodialysis | |
| 650 | 4 | |a sudden cardiac death | |
| 700 | 1 | |a Assimon, Magdalene M |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Lily |e verfasserin |4 aut | |
| 700 | 1 | |a Al-Khatib, Sana M |e verfasserin |4 aut | |
| 700 | 1 | |a Brookhart, M Alan |e verfasserin |4 aut | |
| 700 | 1 | |a Weber, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Winkelmayer, Wolfgang C |e verfasserin |4 aut | |
| 700 | 1 | |a Flythe, Jennifer E |e verfasserin |4 aut | |
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