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Impact of decreasing vancomycin exposure on acute kidney injury in stem cell transplant recipients

Published online by Cambridge University Press:  07 December 2021

Horace Rhodes Hambrick Open the ORCID record for Horace Rhodes Hambrick [Opens in a new window] ,
Kimberly F. Greco ,
Edie Weller ,
Lakshmi Ganapathi ,
Leslie E. Lehmann  and
Thomas J. Sandora Open the ORCID record for Thomas J. Sandora [Opens in a new window]
Horace Rhodes Hambrick*
Affiliation:
Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatric Nephrology, Cincinnati Children’s Hospital Medical Center, Cincinnati, Ohio
Kimberly F. Greco
Affiliation:
Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts
Edie Weller
Affiliation:
Biostatistics and Research Design Center, Institutional Centers for Clinical and Translational Research, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatrics, Harvard Medical School, Boston, Massachusetts
Lakshmi Ganapathi
Affiliation:
Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Division of Nephrology, Boston Children’s Hospital, Boston, Massachusetts Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts
Leslie E. Lehmann
Affiliation:
Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Pediatric Stem Cell Transplant, Dana-Farber Cancer Institute, Boston, Massachusetts
Thomas J. Sandora
Affiliation:
Department of Pediatrics, Boston Children’s Hospital, Boston, Massachusetts Department of Pediatrics, Harvard Medical School, Boston, Massachusetts Division of Infectious Diseases, Boston Children’s Hospital, Boston, Massachusetts
*
Author for correspondence: Horace Rhodes Hambrick, E-mail: [email protected]
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Abstract

Objective:

To evaluate the change in vancomycin days of therapy (DOT) and vancomycin-associated acute kidney injury (AKI) after an antimicrobial stewardship program (ASP) intervention to decrease vancomycin use in stable patients after hematopoietic stem cell transplantation (HSCT).

Design:

Retrospective cohort study and quasi-experimental interrupted time series analysis. Change in unit-level vancomycin DOT per 1,000 inpatient days after the intervention was assessed using segmented Poisson regression. Subject-specific risk of vancomycin-associated AKI was evaluated using a random intercept logistic regression model with mediation analysis.

Setting:

HSCT unit at a single quaternary-care pediatric hospital.

Participants:

Inpatients aged 3 months and older who underwent HSCT between January 1, 2015, and March 31, 2019 (27 months before and after the intervention) who received any dose of vancomycin.

Intervention:

An ASP intervention in April 2017 creating a new practice guideline to decrease prolonged (>72 hours) vancomycin courses for stable HSCT patients with febrile neutropenia.

Results:

Overall, 439 vancomycin exposures (234 before the intervention and 205 after the intervention) occurring across 300 transplants and 259 subjects were included. The mean vancomycin DOT was 307 per 1,000 inpatient days (95% confidence interval [CI], 272–342) and decreased after the intervention to 207 per 1,000 inpatient days (95% CI, 173–240). In multivariable analyses, the odds of AKI in the postintervention period were 37% lower than in the preintervention period (adjusted OR, 0.63; 95% CI, 0.42–0.95; P = .0268); 56% of the excess risk was mediated by vancomycin DOT.

Conclusions:

An ASP intervention successfully decreased vancomycin use after HSCT and resulted in a decrease in AKI. Reducing empiric antibiotic exposure for stable patients after HSCT can improve clinical outcomes.

Type
Original Article
Information
Infection Control & Hospital Epidemiology , Volume 43 , Issue 10 , October 2022 , pp. 1375 - 1381
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Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of The Society for Healthcare Epidemiology of America

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Footnotes

PREVIOUS PRESENTATION. This work was presented in a poster session at the May 2021 meeting of the Pediatric Academic Societies, held virtually.

References

Henig, I, Zuckerman, T. Hematopoietic stem cell transplantation—50 years of evolution and future perspectives. Rambam Maimonides Med J 2014;5:e0028.CrossRefGoogle ScholarPubMed
Crotta, A, Zhang, J, Keir, C. Survival after stem-cell transplant in pediatric and young-adult patients with relapsed and refractory B-cell acute lymphoblastic leukemia. Curr Med Res Opin 2018; 34: 435–440.CrossRefGoogle ScholarPubMed
Michael, M, Kuehnle, I, Goldstein, SL. Fluid overload and acute renal failure in pediatric stem cell transplant patients. Pediatr Nephrol 2004; 19: 91–95.CrossRefGoogle ScholarPubMed
Flores, FX, Brophy, PD, Symons, JM, et al. Continuous renal replacement therapy (CRRT) after stem cell transplantation: a report from the prospective pediatric CRRT Registry Group. Pediatr Nephrol 2008; 23: 625–630.Google ScholarPubMed
Patzer, L, Kentouche, K, Ringelmann, F, Misselwitz, J. Renal function following hematological stem cell transplantation in childhood. Pediatr Nephrol 2003; 18: 623–635.CrossRefGoogle ScholarPubMed
Kist-van Holthe, JE, Van Zwet, JML, Brand, R, Van Weel, MH, Vossen, JMJJ, Van der Heijden, AJ. Bone marrow transplantation in children: consequences for renal function shortly after and 1 year post-BMT. Bone Marrow Transpl 1998; 22: 559–564.CrossRefGoogle ScholarPubMed
Caliskan, Y, Besisik, SK, Sargin, D, Ecder, T. Early renal injury after myeloablative allogeneic and autologous hematopoietic cell transplantation. Bone Marrow Transpl 2006; 38: 141–147.CrossRefGoogle ScholarPubMed
Lopes, JA, Jorge, S, Silva, S, et al. Acute renal failure following myeloablative autologous and allogeneic hematopoietic cell transplantation. Bone Marrow Transpl 2006;38:707.Google ScholarPubMed
Raina, R, Herrera, N, Krishnappa, V, et al. Hematopoietic stem cell transplantation and acute kidney injury in children: a comprehensive review. Pediatr Transpl 2017; 21: 1–14. doi:10.1111/petr.12935 CrossRefGoogle ScholarPubMed
Kist-van Holthe, JE, Goedvolk, CA, Brand, R, et al. Prospective study of renal insufficiency after bone marrow transplantation. Pediatr Nephrol 2002; 17: 1032–1037.CrossRefGoogle ScholarPubMed
Ileri, T, Ertem, M, Ozcakar, ZB, et al. Prospective evaluation of acute and chronic renal function in children following matched related donor hematopoietic stem cell transplantation. Pediatr Transpl 2010; 14: 138–144.CrossRefGoogle ScholarPubMed
Krishnappa, V, Gupta, M, Manu, G, Kwatra, S, Owusu, O-T, Raina, R. Acute kidney injury in hematopoietic stem cell transplantation: a review. Int J Nephrol 2016;2016:5163789.CrossRefGoogle ScholarPubMed
Sorkine, P, Nagar, H, Weinbroumm, A, et al. Administration of amphotericin B in lipid emulsion decreases nephrotoxicity: results of a prospective, randomized, controlled study in critically ill patients. Crit Care Med 1996; 24: 1311–1315.CrossRefGoogle ScholarPubMed
Hazar, V, Gungor, O, Gur Guven, A, et al. Renal function after hematopoietic stem cell transplantation in children. Pediatr Blood Cancer 2009; 53: 197–202.CrossRefGoogle ScholarPubMed
Didsbury, MS, Mackie, FE, Kennedy, SE. A systematic review of acute kidney injury in pediatric allogeneic hematopoietic stem cell recipients. Pediatr Transpl 2015; 19: 460–470.CrossRefGoogle ScholarPubMed
Jeffres, MN. The whole price of vancomycin: toxicities, troughs, and time. Drugs 2017; 77: 1143–1154.CrossRefGoogle Scholar
Balcı, C, Uzun, Ö, Arıcı, M, Hayran, SA, Yüce, D, Ünal S. Nephrotoxicity of piperacillin/tazobactam combined with vancomycin: should it be a concern? Int J Antimicrob Agents 2018; 52: 180–184.CrossRefGoogle ScholarPubMed
Benoit, SW, Goldstein, SL, Dahale, DS, et al. Reduction in nephrotoxic antimicrobial exposure decreases associated acute kidney injury in pediatric hematopoietic stem cell transplant patients. Biol Blood Marrow Transplant 2019; 25: 1654–1658.CrossRefGoogle ScholarPubMed
Luther, MK, Timbrook, TT, Caffrey, AR, Dosa, D, Lodise, TP, Laplante, KL. Vancomycin plus piperacillin-tazobactam and acute kidney injury in adults: a systematic review and meta-analysis. Crit Care Med 2018; 46: 12–20.CrossRefGoogle ScholarPubMed
Downes, KJ, Cowden, C, Laskin, BL, et al. Association of acute kidney injury with concomitant vancomycin and piperacillin/tazobactam treatment among hospitalized children. JAMA Pediatr 2017;171:e173219.CrossRefGoogle ScholarPubMed
Belayev, LY, Palevsky, P. The link between AKI and CKD. Curr Opin Nephrol Hypertens 2015; 23: 149–154.CrossRefGoogle Scholar
Kanduri, SR, Cheungpasitporn, W, Thongprayoon, C, et al. Incidence and mortality of acute kidney injury in patients undergoing hematopoietic stem cell transplantation: a systematic review and meta-analysis. QJM An Int J Med 2020; 113: 621–632.CrossRefGoogle ScholarPubMed
Kellum, JA, Lameire, N, Aspelin, P, et al. Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl 2012; 2: 1–138.Google Scholar
Schetz, M, Dasta, J, Goldstein, S, Golper, T. Drug-induced acute kidney injury. Curr Opin Crit Care 2005; 11: 555–565.CrossRefGoogle ScholarPubMed
Goldstein, SL, Mottes, T, Simpson, K, et al. A sustained quality improvement program reduces nephrotoxic medication-associated acute kidney injury. Kidney Int 2016; 90: 212–222.CrossRefGoogle ScholarPubMed
Valeri, L, VanderWeele, TJ. Mediation analysis allowing for exposure-mediator interactions and causal interpretation: theoretical assumptions and implementation with SAS and SPSS macros. Psychol Methods 2013; 18: 137–150.CrossRefGoogle ScholarPubMed
Bunchman, TE, McBryde, KD, Mottes, TE, Gardner, JJ, Maxvold, NJ, Brophy, PD. Pediatric acute renal failure: outcome by modality and disease. Pediatr Nephrol 2001; 16: 1067–1071.CrossRefGoogle ScholarPubMed
Goldstein, SL, Dahale, D, Kirkendall, ES, et al. A prospective multicenter quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children. Kidney Int 2020; 97: 580–588.CrossRefGoogle Scholar
Clemmons, AB, Bech, CF, Pantin, J, Ahmad, I. Acute kidney injury in hematopoietic cell transplantation patients receiving vancomycin and piperacillin/tazobactam versus vancomycin and cefepime. Biol Blood Marrow Transpl 2017; 24: 820–826.CrossRefGoogle ScholarPubMed
Sinclair, EA, Yenokyan, G, McMunn, A, Fadrowski, JJ, Milstone, AM, Lee, CKK. Factors associated with acute kidney injury in children receiving vancomycin. Ann Pharmacother 2014; 48: 1555–1562.CrossRefGoogle ScholarPubMed
McKamy, S, Hernandez, E, Jahng, M, Moriwaki, T, Deveikis, A, Le, J. Incidence and risk factors influencing the development of vancomycin nephrotoxicity in children. J Pediatr 2011; 158: 422–426.CrossRefGoogle ScholarPubMed
Kullar, R, Davis, SL, Levine, DP, Rybak, MJ. Impact of vancomycin exposure on outcomes in patients with methicillin-resistant Staphylococcus aureus bacteremia: support for consensus guidelines suggested targets. Clin Infect Dis 2011; 52: 975–981.CrossRefGoogle ScholarPubMed
Bamgbola, O. Review of vancomycin-induced renal toxicity: an update. Ther Adv Endocrinol Metab 2016; 7: 136–147.CrossRefGoogle ScholarPubMed
Shen, WC, Chiang, YC, Chen, HY, et al. Nephrotoxicity of vancomycin in patients with methicillin-resistant Staphylococcus aureus bacteraemia. Nephrology 2011; 16: 697–703.CrossRefGoogle ScholarPubMed
Esiashvili, N, Chiang, K-Y, Hasselle, MD, Bryant, C, Riffenburgh, RH, Paulino, AC. Renal toxicity in children undergoing total body irradiation for bone marrow transplant. Radiother Oncol. 2009; 90: 242–246.CrossRefGoogle ScholarPubMed
Campbell, CA, Li, L, Kotwal, S, et al. Underdetection of acute kidney injury in hospitalised patients: a retrospective, multisite, longitudinal study. Intern Med J 2020; 50: 307–314.CrossRefGoogle Scholar
Laskin, BL, Goebel, J, Davies, SM, Jodele, S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011; 118: 1452–1462.CrossRefGoogle ScholarPubMed
Laskin, BL, Goebel, J, Davies, SM, et al. Early clinical indicators of transplant-associated thrombotic microangiopathy in pediatric neuroblastoma patients undergoing auto-SCT. Bone Marrow Transpl 2011; 46: 682–689.CrossRefGoogle ScholarPubMed
Filler, G, Lee, M. Educational review: measurement of GFR in special populations. Pediatr Nephrol 2018; 33: 2037–2046.Google ScholarPubMed
Laskin, BL, Nehus, E, Goebel, J, Furth, S, Davies, SM, Jodele, S. Estimated versus measured glomerular filtration rate in children before hematopoietic cell transplantation. Biol Blood Marrow Transpl 2014; 20: 2056–2061.CrossRefGoogle ScholarPubMed