Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia

Retrospective Analysis of the IMPACT-HAP Database

Ennie L. Cano, Nadia Z. Haque, Verna L. Welch, Cynthia M. Cely, Paula Peyrani, Ernesto G. Scerpella, Kimbal D. Ford, Marcus J. Zervos, Julio A. Ramirez, Daniel H Kett

Research output: Contribution to journalArticle

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Abstract

Background: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. Objective: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. Methods: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. Results: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; . P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; . P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; . P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (. P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, . P = 0.0003). Conclusions: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

Original languageEnglish
Pages (from-to)149-157
Number of pages9
JournalClinical Therapeutics
Volume34
Issue number1
DOIs
StatePublished - Jan 1 2012

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Vancomycin
Intensive Care Units
Pneumonia
Databases
Incidence
Odds Ratio
Therapeutics
Anti-Bacterial Agents
APACHE
Kaplan-Meier Estimate
Aminoglycosides
Mechanical Ventilators
Multicenter Studies
Observational Studies
Creatinine
Multivariate Analysis
Logistic Models
Regression Analysis
Guidelines
Delivery of Health Care

Keywords

  • Intensive care
  • Nephrotoxicity
  • Nosocomial pneumonia
  • Vancomycin

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

Cite this

Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia : Retrospective Analysis of the IMPACT-HAP Database. / Cano, Ennie L.; Haque, Nadia Z.; Welch, Verna L.; Cely, Cynthia M.; Peyrani, Paula; Scerpella, Ernesto G.; Ford, Kimbal D.; Zervos, Marcus J.; Ramirez, Julio A.; Kett, Daniel H.

In: Clinical Therapeutics, Vol. 34, No. 1, 01.01.2012, p. 149-157.

Research output: Contribution to journalArticle

Cano, Ennie L. ; Haque, Nadia Z. ; Welch, Verna L. ; Cely, Cynthia M. ; Peyrani, Paula ; Scerpella, Ernesto G. ; Ford, Kimbal D. ; Zervos, Marcus J. ; Ramirez, Julio A. ; Kett, Daniel H. / Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia : Retrospective Analysis of the IMPACT-HAP Database. In: Clinical Therapeutics. 2012 ; Vol. 34, No. 1. pp. 149-157.
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title = "Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia: Retrospective Analysis of the IMPACT-HAP Database",
abstract = "Background: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. Objective: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. Methods: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50{\%} above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. Results: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63{\%} were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4{\%}) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95{\%} CI, 1.9-13.9]; . P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95{\%} CI, 1.09-6.54]; . P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95{\%} CI, 1.02-1.23]; . P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7{\%} at a trough <10 mg/L to 34{\%} at >20 mg/L (. P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, . P = 0.0003). Conclusions: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.",
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author = "Cano, {Ennie L.} and Haque, {Nadia Z.} and Welch, {Verna L.} and Cely, {Cynthia M.} and Paula Peyrani and Scerpella, {Ernesto G.} and Ford, {Kimbal D.} and Zervos, {Marcus J.} and Ramirez, {Julio A.} and Kett, {Daniel H}",
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T1 - Incidence of Nephrotoxicity and Association With Vancomycin Use in Intensive Care Unit Patients With Pneumonia

T2 - Retrospective Analysis of the IMPACT-HAP Database

AU - Cano, Ennie L.

AU - Haque, Nadia Z.

AU - Welch, Verna L.

AU - Cely, Cynthia M.

AU - Peyrani, Paula

AU - Scerpella, Ernesto G.

AU - Ford, Kimbal D.

AU - Zervos, Marcus J.

AU - Ramirez, Julio A.

AU - Kett, Daniel H

PY - 2012/1/1

Y1 - 2012/1/1

N2 - Background: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. Objective: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. Methods: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. Results: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; . P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; . P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; . P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (. P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, . P = 0.0003). Conclusions: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

AB - Background: The 2005 guidelines from the American Thoracic Society and the Infectious Diseases Society of America recommend vancomycin trough levels of 15 to 20 mg/L for the therapy of hospital-acquired (HAP), ventilator-associated (VAP), and health care-associated (HCAP) pneumonia. Objective: The goal of this article was to report the incidence of nephrotoxicity and associated risk factors in intensive care unit patients who received vancomycin for the treatment of HAP, VAP, and HCAP. Methods: This was a retrospective analysis of data from a multicenter, observational study of pneumonia patients. Antibiotic-associated nephrotoxicity was defined as either an increase in serum creatinine ≥0.5 mg/dL or 50% above baseline, from initiation of vancomycin to 72 hours after completion of therapy. Univariate and multivariate logistic regression analyses were performed to identify risk factors for development of renal dysfunction. Results: Of the 449 patients in the database, 240 received at least one dose of vancomycin and 188 had sufficient data for analysis. In these 188 patients, 63% were male. Mean (SD) age was 58.5 (17.2) years, and the mean Acute Physiology and Chronic Health Evaluation II score was 19.4 (6.4). Nephrotoxicity occurred in 29 of 188 (15.4%) vancomycin-treated patients. In multivariate analysis, initial vancomycin trough levels ≥15 mg/L (odds ratio [OR], 5.2 [95% CI, 1.9-13.9]; . P = 0.001), concomitant aminoglycoside use (OR, 2.67 [95% CI, 1.09-6.54]; . P = 0.03), and duration of vancomycin therapy (OR for each additional treatment day, 1.12 [95% CI, 1.02-1.23]; . P = 0.02) were independently associated with nephrotoxicity. The incidence of nephrotoxicity increased as a function of the initial vancomycin trough level, rising from 7% at a trough <10 mg/L to 34% at >20 mg/L (. P = 0.001). The mean time to nephrotoxicity decreased from 8.8 days at vancomycin trough levels <15 mg/L to 7.4 days at >20 mg/L (Kaplan-Meier analysis, . P = 0.0003). Conclusions: Nephrotoxicity may be common among intensive care unit patients with pneumonia treated with broad-spectrum antibiotic therapy that includes vancomycin. The finding that an initial vancomycin trough level ≥15 mg/L may be an independent risk factor for nephrotoxicity highlights the need for additional studies to assess current recommendations for vancomycin dosing for ICU patients with pneumonia.

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KW - Nephrotoxicity

KW - Nosocomial pneumonia

KW - Vancomycin

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