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Impact of piperacillin/tazobactam on nephrotoxicity in patients with Gram-negative bacteraemia
Authors:Ronald G. Hall  Eunice Yoo  Andrew Faust  Terri Smith  Edward Goodman  Eric M. Mortensen  Jaffar Raza  Farbod Dehmami  Carlos A. Alvarez
Affiliation:1. Texas Tech University Health Sciences Center, Department of Pharmacy Practice, 5920 Forest Park Road, Suite 400, Dallas, TX 75235, USA;2. VA North Texas Health Care System, 4500 S. Lancaster Road, Dallas, TX 75216, USA;3. University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390, USA;4. Dose Optimization and Outcomes Research (DOOR) Program, 5920 Forest Park Road, Suite 400, Dallas, TX 75235, USA;5. Hospital of the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104, USA;6. Texas Health Presbyterian Dallas, 8200 Walnut Hill Lane, Dallas, TX 75231, USA;7. Division of General Internal Medicine, University of Connecticut, 263 Farmington Avenue, Farmington, CT, USA
Abstract:
Piperacillin/tazobactam (TZP) has been associated with nephrotoxicity in patients receiving vancomycin. Its impact on nephrotoxicity in patients with Gram-negative bacteraemia (GNB) is unclear. This study evaluated the impact of TZP on nephrotoxicity in patients with GNB. This retrospective cohort included patients aged ≥18 years receiving ≥48 h of therapy for bacteraemia due to Escherichia coli, Pseudomonas aeruginosa, Enterobacter, Klebsiella, Acinetobacter or Stenotrophomonas maltophilia from 1/01/2008–8/31/2011. Patients with baseline serum creatinine (SCr) ≥3.5 mg/dL, polymicrobial infection or recurrent bacteraemia were excluded. Nephrotoxicity was defined as a ≥0.5 mg/dL increase in SCr or ≥50% increase from baseline for ≥2 consecutive days. Any variable demonstrating a 10% change in exposure effect was retained in the final model. All variables biologically reasonable causes of nephrotoxicity were also considered for inclusion. The median age of the cohort (n?=?292) was 76 years; 38.0% had a cancer diagnosis and ICU residence was common (21.9%). There was no difference in nephrotoxicity incidence based on days of TZP received (0 days, 13.6%; 1–2 days, 14.7%; 3–4 days, 6.9%; ≥5 days, 16.7%; P?=?0.71). In multivariable analysis, baseline SCr, total body weight and vasopressor use were independently associated with nephrotoxicity. Duration of TZP was not associated with nephrotoxicity in multivariable analysis (1–2 days, OR?=?0.91, 95% CI 0.39–2.12; 3–4 days, OR?=?0.48, 95% CI 0.10–2.46; ≥5 days, OR?=?0.57, 95% CI 0.11–3.02). In this cohort of GNB patients, duration of TZP was not associated with nephrotoxicity.
Keywords:Nephrotoxicity  Piperacillin/tazobactam  Gram-negative bacteraemia  Acute kidney injury
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