Piperacillin/Tazobactam Use vs Cefepime May Be Associated With Acute Decompensated Heart Failure
Background: Piperacillin/tazobactam (PTZ) has been cautiously used or avoided in patients with a history of heart disease due to concern for heart failure (HF) exacerbation given its relatively high sodium content. However, no prior studies have established this association.
Methods: The Antimicrobial Stewardship Team at the James H. Quillen Veterans Affairs Medical Center reviewed the use of PTZ vs the comparator antibiotic, cefepime, in 2 consecutive years to determine whether the use of PTZ was more likely to be associated with acute decompensation of HF. Records of 389 veterans hospitalized in 2018 and 2019 were reviewed and included in this study.
Results: Acute decompensation of HF was significantly associated with the use of PTZ (n = 25; 12.3%) compared with cefepime (n = 4; 2.2%) (P < .001). Additionally, hospital readmissions due to HF were higher in the PTZ group compared with the cefepime group (11 vs 1, P = .02). There were no significant differences identified in the length of stay or overall mortality between 204 patients who received PTZ compared with 185 patients who received cefepime (P = .54 and P = .63, respectively).
Conclusions: PTZ use was significantly associated with a higher incidence of acute decompensation of HF and hospital readmission with HF exacerbation compared with cefepime. PTZ use among hospitalized patients with a history of HF should be carefully monitored or avoided.
Piperacillin/tazobactam (PTZ) is a combination IV antibiotic comprised of the semisynthetic antipseudomonal β-lactam, piperacillin sodium, and the β-lactamase inhibitor, tazobactam sodium.1 PTZ is extensively prescribed in the hospital setting for a multitude of infections including but not limited to the US Food and Drug Administration–approved indications: intra-abdominal infection, skin and skin structure infection (SSTI), urinary tract infection (UTI), and pneumonia. Given its broad spectrum of activity and relative safety profile, PTZ is a mainstay of many empiric IV antibiotic regimens. The primary elimination pathway for PTZ is renal excretion, and dosage adjustments are recommended with reduced creatinine clearance. Additionally, PTZ use has been associated with acute renal injury and delayed renal recovery.1-3
There are various mechanisms through which medications can contribute to acute decomopensated heart failure (ADHF).4 These mechanisms include direct cardiotoxicity; negative inotropic, lusitropic, or chronotropic effects; exacerbating hypertension; sodium loading; and drug-drug interactions that limit the benefits of heart failure (HF) medications. One potentially overlooked constituent of PTZ is the sodium content, with the standard formulation containing 65 mg of sodium per gram of piperacillin.1-3 Furthermore, PTZ must be diluted in 50 to 150 mL of diluent, commonly 0.9% sodium chloride, which can contribute an additional 177 to 531 mg of sodium per dose. PTZ prescribing information advises caution for use in patients with decreased renal, hepatic, and/or cardiac function and notes that geriatric patients, particularly with HF, may be at risk of impaired natriuresis in the setting of large sodium doses.
It is estimated that roughly 6.2 million adults in the United States have HF and prevalence continues to rise.5,6 Mortality rates after hospitalization due to HF are 20% to 25% at 1 year. Health care expenditures for the management of HF surpass $30 billion per year in the US, with most of this cost attributed to hospitalizations. Consequently, it is important to continue to identify and practice preventative strategies when managing patients with HF.
Methods
This single-center, retrospective, cohort study was conducted at James H. Quillen Veterans Affairs Medical Center (JHQVAMC) in Mountain Home, Tennessee, a 174-bed tertiary medical center. The purpose of this study was to compare the incidence of ADHF in patients who received PTZ vs cefepime (CFP). This project was reviewed by the JHQVAMC Institutional Review Board and deemed exempt as a clinical process improvement operations activity.
The antimicrobial stewardship team at JHQVAMC reviewed the use of PTZ in veterans between January 1, 2018, to December 31, 2019, and compared baseline demographics, history of HF, and outcomes in patients receiving analogous broad-spectrum empiric antibiotic therapy with CFP.
Statistical Analysis
Analysis was conducted with R Software. Pearson χ2 and t tests were used to compare baseline demographics, length of stay, readmission, and mortality. Significance used was α = .05.
