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. Patients were included if they received at least 24 hours of PTZ or CFP. Patients were excluded if they were diagnosed with ADHF before initiation of antibiotic therapy. Patients with ADHF were identified by clinical diagnosis of ADHF documented by the treating clinician and reaffirmed by the study clinician during retrospective chart review. Clinical information used to determine ADHF included clinical presentation, imaging (ie, chest X-ray, echocardiograms), and laboratory parameters, such as B-type natriuretic peptide. The primary endpoint of this study was the incidence of ADHF during the current hospitalization. Secondary endpoints included the length of hospital stay, hospital readmission, and overall mortality. Patient chart reviews were performed using the JHQVAMC Computerized Patient Record System (CPRS).
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.