In an adult with uncomplicated Enterobacter faecalis bacteremia whose blood cultures turned negative on day 7, how many days of piperacillin‑tazobactam (Zosyn) therapy should be given?

Duration of Piperacillin-Tazobactam for Uncomplicated Enterococcus faecalis Bacteremia

For uncomplicated Enterococcus faecalis bacteremia with negative blood cultures on day 7, complete a total of 7–14 days of piperacillin-tazobactam therapy, counting from the first day blood cultures turned negative. 1

Treatment Duration Framework

Counting Days of Therapy

• Begin counting the duration of antimicrobial therapy from the first day blood cultures are negative, not from the day treatment was initiated 1
• This approach is reasonable and supported by the American Heart Association for bloodstream infections that were initially culture-positive 1

Duration Based on Complexity

For uncomplicated bacteremia (7–14 days total): 1

• Patient meets all of the following criteria:
  • Endocarditis has been excluded
  • No implanted prostheses present
  • Follow-up blood cultures obtained 2–4 days after initial positive set are negative
  • Defervescence (fever resolution) within 72 hours of starting effective therapy
  • No evidence of metastatic sites of infection 1
• Most enterococcal bacteremias fall into this category and require 7–14 days of therapy 1

For complicated bacteremia (4–6 weeks): 1

• Any patient who does NOT meet all criteria for uncomplicated bacteremia
• Includes persistent fever beyond 72 hours, delayed blood culture clearance, or suspected metastatic foci
• Requires 4–6 weeks of therapy depending on extent of infection 1

Essential Monitoring Requirements

Blood Culture Follow-Up

• Obtain at least 2 sets of blood cultures every 24–48 hours until bloodstream infection has cleared 1
• This is critical to document clearance and ensure the infection is not complicated 1

Assessment for Complications

• Perform echocardiography (preferably transesophageal) to exclude endocarditis in all adult patients with bacteremia 1
• Conduct clinical assessment to identify the source and extent of infection, with elimination or debridement of other sites if present 1
• Look specifically for: implanted devices, valve vegetations, perivalvular abscess, metastatic foci (vertebral osteomyelitis, septic arthritis, visceral abscesses) 1

Critical Pitfalls to Avoid

Do Not Extend Therapy Unnecessarily

• If blood cultures are negative on day 7 and the patient meets all criteria for uncomplicated bacteremia, do not automatically extend to 4–6 weeks 1
• Prolonged unnecessary antibiotic exposure increases risk of adverse events, including Clostridioides difficile infection and drug toxicity 1

Do Not Stop Too Early

• Do not discontinue antibiotics before 7 days total even if the patient appears clinically well 1
• Enterococcal bacteremia requires adequate duration to prevent relapse 1

Recognize Piperacillin-Tazobactam Limitations

• Piperacillin-tazobactam is appropriate for Enterococcus faecalis but NOT for Enterococcus faecium, which is typically ampicillin-resistant 1
• If susceptibility testing reveals ampicillin resistance, switch to vancomycin or daptomycin 1
• Be aware that prolonged piperacillin therapy (>15 days) carries risk of neutropenia, though this is rare 2

Specific Recommendations for Your Case

Given that your patient has:

• Negative blood cultures on day 7 of piperacillin-tazobactam
• Enterococcus faecalis (typically ampicillin-susceptible)

Complete a total of 7–14 days of therapy from the first negative blood culture 1:

• If the patient is clinically stable, afebrile, and has no evidence of complications: 7–10 days total is reasonable 1
• If there was delayed clinical response or any concern for deeper infection: extend to 14 days total 1
• Ensure echocardiography has been performed to exclude endocarditis before stopping at 7–14 days 1