Is Zosyn (piperacillin/tazobactam) effective for treating Escherichia coli (E. coli) bacteremia?

From the Guidelines

Zosyn (piperacillin-tazobactam) is a suitable treatment option for E. coli bloodstream infections, as evidenced by the ESCMID guidelines 1. When considering treatment for E. coli bloodstream infections, it is essential to prioritize morbidity, mortality, and quality of life. The recommended dosage of Zosyn is 4.5 grams (4 g piperacillin/0.5 g tazobactam) administered intravenously every 6-8 hours, with adjustment needed for patients with renal impairment.

Some key points to consider when using Zosyn for E. coli bloodstream infections include:

• The mechanism of action, where piperacillin disrupts bacterial cell wall synthesis, and tazobactam inhibits beta-lactamase enzymes that some E. coli strains produce to resist beta-lactam antibiotics.
• The importance of obtaining blood cultures before starting Zosyn and narrowing therapy to a more targeted antibiotic once susceptibility results are available.
• Monitoring patients for clinical improvement, repeat blood cultures to confirm clearance of infection, and potential side effects including allergic reactions, gastrointestinal disturbances, and electrolyte abnormalities.
• The need for additional supportive measures in cases of severe sepsis or septic shock alongside antibiotic therapy.

It is crucial to note that while Zosyn is an effective treatment option, other antibiotics, such as intravenous fosfomycin, plazomicin, and aminoglycosides, may also be considered based on the specific clinical scenario and patient factors, as discussed in the ESCMID guidelines 1. However, Zosyn remains a viable choice for E. coli bloodstream infections, particularly when used appropriately and with careful patient monitoring.

From the FDA Drug Label

1. 4 Female Pelvic Infections Piperacillin and Tazobactam for Injection is indicated in adults for the treatment of postpartum endometritis or pelvic inflammatory disease caused by beta-lactamase producing isolates of Escherichia coli.

The answer to the use of Zosyn (piperacillin-tazobactam) for E. coli blood cultures is that it is indicated for the treatment of infections caused by beta-lactamase producing isolates of Escherichia coli, but the label does not specifically mention blood cultures. However, based on the information provided, Zosyn can be used to treat infections caused by E. coli, including those that may be present in the blood, as long as the isolate is beta-lactamase producing. Key points to consider:

• Indication: Treatment of infections caused by beta-lactamase producing isolates of Escherichia coli.
• Usage: To reduce the development of drug-resistant bacteria and maintain the effectiveness of Piperacillin and Tazobactam for Injection and other antibacterial drugs, piperacillin and tazobactam should be used only to treat or prevent infections that are proven or strongly suspected to be caused by bacteria 2.

From the Research

Zosyn (Piperacillin/Tazobactam) for E. coli Blood Cultures

• Zosyn is a combination antibiotic consisting of piperacillin and tazobactam, used to treat various bacterial infections, including those caused by E. coli 3, 4, 5, 6, 7.
• The effectiveness of Zosyn for E. coli blood cultures depends on the susceptibility of the E. coli strain to piperacillin/tazobactam, as well as the presence of extended-spectrum beta-lactamases (ESBL) or other resistance mechanisms 3, 4, 5, 6.
• Studies have shown that Zosyn can be effective against E. coli strains that are susceptible to piperacillin/tazobactam, including those with ESBL-producing strains 5, 7.
• However, the use of Zosyn may be associated with reduced early treatment response in E. coli blood cultures caused by ampicillin/sulbactam-resistant isolates compared to alternative monotherapies 3.
• The development of resistance to Zosyn during treatment is a concern, and can occur through various mechanisms, including the hyperproduction of beta-lactamases 6.

Treatment Outcomes

• Clinical success, 28-day mortality, and rate of relapsing BSI did not significantly differ between patients treated with Zosyn and those treated with alternative monotherapies 3.
• The overall clinical cure rate with Zosyn was achieved in 89.4% of patients with E. coli infections, with the best results in urinary tract infections (100%) and soft tissue infections (80%) 5.
• Aminoglycosides were found to be non-inferior to carbapenems or Zosyn for the treatment of bloodstream infections of urinary source caused by ESBL-producing Enterobacteriaceae, including E. coli 7.

Resistance Mechanisms

• The development of resistance to Zosyn can occur through various mechanisms, including the production of beta-lactamases that are not inhibited by tazobactam 6.
• The hyperproduction of beta-lactamases, such as TEM-1, can lead to resistance to Zosyn, even in strains that are initially susceptible 6.
• The use of Zosyn can select for resistant strains, including those with ESBL-producing strains, which can limit its effectiveness 4, 7.