From the Guidelines
Zosyn (piperacillin-tazobactam) is an appropriate choice for empiric treatment of sepsis, particularly in hospitalized patients, as it provides broad-spectrum coverage against many gram-positive, gram-negative, and anaerobic bacteria. The typical adult dosing is 3.375g or 4.5g IV every 6-8 hours, with adjustments needed for renal impairment, as recommended by the Surviving Sepsis Campaign guidelines 1. Zosyn is particularly valuable when the source is suspected to be intra-abdominal, urinary, respiratory, or skin/soft tissue infections. However, the appropriateness depends on several factors including:
- The suspected source of infection
- Local antibiotic resistance patterns
- Patient allergies
- Prior antibiotic exposure Zosyn may not provide adequate coverage for MRSA, resistant Pseudomonas, or certain ESBL-producing organisms, so additional agents might be needed based on risk factors, as suggested by the guidelines 1. Some key points to consider when using Zosyn for sepsis treatment include:
- Treatment should be initiated promptly within one hour of sepsis recognition, as recommended by the guidelines 1
- De-escalation to narrower-spectrum antibiotics should occur once culture results are available, typically within 48-72 hours
- Blood cultures and other relevant specimens should be collected before starting antibiotics whenever possible, but should not delay timely antibiotic administration, as emphasized by the guidelines 1.
From the FDA Drug Label
Piperacillin and tazobactam has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections [see Indications and Usage (1)]
The use of Zosyn (piperacillin-tazobactam) for a patient with triggered sepsis is appropriate if the sepsis is caused by susceptible microorganisms. However, the specific causative pathogen and its susceptibility to piperacillin-tazobactam should be confirmed whenever possible.
- Key considerations:
- Broad-spectrum activity: Piperacillin-tazobactam has broad-spectrum activity against many gram-positive and gram-negative aerobic and anaerobic bacteria.
- Empiric therapy: It can be used as empiric therapy for sepsis, but de-escalation to a more targeted therapy should occur once the causative pathogen and its susceptibility are known.
- Dosing and administration: The dosage and administration of piperacillin-tazobactam should be according to the FDA-approved labeling and institutional guidelines. 2
From the Research
Appropriateness of Zosyn for Sepsis
- Zosyn, also known as piperacillin-tazobactam, is a broad-spectrum antibiotic used to treat various bacterial infections, including those that cause sepsis 3.
- The use of piperacillin-tazobactam in sepsis patients has been studied, and the results suggest that it can be an effective treatment option 4, 5, 6.
- A study published in 2023 found that piperacillin-tazobactam dose reduction in early phase septic shock is associated with worsened clinical outcomes, highlighting the importance of appropriate dosing 4.
- Another study from 2019 investigated the use of therapeutic drug monitoring (TDM) to optimize piperacillin-tazobactam dosing in sepsis patients, with the goal of improving clinical outcomes 5.
- A 2022 randomized controlled trial found that TDM-guided therapy showed no significant difference in mean SOFA score, but patients with TDM-guided therapy had a lower 28-day mortality and a higher rate of clinical and microbiological cure, although these differences did not reach statistical significance 6.
Administration and Dosing
- The administration of piperacillin-tazobactam can be done through intravenous push (IVP) or intravenous piggyback (IVPB), with IVP being associated with a reduction in time to antibiotic administration in emergency department patients with sepsis 7.
- The dosing of piperacillin-tazobactam is crucial, and studies have shown that adequate dosing is essential to achieve optimal clinical outcomes in sepsis patients 4, 6.
Clinical Outcomes
- The clinical outcomes of sepsis patients treated with piperacillin-tazobactam have been evaluated in several studies, with results suggesting that it can be an effective treatment option 4, 5, 3, 6.
- A study from 1999 found that piperacillin-tazobactam was effective in treating various infections, including those caused by Gram-positive and Gram-negative bacteria 3.