Does Zosyn (piperacillin/tazobactam) cover Gram-negative rods?

From the Guidelines

Zosyn (piperacillin/tazobactam) is effective against gram-negative rod bacteria, including Pseudomonas aeruginosa, Escherichia coli, Klebsiella species, Enterobacter, Proteus, and other Enterobacteriaceae, as supported by the most recent and highest quality study 1.

Key Points

• Zosyn is a combination antibiotic consisting of piperacillin, an extended-spectrum penicillin, and tazobactam, a beta-lactamase inhibitor that prevents bacterial enzymes from inactivating piperacillin.
• The typical adult dosing is 3.375g or 4.5g IV every 6-8 hours, with adjustments needed for renal impairment, as recommended in the 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society 1.
• Zosyn works by inhibiting bacterial cell wall synthesis, causing cell death, and its broad spectrum of activity makes it valuable for treating serious infections like intra-abdominal infections, pneumonia, complicated skin infections, and febrile neutropenia.
• However, increasing resistance among some gram-negative organisms is a concern, particularly with extended-spectrum beta-lactamase (ESBL) producing bacteria, which may require alternative therapies, as noted in the 2018 WSES/SIS-E consensus conference recommendations 1.

Considerations

• The use of piperacillin-tazobactam is appropriate in settings without a high local prevalence of ESBL-producing Enterobacteriaceae, optimizing pharmacokinetic/pharmacodynamic parameters 1.
• In settings with a high local prevalence of ESBL-producing Enterobacteriaceae, carbapenems, such as meropenem, imipenem-cilastatin, or doripenem, may be used as an alternative therapy 1.
• Culture-specific results and sensitivities can direct both broadening of antimicrobial regimen if it is too narrow, and procalcitonin monitoring may be useful to guide antimicrobial discontinuation 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)] Aerobic bacteria Gram-positive bacteria Staphylococcus aureus (methicillin susceptible isolates only) Gram-negative bacteria Acinetobacter baumannii Escherichia coli Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates) Klebsiella pneumoniae Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)

Yes, Zosyn (piperacillin/tazobactam) covers Gram-negative rods, including:

• Acinetobacter baumannii
• Escherichia coli
• Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates)
• Klebsiella pneumoniae
• Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible) 2

From the Research

Coverage of Gram-Negative Rods by Zosyn (Piperacillin/Tazobactam)

• Zosyn (piperacillin/tazobactam) has been shown to be effective against various Gram-negative rods, including Pseudomonas aeruginosa 3, 4, 5.
• The antibiotic combination has a broad spectrum of antibacterial activity, encompassing most Gram-positive and Gram-negative aerobic bacteria and anaerobic bacteria, including many pathogens producing beta-lactamases 6.
• Studies have demonstrated that piperacillin/tazobactam is active against Escherichia coli and Klebsiella pneumoniae, including strains that produce extended-spectrum beta-lactamases (ESBL) 5, 7.
• However, the potency of piperacillin/tazobactam may be reduced against certain resistant organism populations, such as carbapenem-resistant Pseudomonas aeruginosa, and higher doses or extended infusion may be necessary to optimize exposure 4.

Specific Gram-Negative Rods Covered by Zosyn

• Pseudomonas aeruginosa: piperacillin/tazobactam has been shown to be effective against this organism, including strains that are resistant to imipenem 3, 4, 5.
• Escherichia coli: piperacillin/tazobactam is active against E. coli, including strains that produce ESBL 5, 7.
• Klebsiella pneumoniae: piperacillin/tazobactam is active against K. pneumoniae, including strains that produce ESBL 5, 7.
• Haemophilus influenzae: piperacillin/tazobactam is active against H. influenzae, including strains that are resistant to ampicillin 5.