Can Zosyn (piperacillin/tazobactam) cause nephrotoxicity and hurt kidneys?

From the Guidelines

Zosyn (piperacillin/tazobactam) can cause nephrotoxicity and potentially harm the kidneys, although it is generally considered less nephrotoxic than some other antibiotics. The risk of nephrotoxicity is higher in patients who are elderly, have pre-existing kidney disease, are dehydrated, or are receiving other nephrotoxic medications simultaneously 1. According to the surviving sepsis campaign guidelines, patients with sepsis or septic shock have distinct differences from typical infected patients, including an increased frequency of hepatic and renal dysfunction, which affects the optimal antimicrobial management strategy 1.

Key Considerations

• The nephrotoxicity typically manifests as acute interstitial nephritis, an immune-mediated inflammatory reaction in the kidney tissue.
• Patients taking Zosyn should have their kidney function monitored regularly through blood tests measuring creatinine and BUN levels.
• Dose adjustments are necessary for patients with impaired kidney function, with typical adjustments ranging from 2.25g every 6 hours for mild impairment to 2.25g every 8 hours for more severe cases.
• The mechanism of Zosyn-induced kidney injury involves both direct tubular toxicity and immune-mediated hypersensitivity reactions.

Recommendations

• Monitor kidney function regularly in patients taking Zosyn, especially in those with pre-existing kidney disease or other risk factors for nephrotoxicity 1.
• Adjust doses according to kidney function to minimize the risk of nephrotoxicity.
• Consider alternative antibiotics if possible, especially in patients with severe kidney disease or other risk factors for nephrotoxicity.
• Prompt discontinuation of the medication and consultation with a healthcare provider is essential if kidney injury is suspected to prevent permanent damage.

From the FDA Drug Label

5.7 Nephrotoxicity in Critically Ill Patients The use of piperacillin and tazobactam for injection was found to be an independent risk factor for renal failure and was associated with delayed recovery of renal function as compared to other beta-lactam antibacterial drugs in a randomized, multicenter, controlled trial in critically ill patients [see Adverse Reactions (6. 1)]. Based on this study, alternative treatment options should be considered in the critically ill population. If alternative treatment options are inadequate or unavailable, monitor renal function during treatment with piperacillin and tazobactam for injection [see Dosage and Administration (2. 3)]. Combined use of piperacillin and tazobactam and vancomycin may be associated with an increased incidence of acute kidney injury [see Drug Interactions (7.3)].

Yes, Zosyn (piperacillin/tazobactam) can cause nephrotoxicity and hurt kidneys, especially in critically ill patients.

• The drug label warns of an increased risk of renal failure and delayed recovery of renal function compared to other beta-lactam antibacterial drugs.
• Alternative treatment options should be considered in critically ill patients, and renal function should be monitored during treatment with Zosyn.
• The combined use of Zosyn and vancomycin may also increase the risk of acute kidney injury 2.

From the Research

Zosyn and Kidney Damage

• Zosyn, a combination antibiotic consisting of piperacillin and tazobactam, has been reported to cause nephrotoxicity and hurt kidneys in some patients 3, 4, 5.
• A retrospective observational study found that the higher dose of piperacillin/tazobactam (4.5 g) was responsible for the decline in renal function, even if the dose frequency was reduced 3.
• Another study found that piperacillin/tazobactam was associated with a higher risk of acute kidney injury (AKI) compared to alternative antibiotics 4.
• A case report described a patient with end-stage renal disease who developed rapid-onset thrombocytopenia after receiving Zosyn, highlighting the importance of vigilance for drug-induced thrombocytopenia in patients receiving Zosyn 6.
• A study using a mouse model found that piperacillin/tazobactam caused direct nephrotoxicity, associated with oxidative stress and mitochondrial damage in the kidney tubular cells 5.

Risk Factors for Nephrotoxicity

• Patients with pre-existing renal impairment are at higher risk of developing nephrotoxicity when treated with Zosyn 3, 7.
• The dose and frequency of Zosyn administration can also impact the risk of nephrotoxicity, with higher doses and more frequent administration increasing the risk 3, 7.
• Combination therapy with vancomycin may also increase the risk of AKI in patients treated with Zosyn 4.

Monitoring and Prevention

• Patients receiving Zosyn should be closely monitored for signs of nephrotoxicity, including changes in renal function and electrolyte imbalances 3, 7.
• Dose adjustment and hydration may be necessary to prevent or mitigate nephrotoxicity in patients at high risk 3, 7.
• Alternative antibiotics may be considered for patients at high risk of AKI or with pre-existing renal impairment 4.