What is the recommended dosage and treatment guidelines for piperacillin/tazobactam (Tazact) in patients with infections and potentially Impaired renal function?

From the Guidelines

Piperacillin/tazobactam (Tazact) dosing should be adjusted based on renal function, with the standard adult dose being 4.5g (4g piperacillin/0.5g tazobactam) administered intravenously every 6-8 hours for patients with normal renal function. For patients with impaired renal function, dosage adjustments are necessary:

• for creatinine clearance 20-40 mL/min, give 4.5g every 8 hours;
• for clearance <20 mL/min, give 4.5g every 12 hours;
• and for hemodialysis patients, give 2.25g every 8 hours plus an additional 0.75g after each dialysis session 1. Treatment duration typically ranges from 7-14 days depending on infection severity and site.
• Monitor renal function regularly during treatment, as the medication can cause further kidney damage.
• Assess clinical response within 48-72 hours of initiating therapy. These adjustments are crucial because piperacillin/tazobactam is primarily eliminated by the kidneys, and impaired renal function leads to drug accumulation, potentially causing toxicity including neurotoxicity and electrolyte disturbances if not properly dosed. The most recent guidelines from 2020 recommend piperacillin/tazobactam 4.5 g 6-hourly for empiric antibiotic regimens in critically ill patients with intra-abdominal infections and normal renal function 1. Additionally, the 2017 WSES guidelines for management of intra-abdominal infections also recommend piperacillin/tazobactam 4.5 g 6-hourly for critically ill patients 1. It is essential to note that these recommendations prioritize morbidity, mortality, and quality of life as outcomes, and the dosage adjustments are critical to prevent potential toxicity and ensure effective treatment.

From the FDA Drug Label

2.3 Dosage in Adult Patients with Renal Impairment

The recommended dosage for piperacillin/tazobactam (Tazact) in patients with infections and potentially impaired renal function is as follows:

• CrCl ≥ 40 mL/min: No dosage adjustment is necessary.
• CrCl 20-40 mL/min: Dosage should be reduced to 2.25 g every 6 hours.
• CrCl < 20 mL/min: Dosage should be reduced to 2.25 g every 8 hours.
• Hemodialysis: Dosage should be reduced to 2.25 g every 12 hours, with an additional dose of 0.75 to 1.25 g after each dialysis period, depending on the severity of the infection 2. It is essential to monitor renal function and adjust the dosage accordingly to avoid toxicity.

From the Research

Dosage and Treatment Guidelines for Piperacillin/Tazobactam (Tazact)

• The recommended dosage and treatment guidelines for piperacillin/tazobactam (Tazact) in patients with infections and potentially impaired renal function are not explicitly stated in the provided studies.
• However, the studies suggest that piperacillin/tazobactam is effective in treating various infections, including lower respiratory tract, intra-abdominal, urinary tract, gynaecological, and skin/soft tissue infections, as well as fever in patients with neutropenia 3, 4, 5, 6, 7.
• The combination of piperacillin/tazobactam with an aminoglycoside is used to treat patients with severe nosocomial infections 3.
• In patients with impaired renal function, the dosage of piperacillin/tazobactam may need to be adjusted to avoid accumulation of the drug and its metabolites 4.

Efficacy of Piperacillin/Tazobactam in Various Infections

• Piperacillin/tazobactam has been shown to be effective in treating intra-abdominal infections, with clinical cure rates ranging from 88% to 91% 5, 7.
• The combination of piperacillin/tazobactam with amikacin has been shown to be effective in treating febrile neutropenic episodes, with clinical cure rates ranging from 87% to 93% 3, 4.
• Piperacillin/tazobactam has also been shown to be effective in treating skin and soft tissue infections, with clinical cure rates ranging from 74% to 87% 5, 6.

Safety and Tolerability of Piperacillin/Tazobactam

• Piperacillin/tazobactam is generally well-tolerated, with the most frequent adverse events being gastrointestinal symptoms and skin reactions 3, 4, 5.
• The incidence of adverse events with piperacillin/tazobactam is higher when the combination is given with an aminoglycoside than when given as monotherapy 3.