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Piperacillin / tazobactam

Class
Antibiotics
Subclass
Penicillin / β-lactamase inhibitor combination
Substance name
Piperacillin / tazobactam
Brand names
Zosyn®
Contains
Piperacillin
Tazobactam sodium
Common formulations
Solution for injection
Dosage and administration
Adults patients
Acute appendicitis • Complicated
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Community-acquired pneumonia
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Endometritis
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Hospital-acquired pneumonia
•
4.5 g IV q6h over 30 minutes for 7-14 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-14 days
Intra-abdominal infections
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Pelvic inflammatory disease
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Peritonitis
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h (extended infusion) for 7-10 days
SSTIs
•
3.375 g IV q6h over 30 minutes for 7-10 days
Alternative
•
Loading: 4.5 g IV × 1 over 30 minutes
•
Maintenance: 4.5 g IV q8h, each dose administered over 4 hours (extended infusion), for 7-10 days
Acute diverticulitis • Off-label
•
3.375 g IV q6h
Bronchiectasis • Off-label
•
4/0.5 g IV q8h for 14 days
Diabetic foot ulcer • Off-label
•
3.375 g IV q6h
Other off-label uses
•
Treatment of anthrax (inhalational)
•
Treatment of bite wound infection (animal or human)
•
Treatment of cystic fibrosis
•
Treatment of febrile neutropenia
•
Treatment of necrotizing fasciitis
•
Treatment of sepsis
•
Treatment of surgical site infection
•
Treatment of UTIs
Indications for use
Labeled indications
Adults
•
Treatment of acute appendicitis (complicated)
•
Treatment of community-acquired pneumonia
•
Treatment of endometritis
•
Treatment of gynecologic and pelvic infections in females (postpartum endomyometritis)
•
Treatment of hospital-acquired pneumonia
•
Treatment of intra-abdominal infections
•
Treatment of pelvic inflammatory disease
•
Treatment of peritonitis
•
Treatment of SSTIs
Off-label indications
Adults
•
Treatment of acute diverticulitis
•
Treatment of anthrax (inhalational)
•
Treatment of bite wound infection (animal or human)
•
Treatment of bronchiectasis
•
Treatment of cystic fibrosis
•
Treatment of diabetic foot ulcer
•
Treatment of febrile neutropenia
•
Treatment of necrotizing fasciitis
•
Treatment of sepsis
•
Treatment of surgical site infection
•
Treatment of UTIs
Safety risks
Contraindications
Hypersensitivity to any of the penicillins, cephalosporins, or β-lactamase inhibitors
Warnings and precautions
Bleeding, prolonged clotting times, prolonged PT
•
Use caution in patients with renal failure.
C. difficile infection
•
Maintain a high level of suspicion as antibiotic use could increase of C. difficile infection ranging from mild diarrhea to severe colitis.
Exacerbation of seizures
•
Use caution in patients with a history of seizure disorder.
Hemophagocytic lymphohistiocytosis
•
Maintain a high level of suspicion for signs and symptoms of HLH such as fever, rash, lymphadenopathy, hepatosplenomegaly and cytopenia.
Hypernatremia
•
Use caution in patients requiring restricted salt intake.
Nephrotoxicity, AKI
•
Use caution in critically ill patients.
Pseudomembranous colitis
•
Use caution in patients presenting with diarrhea after antibacterial use.
Rhabdomyolysis
•
Maintain a high level of suspicion for signs and symptoms of muscle pain, tenderness or weakness, darkened urine or elevated creatine phosphokinase.
Stevens-Johnson syndrome, DRESS syndrome, toxic epidermal necrolysis
•
Maintain a high level of suspicion, as piperacillin/tazobactam is associated with severe hypersensitivity reactions.
Specific populations
Renal impairment
CrCl 40-50 mL/min
•
Use acceptable. No dose adjustment required. Monitor for neuromuscular excitability and convulsions.
CrCl 20-40 mL/min
•
Maximal dose of 2.25g. Do not exceed frequency of q6h. Monitor for neuromuscular excitability and convulsions. For nosocomial pneumonia ONLY: Reduce dose to 3.375g every 6 hours.
CrCl < 20 mL/min
•
Maximal dose of 2.25 g. Do not exceed frequency of q8h. Monitor for neuromuscular excitability and convulsions. For nosocomial pneumonia ONLY: Reduce dose to 2.25g every 6 hours.
Renal replacement therapy
Continuous renal replacement
•
Dose as in eGFR < 20 mL/min/1.73 m². Maximal dose of 2.25g. Maximal frequency of q6h. Monitor for neuromuscular excitability and convulsions.
Intermittent hemodialysis
•
Dose as in eGFR < 20 mL/min/1.73 m². Maximal dose of 2.25g. Maximal frequency of q12h. Monitor for neuromuscular excitability and convulsions. For nosocomial pneumonia ONLY: Reduce dose to 2.25g every 8 hours. Since hemodialysis removes 30% to 40% of the administered dose, an additional dose of 0.75 g should be given after each dialysis period on dialysis days.
Peritoneal dialysis
•
Dose as in eGFR < 20 mL/min/1.73 m². Maximal dose of 2.25g. Maximal frequency of q12h. Monitor for neuromuscular excitability and convulsions. For nosocomial pneumonia ONLY: Reduce dose to 2.25g every 8 hours.
Hepatic impairment
Any severity
•
Use acceptable. No dose adjustment required. Monitor serum aminotransferases. Monitor for toxicity.
Pregnancy and breastfeeding
Pregnancy
All trimesters • Australia Category: B1
•
Generally acceptable for use. Evidence of fetal harm in animals. Use is generally considered compatible in pregnancy.
Breastfeeding
Use only if benefits outweigh potential risks.
Unknown amount excreted in breastmilk.
Unknown drug levels in breastfed infants.
Adverse reactions
Very common > 10%
•
Allergic reactions, ↓ blood neutrophil count, diarrhea
Common 1-10%
•
Anaphylaxis, anemia, candidiasis, ↓ blood glucose, ↓ platelet count, ↓ serum potassium, hypotension, ↑ BUN, ↑ liver enzymes, ↑ platelet count, ↑ serum creatinine, oral candidiasis, ⊕ direct Coombs test, pseudomembranous colitis, renal failure, abdominal pain, arthralgia, constipation, fever, generalized pruritus, headache, indigestion, injection site reactions, insomnia, myalgia, nausea, nosebleed, rigors, skin flushing, skin rash, urethral pruritus, vomiting, stomatitis, thrombophlebitis
Unknown frequency
•
Acute generalized exanthematous pustulosis, agranulocytosis, coagulation disorder, DRESS syndrome, ↓ WBC count, ↓ hematocrit, ↓ hemoglobin, encephalopathy, erythema multiforme, erythroderma, hemolytic anemia, hemophagocytic lymphohistiocytosis, hepatitis, jaundice, pancytopenia, petechiae, pulmonary eosinophilia, paresthesia, seizure, shock, Stevens-Johnson syndrome, toxic epidermal necrolysis, tubulointerstitial nephritis
Interactions
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