piperacillin/tazobactam

Piperacillin

Binds to bacterial cell wall membrane, causing cell death. Spectrum is extended compared with other penicillins.

Tazobactam

Inhibits beta-lactamase, an enzyme that can destroy penicillins.

Therapeutic effects:

Death of susceptible bacteria.

Spectrum:

Active against piperacillin-resistant, beta-lactamase–producing:
- Bacteroides fragilis,
- E. coli,
- Acinetobacter baumanii,
- Klebsiella pneumoniae,
- Pseudomonas aeruginosa,
- Staphylococcus aureus,
- Haemophilus influenzae.

Pharmacokinetics ⬆ ⬇

Absorption: IV administration results in complete bioavailability.

Distribution: Widely distributed. Enters CSF well only when meninges are inflamed.

Metabolism/Excretion: Piperacillin (68%) and tazobactam (80%) are mostly excreted unchanged by the kidneys.

Half-Life: Adults: 0.7–1.2 hr; Children (6 mo–12 yr): 0.7–0.9 hr; Infants (2–5 mo): 1.4 hr.

Time/Action Profile ⬆ ⬇

(piperacillin plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
IV	rapid	end of infusion	4–6 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity to penicillins, beta-lactams, cephalosporins, or tazobactam (cross-sensitivity may occur).

Use Cautiously in:

Renal impairment (↑ risk of seizures) (dosage ↓ or increased interval recommended if CCr <40 mL/min);
Seizure disorders
Sodium restriction;
Critically ill patients (↑ risk of renal failure; use alternative antibiotic, if possible);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children 2 mo (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

Derm: rash (↑ in patients with cystic fibrosis), ACUTE GENERALIZED EXANTHEMATOUS PUSTULOSIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS, urticaria

GI: diarrhea, CLOSTRIDIOIDES DIFFICILE-ASSOCIATED DIARRHEA (CDAD), constipation, drug-induced hepatitis, nausea, vomiting

GU: interstitial nephritis, renal failure

Hemat: bleeding, leukopenia, neutropenia, thrombocytopenia

Local: pain, phlebitis at IV site

Neuro: confusion, dizziness, headache, insomnia, lethargy, SEIZURES (HIGHER DOSES)

Misc: fever (↑ in cystic fibrosis patients), hemophagocytic lymphohistiocytosis, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND SERUM SICKNESS), superinfection

Interactions ⬆ ⬇

Drug-drug:

Probenecid↓ renal excretion and ↑ blood levels.
May alter excretion of lithium.
Potassium-losing diuretics, corticosteroids, or amphotericin B may ↑ risk of hypokalemia.
↑risk of hepatotoxicity with other hepatotoxic agents.
May ↓ levels/effects of aminoglycosides in patients with renal impairment.
May ↑ levels and risk of toxicity from methotrexate.
↑risk of acute kidney injury when concomitantly administered with vancomycin.
May prolong the neuromuscular blockade associated with vecuronium.

Route/Dosage ⬆ ⬇

Contains 2.84 mEq (65 mg) sodium/g of piperacillin; adult doses below expressed as combined piperacillin/tazobactam content

Appendicitis/Peritonitis

IV (Adults and Children ≥2 mo and >40 kg): 3.375 g every 6 hr.
IV (Children ≥9 mo and ≤40 kg and normal renal function): 112.5 mg (100 mg piperacillin/12.5 mg tazobactam)/kg every 8 hr.
IV (Infants 2–9 mo and ≤40 kg and normal renal function): 90 mg (80 mg piperacillin/10 mg tazobactam)/kg every 8 hr.

Renal Impairment

IV (Adults ): CCr 20–40 mL/min: 2.25 g every 6 hr; CCr <20 mL/min: 2.25 g every 8 hr; Hemodialysis: 2.25 g every 12 hr + 0.75 g following hemodialysis on hemodialysis days; Continuous ambulatory peritoneal dialysis: 2.25 g every 12 hr.

Nosocomial Pneumonia

IV (Adults and Children ≥2 mo and >40 kg): 4.5 g every 6 hr.
IV (Children ≥9 mo and ≤40 kg and normal renal function): 112.5 mg (100 mg piperacillin/12.5 mg tazobactam)/kg every 6 hr.
IV (Infants 2–9 mo and ≤40 kg and normal renal function): 90 mg (80 mg piperacillin/10 mg tazobactam)/kg every 6 hr.

Renal Impairment

IV (Adults ): CCr 20–40 mL/min: 3.375 g every 6 hr; CCr <20 mL/min: 2.25 g every 6 hr; Hemodialysis: 2.25 g every 8 hr + 0.75 g following hemodialysis on hemodialysis days; Continuous ambulatory peritoneal dialysis: 2.25 g every 8 hr.

Skin and Skin Structure Infections, Gynecologic Infections, and Community-Acquired Pneumonia

IV (Adults ): 3.375 g every 6 hr.

Renal Impairment

IV (Adults ): CCr 20–40 mL/min: 2.25 g every 6 hr; CCr <20 mL/min: 2.25 g every 8 hr; Hemodialysis: 2.25 g every 12 hr + 0.75 g following hemodialysis on hemodialysis days; Continuous ambulatory peritoneal dialysis: 2.25 g every 12 hr.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 2.25 g (2 g piperacillin/0.25 g tazobactam)/vial; 3.375 g (3 g piperacillin/0.375 g tazobactam)/vial; 4.5 g (4 g piperacillin/0.5 g tazobactam)/vial; 13.5 g (12 g piperacillin/1.5 g tazobactam)/vial; 40.5 g (36 g piperacillin/4.5 g tazobactam)/vial
Premixed infusion: 2.25 g (2 g piperacillin/0.25 g tazobactam) in 50 mL; 3.375 g (3 g piperacillin/0.375 g tazobactam) in 50 mL; 4.5 g (4 g piperacillin/0.5 g tazobactam) in 100 mL

Assessment ⬆ ⬇

Assess patient for infection (vital signs; appearance of wound, sputum, urine, and stool; WBC) at beginning of and during therapy.
Obtain a history before initiating therapy to determine previous use of and reactions to penicillins or cephalosporins. Persons with a negative history of penicillin sensitivity may still have an allergic response.
Obtain specimens for culture and sensitivity prior to initiating therapy. 1st dose may be given before receiving results.
Observe patient for signs and symptoms of anaphylaxis (rash, pruritus, laryngeal edema, wheezing). Discontinue the drug and notify health care professional immediately if these occur. Keep epinephrine, an antihistamine, and resuscitation equipment close by in the event of an anaphylactic reaction.
Monitor bowel function. Diarrhea, abdominal cramping, fever, and bloody stools should be reported to health care professional promptly as a sign of CDAD. May begin up to several wk following cessation of therapy.
Assess for skin reactions (rash, fever, edema, mucosal erosions or ulcerations, red or inflamed eyes). Monitor patient with mild to moderate rash for progression. If rash becomes severe or systemic symptoms occur, discontinue piperacillin/tazobactam.
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling), associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.
Monitor for signs and symptoms of hemophagocytic lymphohistiocytosis (fever, rash, lymphadenopathy, hepatosplenomegaly, cytopenia); if these occur suspected, discontinue piperacillin/tazobactam immediately and treat as needed.

Lab Test Considerations:

Evaluate renal and hepatic function, CBC, serum potassium, and bleeding times prior to and routinely during therapy.
- May cause positive direct Coombs’ test result.
- May cause ↑ BUN, serum creatinine, AST, ALT, serum bilirubin, alkaline phosphatase, and LDH.
- May cause leukopenia and neutropenia, especially with prolonged therapy or hepatic impairment.
- May cause prolonged prothrombin and partial thromboplastin time.
- May cause ↓ hemoglobin and hematocrit and thrombocytopenia, eosinophilia, leukopenia, and neutropenia. It also may cause proteinuria; hematuria; pyuria; hyperglycemia; ↓ total protein or albumin; and abnormalities in sodium, potassium, and calcium concentrations.

Implementation ⬆ ⬇

IV Administration:

If a dose of piperacillin/tazobactam is required that does not equal 2.25 g, 3.375 g, or 4.5 g, premixed infusion should not be used.
Intermittent Infusion: For patients weighing >40 kg:Reconstitution: Reconstitute 2.25 g, 3.375 g, and 4.5 g single-dose vials with 10 mL, 15 mL, and 20 mL, respectively of 0.9% NaCl, Sterile Water for Injection, or D5W. Swirl until dissolved.Concentration: 202.5 mg/mL (180 mg/mL of piperacillin and 22.5 mg/mL of tazobactam).Diluent: Dilute further in 50–150 mL of 0.9% NaCl, D5W, D6/0.9% NaCl, or LR. For patients weighing up to 40 kg: dilute to a concentration of 20 mg/mL to 80 mg/mL. Reconstituted vials stable for 24 hr at room temperature or 48 hr if refrigerated. Infusion stable for 24 hr at room temperature or 7 days if refrigerated. Premixed bags are stable for 24 hr at room temperature of 14 days if refrigerated.
Rate: Infuse over 30 min.

Patient/Family Teaching ⬆ ⬇

Explain purpose of piperacillin/tazobactam to patient.
Advise patient to report rash and signs of superinfection (black furry overgrowth on tongue, vaginal itching or discharge, loose or foul-smelling stools) and allergy.
Caution patient to notify health care professional if fever and diarrhea occur, especially if stool contains blood, pus, or mucus. Advise patient not to treat diarrhea without consulting health care professional. May occur up to several wk after discontinuation of medication.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆