Piperacillin, a broad spectrum, semi-synthetic penicillin active against many gram-positive and gram-negative aerobic and anaerobic bacteria, exerts bactericidal activity by inhibition of both septum and cell wall synthesis. Tazobactam is a potent inhibitor of many beta-lactamases, including the plasmid and chromosomally mediated enzymes that commonly cause resistance to penicillins. Tazobactam enhances and extends the antibiotic spectrum of Piperacillin to include many beta-lactamase-producing bacteria normally resistant to it. Thus, this infusion combines the properties of a broad-spectrum antibiotic and a beta-lactamase inhibitor.

Piperacillin and tazobactam is a combination product consisting of a penicillin-class antibacterial, piperacillin, and a β-lactamase inhibitor, tazobactam, indicated for the treatment of patients with moderate to severe infections caused by susceptible isolates of the designated bacteria in the conditions listed below.

Intra-abdominal Infections: Appendicitis (complicated by rupture or abscess) and peritonitis caused by β-lactamase producing isolates of Escherichia coli or the following members of the Bacteroides fragilis group: B. fragilis, B. ovatus, B. thetaiotaomicron, or B. vulgatus.

Skin and Skin Structure Infections: Uncomplicated and complicated skin and skin structure infections, including Cellulites, cutaneous abscesses and ischemic/diabetic foot infections caused by β-lactamase producing isolates of Staphylococcus aureus.

Female Pelvic Infections: Postpartum endometritis or pelvic inflammatory disease caused by β-lactamase producing isolates of Escherichia coli.

Community-acquired pneumonia: Community-acquired pneumonia (moderate severity only) caused by β lactamase producing isolates of Haemophilus influenzae.

Nosocomial pneumonia: Nosocomial pneumonia (moderate to severe) caused by β-lactamase producing isolates of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumanii, Haemophilus influenzae, Klebsiella pneumoniae, and Pseudomonas aeruginosa (Nosocomial pneumonia caused by P. aeruginosa should be treated in combination with an aminoglycoside).

Piperacillin and tazobactam should be administered by intravenous infusion over 30 minutes.

Adult Patients: The usual total daily dose of Piperacillin and tazobactam for adults is 3.375 g every six hours totaling 13.5 g (12.0 g piperacillin/1.5 g tazobactam). The usual duration of treatment is from 7 to 10 days.

Nosocomial Pneumonia: Initial presumptive treatment of patients with nosocomial pneumonia should start with piperacillin and tazobactam at a dosage of 4.5 g every six hours plus an aminoglycoside, totaling 18.0 g (16.0 g piperacillin/2.0 g tazobactam). The recommended duration of the treatment for nosocomial pneumonia is 7 to 14 days. Treatment with the aminoglycoside should be continued in patients from whom Pseudomonas aeroginosa is isolated.

Pediatric Patients: For children with appendicitis and/or peritonitis 9 months of age or older, weighing up to 40 kg, and with normal renal function, the recommended piperacillin and tazobactam dosage is 100 mg piperacillin/12.5 mg tazobactam per kilogram of body weight, every 8 hours. For pediatric patients between 2 months and 9 months of age, the recommended dosage based on Pharmacokinetic modeling, is 80 mg piperacillin/10 mg tazobactam per kilogram of body weight, every 8 hours. Pediatric patients weighing over 40 kg and with normal renal function should receive the adult dose. It has not been determined how to adjust piperacillin and tazobactam dosage in pediatric patients with renal impairment.

Piperacillin and tazobactam is contraindicated in patients with a history of allergic reactions to any of the penicillins, cephalosporins, or β -lactamase inhibitors.

Adverse events primarily involving the skin, including rash, pruritus and Purpura; the gastrointestinal system including diarrhea, Constipation, nausea, vomiting, Dyspepsia and Abdominal Pain; General disorders and administration site conditions including Fever, Injection site reaction (≤1%) and Rigors. (≤1%), Immune hypersensitivity reactions, anaphylactic/anaphylactoid reactions (including shock) (≤1%), Infections-Candidiasis and Pseudomembranous colitis (≤1%), Metabolism and nutrition disorders- Hypoglycemia (≤1%), Musculoskeletal and connective tissue disorders- Myalgia and Arthralgia (≤1%), Psychiatric disorders Insomnia, Vascular disorders- Phlebitis Thrombophlebitis(≤1%), Hypotension(≤1%), Flushing(≤1%), Respiratory, thoracic and mediastinal disorders- Epistaxis (≤1%).

Overdose Effects

There have been post marketing reports of overdose with piperacillin/tazobactam. The majority of those events experienced, including nausea, vomiting, and diarrhea, have also been reported with the usual recommended dosages. Patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure). Treatment should be supportive and symptomatic according the patient's clinical presentation.

Serious hypersensitivity reactions (anaphylactic/anaphylactoid) reactions have been reported in patients receiving Piperacillin and tazobactam. Discontinue Piperacillin and tazobactam if a reaction occurs.

Piperacillin and tazobactam may cause severe cutaneous adverse reactions, such as Stevens- Johnson syndrome, toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms, and acute generalized exanthematous pustulosis. Discontinue Piperacillin and tazobactam for progressive rashes.

Hematological effects (including bleeding, leukopenia and neutropenia) have occurred. Monitor hematologic tests during prolonged therapy.

Nephrotoxicity in critically ill patients has been observed; the use of Piperacillin and tazobactam 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. 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.

Clostridium difficile associated diarrhea: Evaluate patients if diarrhea occurs.

Use in Special Populations

Pediatric Use: Use of Piperacillin and tazobactam in pediatric patients 2 months of age or older with appendicitis and/or peritonitis is supported by evidence from well-controlled studies and pharmacokinetic studies in adults and in pediatric patients. It has not been determined how to adjust Piperacillin and tazobactam dosage in pediatric patients with renal impairment.

Geriatric Use: Patients over 65 years are not at an increased risk of developing adverse effects solely because of age. However, dosage should be adjusted in the presence of renal impairment. This may be clinically important with regard to such diseases as congestive heart failure.

Renal Impairment: In patients with creatinine clearance ≤40 mL/min and dialysis patients (hemodialysis and CAPD), the intravenous dose of Piperacillin and tazobactam should be reduced to the degree of renal function impairment.

Hepatic Impairment: Dosage adjustment of Piperacillin and tazobactam is not warranted in patients with hepatic cirrhosis.

Patients with Cystic Fibrosis: As with other semisynthetic penicillins, piperacillin therapy has been associated with an increased incidence of fever and rash in cystic fibrosis patients

Pregnancy & Lactation

Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data with piperacillin and/or tazobactam in pregnant women to inform a drug-associated risk for major birth defects and miscarriage. Piperacillin is excreted in human milk; tazobactam concentrations in human milk have not been studied. No information is available on the effects of piperacillin and tazobactam on the breastfed child or on milk production.