Piperacillin / Tazobactam

ADMINISTRATION ROUTES:

IV

ALTERNATIVE NAMES:

Tazocin

ICU INDICATIONS:

1. Treatment of infections caused by susceptible organisms

2. Broad spectrum cover of hospital-acquired infections

PRESENTATION AND ADMINISTRATION:

IV:

4.5 gm vial of powder (4 gm piperacillin and 500 mg tazobactam)

Piperacillin / tazobactam must be administered as an initial bolus dose followed by an infusion.

The infusion must commence at half of the dosing interval. For example, if the desired dose is 4.5 gm QID (6 hourly), then 4.5 gm should be given as a bolus, followed 3 hours later by a continuous infusion of 9 gm running over 12 hours.

For the initial bolus dose:

Reconstitute with at least 20 ml of water for Injection and administer via slow IV injection over 3 - 5 minutes. Piperacillin / tazobactam is stable after reconstitution for 24 hours at room temperature.

For subsequent continuous infusions:

The dose to be administered over 12 hours should be added to 100 mL of compatible IV fluid for administration by infusion over 12 hours.

If the infusion is paused for less than 3 hours, the rate should be increased so it completes within 12 hours of when it was initially commenced. If necessary, any remaining antibiotic that has not been infused at the 12 hour mark can be administered as a bolus.

If the infusion is paused for 3 hours or more, a bolus dose should be administered, and the infusion should then restart at half of the dosing interval as previously described.

Compatible with the following IV fluids:

Normal saline, 5% glucose, sodium chloride

Store at room temperature

DOSAGE:

IV:

4.5 gm QID

First dose given as bolus

Subsequent doses given as infusions of 9 gm running for 12 hours

First infusion commences 3 hours after bolus dose

DOSAGE IN RENAL FAILURE AND RENAL REPLACEMENT THERAPY:

As above, piperacillin / tazobactam should be administered as an initial bolus dose, followed by an infusion commenced at half of the ongoing interval dosing.

Piperacillin / tazobactam is stable in solution for up to 24 hours, so the total daily dose required should be divided into two separate infusions, each given over 12 hours.

For any patient with a GFR ≤20 or receiving any form of renal replacment, the dose of piperacillin / tazobactam is 4.5 gm BD, or 9 gm total per day (see table below). This is given as two 12-hourly infusions. Each infusion contains 4.5 gm to achieve the daily total of 9 gm.

This should be administered thus:

1. Give a bolus dose of 4.5 gm as described above
2. Mix 4.5 gm of piperacillin / tazobactam with 20 mL of water for injection to reconstitute
3. Add this to 80 mL of compatible IV fluid for infusion (bringing the total for infusion to 100 mL)
4. Administer this dose by infusion, commencing 6 hours after the bolus dose (half of the interval dosing frequency) at 8.3 mL per hour (so it completes within 12 hours)
5. Repeat the 12 hourly infusion every 12 hours until the antibiotic course is stopped

Dose in renal impairment

Dose in renal replacement therapy

DOSAGE IN PAEDIATRICS:

IV:

50 - 75 mg/kg 6 - 8 hourly

CLINICAL PHARMACOLOGY:

Piperacillin / tazobactam has been shown to be active against most strains of the following microorganisms both in vitro and in clinical infections.

Aerobes, Gram-Positive:

• Staphylococcus aureus (excluding methicillin and oxacillin-resistant isolates)

Aerobes, Gram-Negative:

• Acinetobacter baumanii
• Escherichia coli
• Haemophilus influenzae (excluding beta-lactamase negative, ampicillin-resistant isolates)
• Klebsiella pneumoniae
• Pseudomonas aeruginosa (given in combination with an aminoglycoside to which the isolate is susceptible)

Anaerobes, Gram-Negative:

• Bacteroides fragilis group (B. fragilis, B. ovatus, B. thetaiotaomicron, and B. vulgatus)

The following in vitro data are available but their clinical significance is unknown. At least 90% of the following microorganisms exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for piperacillin / tazobactam. However, the safety and effectiveness of piperacillin / tazobactam in treating clinical infections due to these bacteria have not been established in adequate and well- controlled clinical trials.

Aerobes, Gram-Positive:

• Enterococcus faecalis (ampicillin or penicillin-susceptible isolates only)
• Staphylococcus epidermidis (excluding methicillin and oxacillin resistant isolates)
• Streptococcus agalactiae
• Streptococcus pneumoniae (penicillin-susceptible isolates only)
• Streptococcus pyogenes
• Viridans group streptococci

Aerobes, Gram-Negative:

• Citrobacter koseri
• Moraxella catarrhalis
• Morganella morganii
• Neisseria gonorrhoeae
• Proteus mirabilis
• Proteus vulgaris
• Serratia marcescens
• Providencia stuartii
• Providencia rettgeri
• Salmonella enterica

Anaerobes, Gram-Positive:

• Clostridium perfringens

Anaerobes, Gram-Negative:

• Bacteroides distasonis
• Prevotella melaninogenica

CONTRAINDICATIONS:

1. Hypersensitivity to piperacillin / tazobactam

WARNINGS:

Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients receiving therapy with beta-lactams. These reactions are more likely to occur in persons with a history of sensitivity to multiple allergens.

There have been reports of patients with a history of penicillin hypersensitivity who have experienced severe hypersensitivity reactions when treated with another beta-lactam. Before initiating therapy with tazocin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, other beta-lactams, and other allergens.

PRECAUTIONS:

General:

Bleeding manifestations have occurred in some patients receiving beta-lactam antibiotics, including piperacillin. These reactions have sometimes been associated with abnormalities of coagulation tests such as clotting time, platelet aggregation and prothrombin time, and are more likely to occur in patients with renal failure.

As with other penicillins, patients may experience neuromuscular excitability or convulsions if higher than recommended doses are given intravenously (particularly in the presence of renal failure).

Tazocin contains a total of 2.79 mEq (64 mg) of sodium per gram of piperacillin in the combination product. This should be considered when treating patients requiring restricted salt intake and in any patients with unexplained hypernatraemia.

Laboratory Tests:

No tests in addition to routine ICU tests are required.

Drug/Laboratory Test Interactions:

None noted

IMPORTANT DRUG INTERACTIONS IN ICU:

None of note

ADVERSE REACTIONS:

Body as a whole:

Fever, agitation, pain

Gastrointestinal:

Diarrhoea, nausea, vomiting, dyspepsia, constipation, stool changes, abdominal pain

CNS:

Insomnia, headache, anxiety, dizziness

Respiratory:

Rhinitis, dyspnoea

Cardiovascular:

Hypertension, chest pain, oedema