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Piperacillin/Tazobactam: Mechanism of Action, Side Effects and Dosage

Piperacillin is a broad-spectrum penicillin for parenteral antibiotic therapy, which, in combination with the β-lactamase inhibitor tazobactam, has a broad antibiotic spectrum against gram-negative and gram-positive bacteria.

Mechanism of Action:

Piperacillin inhibits the peptidoglycan synthesis of the bacterial wall: it binds to so-called penicillin-binding proteins (peptidoglycan synthetases) and inhibits the polymerization of the peptidoglycan and covalent cross-linking of the bacterial wall (β-lactame antibiotics). Tazobactam has a small antibiotic activity; it inhibits the β-lactamase of many bacteria and prevents the inactivation of piperacillin.

Antibiotic Spectrum of Piperacillin/Tazobactam:

Streptococci, pneumococci, Enterococcus faecalis, oxacillin-sensitive staphylococci, Haemophilus influenzae, E. coli, Seratia, Proteus, Klebsiella, Pseudomonas and anaerobes (Bacteroides, Fusobacterium, etc.). Unreliable or insufficient effect on atypical bacteria (chlamydia, mycoplasma), Clostridium difficile, oxacillin-resistant staphylococci (MRSA), and Enterococcus faecium.

Urological Indications for Piperacillin/Tazobactam:

Parenteral therapy of severe complicated urinary tract infections (pyelonephritis, catheter-associated infections, prostatitis, epididymitis) in adults and children. Due to its broad antibiotic spectrum, piperacillin/tazobactam is suitable for the calculated initial therapy of severe infections or urosepsis before identification of the responsible pathogen.

Pharmacokinetics of Piperacillin/Tazobactam:

• Only intravenous administration is possible. Both compounds have a half-life of 1 hour and a protein binding of 30%. 
• Piperacillin and tazobactam are only slightly metabolized, with 60–80% unchanged renal elimination.

Side Effects of Piperacillin/Tazobactam:

• Common (over 1%): gastrointestinal side effects (diarrhea, nausea), exanthema, increased liver enzymes, and phlebitis.
• Rare but potentially serious side effects are pseudomembranous enterocolitis, seizures, severe cutaneous skin reactions, anaphylaxis, cholestatic jaundice, hemolytic anemia, and thrombocytopenia.

Drug Interactions:

Probenicid inhibits renal tubular excretion and increases the serum concentration of piperacillin/tazobactam.

Contraindications:

Penicillin allergy.

Dosage of Piperacillin/Tazobactam:

• Adults: 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 hours i.v., in particularly severe infections, the dose can be administered every six hours.
• Children older than 2 years receive 100/12.5 mg piperacillin/tazobactam per kgBW i.v. every 8 hours, up to a maximum of 4.5 g.
• In case of renal insufficiency (GFR below 40 ml/min), the maximum dosage is 4.5 g every 8 hours, and below 20 ml/min, it is 4.5 g every 12 hours.

References

Simon und Stille 1997 SIMON, C. ; STILLE, W.: Antibiotika-Therapie in Klinik und Praxis.
9. Auflage.
Stuttgart New York : Schattauer, 1997

  Deutsche Version: Pharmakologie und Nebenwirkungen von Piperacillin/Tazobactam

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