Tazobactam

This medicine combines two molecules with distinct roles. Piperacillin is a penicillin: it inhibits septum formation and cell wall synthesis in susceptible bacteria, which leads to their destruction. Tazobactam, on the other hand, has no antibacterial activity of its own. It protects piperacillin by neutralizing the enzymes that some bacteria produce to destroy it.

These enzymes, the beta-lactamases, cut the ring of the penicillin and inactivate it. Tazobactam binds to them and blocks them, in particular the class Bush 2b and 2b’ penicillinases and cephalosporinases, such as the enzymes of the TEM and SHV groups. By neutralizing them, it restores and broadens the action of piperacillin against bacteria that would otherwise resist it.

Piperacillin/tazobactam targets infections caused by beta-lactamase-producing bacteria, the very ones that tazobactam helps to bypass. Its spectrum notably covers Pseudomonas aeruginosa, a difficult pathogen often involved in severe infections. It is generally reserved for the hospital setting, for situations that call for a broad-spectrum antibiotic.

NICE recommends it as first-line treatment for bloodstream infections in neutropenic patients, whose immune defenses are weakened. In these people, an infection can progress quickly, and an antibiotic that is active from the outset makes a real difference. The prescription therefore depends on the type of bacteria targeted and on the fragility of the patient.

There is no oral form: piperacillin/tazobactam is given by the intravenous route only. The infusion usually lasts 30 minutes, sometimes 3 to 4 hours when a prolonged infusion is chosen. Since the medicine does not pass through the digestive tract, its administration does not depend on meals.

The half-life of each molecule is short, on the order of 0.7 to 1.2 hours in a healthy person. The product is therefore eliminated quickly, which calls for repeated administrations, every 6 to 8 hours depending on the regimen. Elimination is mainly through the kidney, where about 68% of the piperacillin and 80% of the tazobactam are found unchanged, hence a dose adjustment in cases of renal impairment. Treatment continues until the endpoint set by the care team, without stopping it on one’s own initiative.

In clinical trials, the most frequent effects mainly involve the digestive tract and the nervous system. Diarrhea comes first (11.3%), ahead of headache (7.7%), constipation (7.7%), nausea (6.9%) and insomnia (6.6%). These are followed by skin rash (4.2%), vomiting (3.3%) and fever (2.4%).

Like any broad-spectrum antibiotic, piperacillin/tazobactam can disrupt the gut flora and promote diarrhea linked to Clostridioides difficile. The picture ranges from mild diarrhea to severe colitis. Diarrhea that persists or worsens during or after treatment warrants medical advice.

The medicine provides a non-negligible amount of sodium: the label indicates, for example, 220 mg of sodium for a 2.25 g vial. In patients who must limit their salt intake, this load counts toward the daily total. It adds to the sodium from food and from other infusions.

Potassium, by contrast, may drop. Hypokalemia is possible, and the label recommends periodic electrolyte measurements in patients whose potassium reserves are already low, especially those on cytotoxic chemotherapy or on treatments that promote potassium loss. This parameter is checked with a blood test.

Several medicines interact with piperacillin/tazobactam. Probenecid prolongs the half-life of piperacillin by about 21% and that of tazobactam by about 71%, by blocking their secretion by the kidney. Piperacillin can inactivate aminoglycosides such as gentamicin and tobramycin by transforming them into inactive amides: the two must be given separately. It also reduces the renal clearance of methotrexate, which increases the risk of toxicity and calls for monitoring of its concentrations.

With vecuronium and other non-depolarizing neuromuscular blockers, it has been implicated in a prolongation of the neuromuscular block. When combined with high doses of heparin or with oral anticoagulants, coagulation parameters are checked more often. Laboratory monitoring includes electrolyte measurements, monitoring of renal function and, during prolonged treatments of at least 21 days, an assessment of hematopoietic function. Finally, piperacillin can give a false result on certain urine glucose tests based on copper reduction, producing a false positive: enzymatic glucose oxidase tests are then preferred.