When the T>MIC in the serum equates to 60 - 70% of the frequency for drug administration (dosing interval), maximal activity is achieved against Gram-negative bacteria, while for Gram-positive bacteria it occurs at around 40 - 50%.Within a 24-hour period in one clinical study, a T>MIC surpassing 60% was found for piperacillin-susceptible bacteria including Escherichia coli, Klebsiella pneumoniae and Staphylococcus aureus in two dosing regimes (4.5g every 8 hours and 3.375g every 8 hours).The evidence for this was obtained through Monte Carlo experiments procured by a special program (OPTAMA), where for several different scenarios (e.g. hospital acquired infections, secondary peritonitis, skin or soft tissue infections), the probability of attaining those figures were in the ranges of 85 - 95% and 90 - 89% respectively for the two regimes. In addition, two similar dosing regimes (3.375g and 4.5g every 6 hours) both had lower chances of reaching the 90% T>MIC threshold compared to the 50% threshold against hospital acquired pneumonia pathogens.The optimization of piperacillin-tazobactam drug efficiency has been covered by various studies, limiting the focus down to two types of infusions; continuous and intermittent. A comparison using the two administration methods under the same dosage regime of 13.5g per day highlighted no major differences when treating complex intra-abdominal infections. Furthermore, a follow-up analyzation of this trial deduced that both methods of administration lead to higher concentrations compared to the MIC of the pathogens that were used.
Adverse effects
Common side effects associated with the administration of piperacillin-tazobactam include:
Gastrointestinal: constipation, diarrhea, nausea, vomiting
Dermatologic: erythema, pain, phlebitis, rash
Neurologic: headaches, insomniaProlonged periods of piperacillin-tazobactam therapy have been associated with the potential development of hematologic adversities such as leukopenia (16.3%), neutropenia (10%), and eosinophilia (10%) in adult patients. The combination of piperacillin-tazobactam with other antibiotics was found to be a major risk factor for leukopenia as well. Additionally, the chances of developing these illnesses increases in younger patients with fewer conditions, prolonging their time to recover.Other cases of adverse effects include instances of renal dysfunction, hepatitis, hyperactivity, anemia, abnormalities in coagulation, and hypokalemia. Allergic reactions can be induced from the side chains of β-lactam antibiotics such as amoxicillin, or antibodies surrounding the nucleus of penicillin. Interactions
The combination of piperacillin and tazobactam, commonly branded as Zosyn, improves their overall bactericidal activity as amino-benzylpenicillins and ureidopencillins work synergistically with β-lactamase inhibitors. Concurrent use or unregulated dosages of piperacillin results in increasing levels of piperacillin within the body, prolonging neuromuscular transmission blockages created by non-depolarizing muscle relaxants, and disruptions in urine tests for glucose. Some compounds that may interfere with the bactericidal activity of piperacillin include chloramphenicol, macrolides, and sulfonamides. Following two studies conducted in 1986 and 2006, piperacillin was found to inhibit the removal of methotrexate in animal kidneys. Furthermore, in the presence of piperacillin-tazobactam, the decay time for methotrexate triples in comparison to the normal half-life, leaving the patient exposed to cytotoxic effects produced by the chemical agent.