When used alone, piperacillin lacks strong activity against the Gram-positive pathogens such as Staphylococcus aureus, as the beta-lactam ring is hydrolyzed by the bacteria's beta-lactamase.

However, the co-administration of tazobactam does not confer activity against MRSA, as penicillin (and most other beta lactams) do not avidly bind to the penicillin-binding proteins of this pathogen.

[6] Piperacillin-tazobactam is recommended as part of a three-drug regimen for the treatment of hospital-acquired pneumonia suspected as being due to infection by multi-drug resistant pathogens.

[8] Piperacillin-tazobactam is recommended by the National Institute for Health and Care Excellence as initial empiric treatment for people with suspected neutropenic sepsis.

[9] Piperacillin is used to treat patients diagnosed with various internal infections such as abdominal, bacteremia, gynecological, respiratory, and urinary, mainly caused by Pseudomonas aeruginosa and other infectious bacteria.

[13] The combination of piperacillin and an aminoglycoside is commonly used to treat severe infections, but due to the incompatibilities in drug interaction, they are administered separately.

[16] Identical evaluations are shown when compared to the imipenem and tobramycin combination, where the administration of piperacillin-tazobactam on patients (especially those under mechanical ventilation) was only consisted of a slightly higher response rate.

This higher activity present in continuous dosing has not been directly linked to clinical outcomes, but however does show promise of lowering possibility of resistance and decreasing mortality.

[19] Extending the time of piperacillin-tazobactam infusion allows the drugs to maintain the necessary concentrations needed within the body to prevent bacterial growth, enhancing bactericidal activity.

[23] Other cases of adverse effects include instances of renal dysfunction, hepatitis, hyperactivity, anemia, abnormalities in coagulation, and hypokalemia.

[24] 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.

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.

[22] A reformulation of ethylenediaminetetraacetic acid and piperacillin-tazobactam has produced results showing an increase in their affinity with amikacin and gentamicin in vitro, enabling the process of simultaneous Y-site infusion to occur.

[29] Some β-lactamase enzymes also consist of residue at their active site, enabling them to hydrolyze the β-lactam ring found within these antibiotics.

[35][36] Piperacillin is generally available in their stable form as crystallized potassium or sodium salt, quickly losing bactericidal activity upon dissolution due to their short half-lives.

[41] The metabolites that make up the remaining percentage in the excreted urine are composed of M1 (inactive) and N-desethyl-piperacillin (active), formed from the division of β-lactam rings of both tazobactam and piperacillin respectively.

[47][53] A comparison using the two administration methods under the same dosage regime of 13.5 g per day highlighted no major differences when treating complex intra-abdominal infections.

[54] Similar results are found in a study where a select number of β-lactam susceptible pathogens consisting of Enterococcus faecalis, Klebsiella pneumoniae and Citrobacter freundii were used to test a ~10 g every 24 hour dosing interval for continuous infusion.

[53] The pharmacodynamic target attainments corresponding to pathogens with MIC values of 16 μg/mL are found to reach 92% when a more traditional 4 hour dosing regime is utilized to administer at irregular intervals.