Piperacillin is a broad-spectrum β-lactam antibiotic of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into Gram-negative bacteria and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen Pseudomonas aeruginosa. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin". 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 bacterias beta-lactamase.It was patented in 1974 and approved for medical use in 1981. Piperacillin is most commonly used in combination with the beta-lactamase inhibitor tazobactam (piperacillin/tazobactam), which enhances piperacillins effectiveness by inhibiting many beta lactamases to which it is susceptible. 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. The World Health Organization classifies piperacillin as critically important for human medicine. Medical uses
Piperacillin is used almost exclusively in combination with the beta lactamase inhibitor tazobactam for the treatment of serious, hospital-acquired infections. This combination is among the most widely used drug therapies in United States non-federal hospitals, accounting for $388M in spending in spite of being a low-cost generic drug.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.
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 ~10g every 24 hour dosing interval for continuous infusion.Organisms with a piperacillin-tazobactam MIC values equal to 32 or less than 16ml/I lead to 50% T>MIC when extended-interval intermittent administrations under two different dosing intervals (8.1g and 6.75g every 12 hours) were used against them. The pharmacodynamic target attainments corresponding to pathogens with MIC values of 16 mg/I are found to reach 92% when a more traditional 4 hour dosing regime is utilized to administer at irregular intervals. One study using the Monte Carlo simulation produced contradicting results to the previous studies, deducing that inadequate pharmacodynamic targets were achieved (T>MIC > 50%) for similar ESBL-producing bacteria, applying to both continuous and high dosage intermittent infusion. Chemistry

Derived from “the addition of a hydrophilic heterocyclic group to the α-amino group of ampicillin”, the structure consists of a thiazolidine ring conjoined to a β-lactam ring contained within several ring compounds. The addition of this substituent increases the compounds affinity to penicillin-binding protein PBP-3, improving activity against Gram-negative bacteria, and thus broadening its spectrum of activity. Susceptible β-lactamase producing bacteria such as Staphylococcus spp. or Haemophilus influenzae, the combination of tazobactam (which shares a similar structure to sulbactam, another β-lactamase inhibitor), and piperacillin significantly improves the stability of the drug against β-lactamases. == References ==