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 bacteria's 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 piperacillin's 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. It is also one of several antibacterial drugs recommended for the treatment of infections known to be caused by anaerobic Gram-negative rods. Piperacillin-tazobactam is recommended by the National Institute for Health and Care Excellence as initial empiric treatment for people with suspected neutropenic sepsis. 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. They are primarily used in current and former neutropenic patients, and patients with biliary tract infections. Other uses include applications in surgical infection prophylaxis; in biliary surgery, a single dose of piperacillin is administered intravenously to inhibit the development of acute cholangitis and prevent wound infections. 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. Pneumonia The piperacillin-tazobactam (piptaz) antibiotic commonly used with an aminoglycoside retains similar levels of drug safety