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Piperacillin is a broad-spectrum
β-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...
of the ureidopenicillin class. The chemical structure of piperacillin and other ureidopenicillins incorporates a polar side chain that enhances penetration into
Gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wall ...
and reduces susceptibility to cleavage by Gram-negative beta lactamase enzymes. These properties confer activity against the important hospital pathogen ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...
''. Thus piperacillin is sometimes referred to as an "anti-pseudomonal penicillin". When used alone, piperacillin lacks strong activity against the
Gram-positive In bacteriology, gram-positive bacteria are bacteria that give a positive result in the Gram stain test, which is traditionally used to quickly classify bacteria into two broad categories according to their type of cell wall. Gram-positive bact ...
pathogens such as '' Staphylococcus aureus'', as the beta-lactam ring is hydrolyzed by the bacteria's
beta-lactamase Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbap ...
. It was patented in 1974 and approved for medical use in 1981. Piperacillin is most commonly used in combination with the
beta-lactamase inhibitor Beta-lactamases, (β-lactamases) are enzymes () produced by bacteria that provide multi-resistance to beta-lactam antibiotics such as penicillins, cephalosporins, cephamycins, monobactams and carbapenems ( ertapenem), although carbapenems ...
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 Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
, 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 The National Institute for Health and Care Excellence (NICE) is an executive non-departmental public body of the Department of Health and Social Care in England that publishes guidelines in four areas: * the use of health technologies withi ...
as initial empiric treatment for people with suspected
neutropenic sepsis Febrile neutropenia is the development of fever, often with other signs of infection, in a patient with neutropenia, an abnormally low number of neutrophil granulocytes (a type of white blood cell) in the blood. The term neutropenic sepsis is also ...
. Piperacillin is used to treat patients diagnosed with various internal infections such as abdominal, bacteremia, gynecological,
respiratory The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
, and
urinary The urinary system, also known as the urinary tract or renal system, consists of the kidneys, ureters, bladder, and the urethra. The purpose of the urinary system is to eliminate waste from the body, regulate blood volume and blood pressure, co ...
, mainly caused by ''
Pseudomonas aeruginosa ''Pseudomonas aeruginosa'' is a common encapsulated, gram-negative, aerobic–facultatively anaerobic, rod-shaped bacterium that can cause disease in plants and animals, including humans. A species of considerable medical importance, ''P. aerug ...
'' 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 Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
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 and efficacy as other antibiotic combinations such as
ceftazidime Ceftazidime, sold under the brand name Fortaz among others, is a third-generation cephalosporin antibiotic useful for the treatment of a number of bacterial infections. Specifically it is used for joint infections, meningitis, pneumonia, sepsis, ...
with the aminoglycoside
tobramycin Tobramycin is an aminoglycoside antibiotic derived from '' Streptomyces tenebrarius'' that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of ''Pseudomonas ...
in the treatment of patients with hospital acquired pneumonia. In a clinical comparison primarily targeting patients not initially placed in intensive care units, piperacillin-tazobactam was found to produce higher clinical and microbiological rates of success. By contrast, the drug efficacy of ceftazidime and piperacillin-tazobactam resulted in similar response rates (61.5% and 63.9 respectively) when tobramycin was added into both groups. Identical evaluations are shown when compared to the
imipenem Imipenem (trade name Primaxin among others) is an intravenous β-lactam antibiotic discovered by Merck scientists Burton Christensen, William Leanza, and Kenneth Wildonger in the mid-1970s. Carbapenems are highly resistant to the β-lactamase enz ...
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.


Administration

Piperacillin is not absorbed orally, and must therefore be given by intravenous or intramuscular injection. It has been shown that the bactericidal actions of the drug do not increase with concentrations of piperacillin higher than 4-6 x MIC, which means that the drug is concentration-independent in terms of its actions. Piperacillin has instead shown to offer higher bactericidal activity when its concentration remains above the MIC for longer periods of time (50% time>MIC showing the highest activity). 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. 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. The studies supporting this theory generally administered ~3.375g of piperacillin-tazobactam every 8 hours during a 4-hour infusion, while for organisms with higher minimum inhibitory concentrations, ~4.5g of piperacillin-tazobactam was administered every 6 hours during a 3-hour infusion. The recommended doses provided by the BNFC for infants with hospital-acquired infections are 90 mg/kg every 8 hours for infants, a maximum of 4.5g every 6 hours for children, and 4.5g every 8 hours for children aged 12 and above. A dosage of 90 mg/kg every 6 hours is suggested for infants and children diagnosed with neutropenia.


Adverse effects

Common side effects associated with the administration of piperacillin-tazobactam include: * Gastrointestinal: constipation, diarrhea, nausea, vomiting * Dermatologic:
erythema Erythema (from the Greek , meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not asso ...
, pain,
phlebitis Phlebitis (or Venitis) is inflammation of a vein, usually in the legs. It most commonly occurs in superficial veins. Phlebitis often occurs in conjunction with thrombosis and is then called thrombophlebitis or superficial thrombophlebitis. Unlike ...
, rash * Neurologic: headaches,
insomnia Insomnia, also known as sleeplessness, is a sleep disorder in which people have trouble sleeping. They may have difficulty falling asleep, or staying asleep as long as desired. Insomnia is typically followed by daytime sleepiness, low energy, ...
Prolonged periods of piperacillin-tazobactam therapy have been associated with the potential development of hematologic adversities such as
leukopenia Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of in ...
(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 Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes ( jaundice), poor appetite, vomiting, tiredness, abdominal ...
, hyperactivity,
anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...
, abnormalities in coagulation, and
hypokalemia Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an abno ...
. Allergic reactions can be induced from the side chains of
β-lactam antibiotic β-lactam antibiotics (beta-lactam antibiotics) are antibiotics that contain a beta-lactam ring in their chemical structure. This includes penicillin derivatives (penams), cephalosporins and cephamycins (cephems), monobactams, carbapenems and ...
s such as
amoxicillin Amoxicillin is an antibiotic medication used to treat a number of bacterial infections. These include middle ear infection, strep throat, pneumonia, skin infections, and urinary tract infections among others. It is taken by mouth, or less c ...
, 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,
macrolide The Macrolides are a class of natural products that consist of a large macrocyclic lactone ring to which one or more deoxy sugars, usually cladinose and desosamine, may be attached. The lactone rings are usually 14-, 15-, or 16-membered. Ma ...
s, 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. While penicillin antibiotics generally work synergistically with
aminoglycoside Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside (sugar). The term can also refer ...
s by enhancing their penetration of bacterial membranes, they can also work adversely by inactivating them. A reformulation of
ethylenediaminetetraacetic acid Ethylenediaminetetraacetic acid (EDTA) is an aminopolycarboxylic acid with the formula H2N(CH2CO2H)2sub>2. This white, water-soluble solid is widely used to bind to iron (Fe2+/Fe3+) and calcium ions (Ca2+), forming water-soluble complexes ev ...
and piperacillin-tazobactam has produced results showing an increase in their affinity with
amikacin Amikacin is an antibiotic medication used for a number of bacterial infections. This includes joint infections, intra-abdominal infections, meningitis, pneumonia, sepsis, and urinary tract infections. It is also used for the treatment of mu ...
and gentamicin in vitro, enabling the process of simultaneous Y-site infusion to occur. However,
tobramycin Tobramycin is an aminoglycoside antibiotic derived from '' Streptomyces tenebrarius'' that is used to treat various types of bacterial infections, particularly Gram-negative infections. It is especially effective against species of ''Pseudomonas ...
was found to be incompatible as a combination through Y-site infusion.


Pharmacology

Piperacillin irreversibly binds to the enzyme penicillin-binding proteins, inhibiting the biosynthesis of bacterial cell walls.


Mechanism of action

As a β-lactam antibiotic, piperacillin inhibits penicillin-binding proteins, preventing the spread of bacteria and infections. Responsible for catalyzing the cross-linkage between
peptidoglycan Peptidoglycan or murein is a unique large macromolecule, a polysaccharide, consisting of sugars and amino acids that forms a mesh-like peptidoglycan layer outside the plasma membrane, the rigid cell wall (murein sacculus) characteristic of most ba ...
strands that protect the bacterial cell from osmotic rupture, penicillin-binding proteins are unique to bacterial organisms, where every known bacteria with a peptidoglycan cell wall consists of homologous sub-families. By sharing a similar stereochemistry with the substrates that bind to penicillin-binding proteins, piperacillin is able to bind to serine residues found at the active site of the enzyme through the formation of a covalent complex, preventing other substrates from binding. Moreover, this leads to the release of
autolysin Autolysins are endogenous lytic enzymes that break down the peptidoglycan components of biological cells which enables the separation of daughter cells following cell division. They are involved in cell growth, cell wall metabolism, cell division a ...
s that break down the bacteria's cell wall. Some β-lactamase enzymes also consist of residue at their active site, enabling them to hydrolyze the β-lactam ring found within these antibiotics. However, this hydrolytic activity is inhibited when piperacillin works in conjunction with tazobactam. Tazobactam binds to these enzymes to form a stable acyl-enzyme complex; similar to one formed during the hydrolysis of the β-lactam ring. Thus, protecting piperacillin from
hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution, elimination, and solvation reactions in which water is the nucleophile. Biological hydrolys ...
. The inclusion of a β-lactamase inhibitor does not always increase drug efficacy. Some bacteria may produce certain types of β-lactamase such as AmpC, which are intrinsically resistant to tazobactam.


Mechanisms of resistance

A major mechanism of resistance against piperacillin-tazobactam is Gram-negative bacteria producing β-lactamases. Other currently known mechanisms include mutations in the active site of penicillin-binding proteins, changes in membrane efflux, or bacteria permeability. Some enzymes, such as extended-spectrum β-lactamase (ESBL) have evolved from narrow-spectrum β-lactamases due to genetic mutations, increasing their capabilities to hydrolyze much broader spectrum penicillin. Due to prior conflicting reports on the drug's affinity with ESBL-producing bacteria, piperacillin-tazobactam treatment for such is not recommended. Antibiotic resistance occurs sporadically, conferred by the continuous use of piperacillin-tazobactam in situations where it may prove to be ineffective, leading to cases where plasmid-mediated β-lactamases are being produced in bacteria that do not naturally produce it. Some Gram-positive bacteria penicillin-binding proteins such as '' Enterococcus faecium'' (PBP-5) or '' Staphylococcus aureus'' (PBP-2a) are intrinsically antibiotic resistant, consisting of relatively low affinity with piperacillin and therefore high resistance to piperacillin-tazobactam. Furthermore, mutations in penicillin-binding proteins cause fluctuations in piperacillin affinity, whereas ''Streptococcus pneumoniae'' (PBP-2b) autolytic response is significantly reduced due to decreased affinity with piperacillin. Although membrane permeability changes are less common as a mechanism of resistance, studies investigating
Klebsiella pneumoniae ''Klebsiella pneumoniae'' is a Gram-negative, non-motile, encapsulated, lactose- fermenting, facultative anaerobic, rod-shaped bacterium. It appears as a mucoid lactose fermenter on MacConkey agar. Although found in the normal flora of the mo ...
have reported a correlation between decreased permeability of piperacillin and increased SHV-1 β-lactamase production.


Pharmacokinetics

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. As the gastrointestinal tract does not absorb piperacillin and tazobactam, they are dissolved in a solution before being administered to a patient, through parenteral means. Excreted through renal mechanisms like glomerular or tubular filtration as a component of urine, uncontrolled dosages of the drug can cause renal dysfunction and competitive inhibition of excretion, delaying piperacillin-tazobactam excretion, and endangering patients to drug exposure. Although the distribution of the drug remained the same, the half-life for elimination increased by three to five folds for patients diagnosed with renal dysfunction. Measured by
creatinine clearance Assessment of kidney function occurs in different ways, using the presence of symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging. Functions of a healthy kidney include maintaining a person's fluid ...
(CrCl), patients with less than 30ml/min of clearance had significantly reduced levels of piperacillin/tazobactam excretion, measuring down to 35% of the initial dosage, while the area under the curve (AUC) for piperacillin increased by about three folds for those with less than 20ml/min. A reduced dosage or alteration in the interval of administration is recommended for patients lying under 40ml/min of CrCl, depending on the severity of dysfunction. Renal is the main pathway for drug elimination for both tazobactam and piperacillin in the body. While there are other non-renal means of drug elimination like Hepatobiliary excretion, they occur less frequently. A substantial amount (~80%) of piperacillin found in urine when excreted through glomerular and tubular filtration is unmetabolized. Tazobactam renal elimination may be significantly reduced through piperacillin interaction, dropping from 63.7% to 56.8% of the administered dose over a 24-hour period. Piperacillin may be actively diffused through filtration into the biliary tract during renal clearing, indicated by a generally higher concentration of piperacillin than tazobactam in the bile. 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. Due to the hydrophilic nature of piperacillin-tazobactam, a volume distribution of ~15 L amounting to various sites (tissues) is desired, as hydrophilic compounds are not able to pass through plasma membranes as easily as hydrophobic compounds. Concentrations often in the range of 90 MIC or above are located in specific areas including the gallbladder, lung, muscle, and skin, making up 16 - 85% of the plasma concentrations. The concentration of piperacillin-tazobactam is especially lower in fatty tissue, making up less than 10% of the plasma concentrations.


Pharmacodynamics

Compared to concentration dependent bactericidal antibiotics like aminoglycosides and
fluoroquinolones A quinolone antibiotic is a member of a large group of broad-spectrum bacteriocidals that share a bicyclic core structure related to the substance 4-quinolone. They are used in human and veterinary medicine to treat bacterial infections, as we ...
, the antibacterial activity of β-lactam antibiotics are generally more time dependent. Unlike the former, when piperacillin-tazobactam concentrations exceed
minimum inhibitory concentration In microbiology, the minimum inhibitory concentration (MIC) is the lowest concentration of a chemical, usually a drug, which prevents visible growth of a bacterium or bacteria. MIC depends on the microorganism, the affected human being (in vivo only ...
s (MIC) of a pathogen by five folds, the exponential relationship between concentration and activity begins to level off. Otherwise, piperacillin-tazobactam bactericidal efficacy is shown to consist of a strong association with the duration of time the concentration exceeds minimum inhibitory concentrations (T>MIC). 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 ''Escherichia coli'' (),Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. also known as ''E. coli'' (), is a Gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Esc ...
'', ''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 Monte Carlo (; ; french: Monte-Carlo , or colloquially ''Monte-Carl'' ; lij, Munte Carlu ; ) is officially an administrative area of the Principality of Monaco, specifically the ward of Monte Carlo/Spélugues, where the Monte Carlo Casino is ...
experiments procured by a special program (OPTAMA), where for several different scenarios (e.g. hospital acquired infections, secondary
peritonitis Peritonitis is inflammation of the localized or generalized peritoneum, the lining of the inner wall of the abdomen and cover of the abdominal organs. Symptoms may include severe pain, swelling of the abdomen, fever, or weight loss. One part o ...
, 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. Similar results are found in a study where a select number of β-lactam susceptible pathogens consisting of ''
Enterococcus faecalis ''Enterococcus faecalis'' – formerly classified as part of the group D ''Streptococcus'' system – is a Gram-positive, commensal bacterium inhabiting the gastrointestinal tracts of humans. Like other species in the genus ''Enterococcus'', ''E ...
'', ''Klebsiella pneumoniae'' and ''
Citrobacter freundii ''Citrobacter freundii'' is a species of facultative anaerobic Gram-negative bacteria of the family Enterobacteriaceae which currently consists of 13 recognized species. These bacteria have a rod shape with a typical length of 1–5 μm. Most ''C ...
'' 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 Ampicillin is an antibiotic used to prevent and treat a number of bacterial infections, such as respiratory tract infections, urinary tract infections, meningitis, salmonellosis, and endocarditis. It may also be used to prevent group B stre ...
”, 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 compound's 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 ''Haemophilus influenzae'' (formerly called Pfeiffer's bacillus or ''Bacillus influenzae'') is a Gram-negative, non-motile, coccobacillary, facultatively anaerobic, capnophilic pathogenic bacterium of the family Pasteurellaceae. The bacter ...
'', the combination of tazobactam (which shares a similar structure to
sulbactam Sulbactam is a β-lactamase inhibitor. This drug is given in combination with β-lactam antibiotics to inhibit β-lactamase, an enzyme produced by bacteria that destroys the antibiotics. It was patented in 1977 and approved for medical use in ...
, another β-lactamase inhibitor), and piperacillin significantly improves the stability of the drug against β-lactamases.


References

{{PenicillinAntiBiotics Penicillins Enantiopure drugs Wyeth brands Diketopiperazines Phenyl compounds Carboxylic acids Acetamides