Piperacillin
🧬 Cross-allergy: Penicillins
JFDA label: Prizma
Mechanism of Action
Inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Indications
Approved
- Infection
Antimicrobial Spectrum
Expected / intrinsic spectrum (EUCAST breakpoints & labels) — not local resistance. Source: EUCAST v16 · curated · openfda-label.
Bacteria
| Organism | Activity | MIC |
|---|---|---|
| Acinetobacter baumannii | Active | — |
| Anaerobes | Susceptible | 24.0 mg/L |
| Bacteroides distasonis | Active | — |
| Bacteroides fragilis | Active | — |
| Bacteroides thetaiotaomicron | Active | — |
| Citrobacter koseri | Active | — |
| Clostridium difficile | Active | — |
| Clostridium perfringens | Active | — |
| Enterobacter cloacae | Susceptible | 8.0 mg/L |
| Enterobacterales | Susceptible | 8.0 mg/L |
| Enterococcus faecalis | Active | — |
| Enterococcus spp. | Susceptible | 0.0015 mg/L |
| Escherichia coli | Susceptible | 8.0 mg/L |
| Haemophilus influenzae | Susceptible | 0.257 mg/L |
| Klebsiella pneumoniae | Susceptible | 8.0 mg/L |
| Moraxella catarrhalis | Susceptible | -1.0 mg/L |
| Morganella morganii | Active | — |
| Neisseria gonorrhoeae | Active | — |
| Prevotella melaninogenica | Active | — |
| Proteus mirabilis | Active | — |
| Proteus vulgaris | Active | — |
| Providencia rettgeri | Active | — |
| Providencia stuartii | Active | — |
| Pseudomonas aeruginosa | Susceptible | 16.0 mg/L |
| Pseudomonas aeruginosa | Susceptible | 0.001 mg/L |
| Salmonella enterica | Active | — |
| Serratia marcescens | Active | — |
| Staphylococcus aureus | Active | — |
| Staphylococcus epidermidis | Active | — |
| Streptococcus agalactiae | Active | — |
| Streptococcus pneumoniae | Active | — |
| Streptococcus pyogenes | Active | — |
| Vibrio spp. | Susceptible | 11.0 mg/L |
| Pseudomonas aeruginosa | Resistant | 16.0 mg/L |
Class profile
| gramStatus | Both |
|---|---|
| spectrumBreadth | Extended |
| atypicalCoverage | No |
| isBactericidal | 1 |
| moaCategory | Cell wall synthesis inhibitor (beta-lactam, anti-pseudomonal penicillin) |
| pdIndex | Time-dependent |
| postAntibioticEffect | None |
| mrsaCoverage | 0 |
| resistanceMechanisms | Beta-lactamase production (AmpC),Reduced outer membrane permeability (OprD loss),Efflux pumps (MexAB-OprM) |
Contraindications
Source: Lexicomp
- Hypersensitivity to any of the penicillins and/or cephalosporins or any component of the formulation Absolute
- hypersensitivity to local anesthetics of the amide type (when reconstituted with lidocaine for IM use) Absolute
Adverse Reactions
Cardiac disorders (1)
Not Known Local thrombophlebitis
Nervous system disorders (4)
Not Known Confusion · drowsiness · myoclonus · seizure
Renal and urinary disorders (2)
Not Known Acute interstitial nephritis · acute renal failure
Blood and lymphatic system disorders (6)
Not Known Abnormal platelet aggregation (high doses) · agranulocytosis · hemolytic anemia · pancytopenia · positive direct Coombs test · prolonged prothrombin time (high doses)
Immune system disorders (3)
Not Known Anaphylaxis · hypersensitivity reaction · Jarisch-Herxheimer reaction
Metabolism and nutrition disorders (2)
Not Known Electrolyte disturbance · hypokalemia
Skin and subcutaneous tissue disorders (3)
Not Known Skin rash · toxic epidermal necrolysis · urticaria
General disorders and administration site conditions (1)
Not Known Fever
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Anaphylactoid/hypersensitivity reactions
Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous IgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Discontinue if hypersensitivity occurs; initiate appropriate rescue treatment for serious hypersensitivity reactions.
Bleeding disorders
Particularly in patients with renal impairment, bleeding disorders have been observed; discontinue if thrombocytopenia or bleeding occurs.
Leukopenia/neutropenia
During prolonged use, leukopenia and neutropenia have been reported.
Superinfection
Prolonged use may result in fungal or bacterial superinfection, including C. difficile-associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment. Disease-related concerns:
Cardiovascular disease
Use with caution particularly in sodium-restricted patients receiving prolonged therapy; formulation contains 42.5 mg of sodium per gram. Monitor electrolyte status and cardiac function with prolonged therapy.
Cystic fibrosis
An increased frequency of fever and rash has been reported in patients with cystic fibrosis.
Infectious mononucleosis
Patients with infectious mononucleosis have developed rash during therapy with other penicillins (eg, ampicillin, amoxicillin).
Renal impairment
Use with caution in patients with renal impairment, due to sodium load and adverse effects (hematologic, neuropsychological changes); dosage adjustment recommended.
Seizure disorders
High drug levels, particularly in the presence of renal impairment, may increase risk of seizures. Use with caution in patients with a history of seizure disorder.
Syphilis
Symptoms of syphilis may be masked or delayed in patients receiving high-dose antimicrobial treatment of gonorrhea; patients with gonorrhea should be evaluated for syphilis prior to initiating antimicrobial treatment and if syphilis is suspected, continue serologic testing monthly for at least 4 months.
Pregnancy & Lactation
Pregnancy
Adverse events have not been observed in animal reproduction studies. Piperacillin crosses the placenta and distributes into the amniotic fluid (Brown, 1990; Heikkilä, 1991). Due to pregnancy-induced physiologic changes, some pharmacokinetic parameters of piperacillin may be altered. At term, the apparent volume of distribution of piperacillin is increased and peak concentrations are significantly lower. Total clearance is normal to increased at term (Heikkilä, 1991; Voight, 1985). These changes continue into the early postpartum period (Charles, 1985; Martens, 1987).
Lactation
Small amounts of piperacillin are excreted in breast milk. The manufacturer recommends that caution be exercised when administering piperacillin to nursing women. Nondose-related effects could include modification of bowel flora.
Monitoring
| Efficacy | Culture and susceptibility testing; clinical resolution (temperature, WBC, CRP, procalcitonin) |
|---|---|
| Toxicity | Renal function (dose adjustment in renal impairment); hepatic function for hepatically cleared agents; signs of C. difficile infection (diarrhoea) |
| Clinical pearl | Culture results guide de-escalation to narrower-spectrum therapy. Review antibiotic appropriateness at 48–72 h (antimicrobial stewardship). |
| Counseling | Complete the full course. Report persistent diarrhoea, rash, or lack of improvement after 48–72 h. |
Chemistry & Properties
| Formula | C23H27N5O7S |
|---|---|
| Molecular weight | 517.56 g/mol |
| IUPAC name | (2S,5R,6R)-6-[[(2R)-2-[(4-ethyl-2,3-dioxopiperazine-1-carbonyl)amino]-2-phenylacetyl]amino]-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid |
| CAS | 61477-96-1 |
| PubChem CID | 43672 |
| InChIKey | IVBHGBMCVLDMKU-GXNBUGAJSA-N |
| logP | -0.24 (XLogP 0.5) |
| Polar surface area | 156.43 Ų |
| H-bond acceptors / donors | 7 / 3 |
| Drug-likeness (QED) | 0.34 |
| Lipinski violations | 1 |
SMILES
CCN1CCN(C(=O)N[C@@H](C(=O)N[C@@H]2C(=O)N3[C@@H]2SC(C)(C)[C@@H]3C(=O)O)c2ccccc2)C(=O)C1=OBiology & Pharmacokinetics
Pharmacokinetics predicted
| Bioavailability | 70.0% |
|---|---|
| Half-life | 1.056 h |
| Volume of distribution | 0.273 L/kg |
| Protein binding | 39.3% |
| BBB penetrant | No |
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP2C19 | Substrate | — |
Transporters
BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)OAT1 (Inhibitor)OAT3 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)P-gp (Inhibitor)PEPT1 (Inhibitor)P-gp (Substrate)PEPT1 (Substrate)
Drug–drug interactions (24, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Methotrexate | major | |
| Vancomycin | major | |
| Amikacin | moderate | |
| Amikacin (liposome) | moderate | |
| Chloramphenicol | moderate | |
| Demeclocycline | moderate | |
| Dicoumarol | moderate | |
| Doxycycline | moderate | |
| Ethinylestradiol | moderate | |
| Gentamicin | moderate | |
| Iodide I-123 | moderate | |
| Iodide I-131 | moderate | |
| Kanamycin | moderate | |
| Minocycline | moderate | |
| Mycophenolic acid | moderate | |
| Oxytetracycline | moderate | |
| Pemetrexed | moderate | |
| Picosulfuric acid | moderate | |
| Streptomycin | moderate | |
| Tetracycline | moderate | |
| Warfarin | moderate | |
| Clarithromycin | minor | |
| Erythromycin | minor | |
| Heparin | minor |
Registered Products (9)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| Piperacillin/Tazobactam | Powder for Injection 0.25 g, 2 g | 1 vial | Nabulsi Drug Store | — |
| Piperacillin/Tazobactam | Tablet 2000 mg, 250 mg | 12 vial | Petra Drug Store | — |
| Piperacillin/Tazobactam | Vial 4000 mg, 500 mg | 12 vial | Petra Drug Store | — |
| Piperacillin/Tazobactam Sandoz | Vial 0.5 g, 4 g | 1 vial pack varies | Nabulsi Drug Store | — |
| Piperacillin/Tazobactam Sandoz | Vial 0.5 g, 4 g | 10 vial pack varies | Nabulsi Drug Store | — |
| Prizma | Vial 4 g, 500 mg | 1 vial | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| Prizma Vial | Vial 2 g, 0.25 g | 1 vial | Hikma Pharmaceuticals Co.Ltd/Jordan | — |
| Yanoven 2G + | Vial 2 g, 0.25 g | 1 amp | Adonis Drug Store | — |
| Yanoven 4G + | Vial 4 g, 0.5 g | 1 vial | Adonis Drug Store | — |