Community-acquired pneumonia: IM, IV: Usual dosage: 6 to 8 g daily (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours
Severe infections (eg, gynecologic, intra-abdominal, nosocomial pneumonia, septicemia, skin/soft tissue): IV: Usual dosage: 12 to 18 g daily (200 to 300 mg/kg daily) in divided doses every 4 to 6 hours (maximum: 24 g daily)
Urethritis (gonococcal, uncomplicated): IM: 2 g once (Note: Administer probenecid 30 minutes prior to piperacillin)
Urinary tract infection (complicated): IV: Usual dosage: 8 to 16 g daily (125 to 200 mg/kg daily) in divided doses every 6 to 8 hours
Urinary tract infection (uncomplicated): IM, IV: Usual dosage: 6 to 8 g daily (100 to 125 mg/kg daily) in divided doses every 6 to 12 hours
CrCl >40 mL/minute or serum creatinine 1.5 to 3 mg/dL: No dosage adjustment necessary.
CrCl 20-40 mL/minute or serum creatinine 3.1 to 5 mg/dL:
Urinary tract infection (uncomplicated): No dosage adjustment necessary.
Urinary tract infection (complicated): 3 g every 8 hours
Severe systemic infection: 4 g every 8 hours
CrCl <20 mL/minute or serum creatinine >5 mg/dL:
Urinary tract infection (complicated/uncomplicated): 3 g every 12 hours
Severe systemic infection: 4 g every 12 hours
Hemodialysis: Severe systemic infection: 2 g every 8 hours; administer 1 g supplemental dose after each dialysis session; dialyzable (30% to 50%)
No dosage adjustment provided in manufacturer’s labeling.
Usual dosage range: Children ≥12 years and Adolescents: IM, IV: Refer to adult dosing.
Children ≥12 years and Adolescents: There are no dosage adjustments provided in the manufacturer's labeling; however, the following have been used by some clinicians (Aronoff 2007): Note: Dosage recommendations are based on the piperacillin component. Dosing based on a usual dose of 200 to 300 mg piperacillin kg/day in divided doses every 6 hours.
GFR >50 mL/minute/1.73 m2: No adjustment required
GFR 30 to 50 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 6 hours
GFR <30 mL/minute/1.73 m2: 35 to 50 mg piperacillin/kg/dose every 8 hours
Intermittent hemodialysis (IHD): Removed by hemodialysis; dosing adjustment suggested
There are no dosage adjustments provided in manufacturer’s labeling; based on experience with piperacillin/tazobactam, no adjustment necessary.
Refer to adult dosing. Dosage adjustment may be necessary for renal impairment.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Injection:
Generic: 2 g (1 ea); 3 g (1 ea); 4 g (1 ea)
Not available in the US
IV: Rapid administration can lead to seizures. Administer by IV injection over 3 to 5 minutes or by intermittent infusion over 20 minutes to 2 hours.
IM: IM injection should be administered into the upper outer quadrant of the buttocks. Do not administer more than 2 g per IM injection site.
IM: Administer into the upper outer quadrant of the buttocks (gluteus maximus). Do not administer more than 2 g per injection site.
Bolus: Administer slow IV over 3 to 5 minutes to avoid vein irritation. Rapid administration can lead to seizures.
Intermittent infusion: Administer over 20 to 30 minutes; however, longer infusion times (eg, 2 hours) may be used.
Note: Not approved in the US
Infection: Treatment of infection caused by susceptible gram-negative/gram-positive aerobic and anaerobic bacteria including intra-abdominal infections, septicemia, lower respiratory tract infections, skin and soft tissue infections, bone and joint infections, gynecological infections, urinary tract infections (complicated and uncomplicated), and urethritis (uncomplicated); may also be used to treat mixed infections due to susceptible streptococci
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined.
Cardiovascular: Local thrombophlebitis
Central nervous system: Confusion, drowsiness, myoclonus, seizure
Dermatologic: Skin rash, toxic epidermal necrolysis, urticaria
Endocrine & metabolic: Electrolyte disturbance, hypokalemia
Hematologic & oncologic: Abnormal platelet aggregation (high doses), agranulocytosis, hemolytic anemia, pancytopenia, positive direct Coombs test, prolonged prothrombin time (high doses)
Hypersensitivity: Anaphylaxis, hypersensitivity reaction
Immunologic: Jarisch-Herxheimer reaction
Renal: Acute interstitial nephritis, acute renal failure
Hypersensitivity to any of the penicillins and/or cephalosporins or any component of the formulation; hypersensitivity to local anesthetics of the amide type (when reconstituted with lidocaine for IM use)
Concerns related to adverse effects:
• 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.
• 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.
Acemetacin: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Aminoglycosides: Penicillins may decrease the serum concentration of Aminoglycosides. Primarily associated with extended spectrum penicillins, and patients with renal dysfunction. Risk C: Monitor therapy
BCG (Intravesical): Antibiotics may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Vaccine (Immunization): Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization). Risk C: Monitor therapy
Cholera Vaccine: Antibiotics may diminish the therapeutic effect of Cholera Vaccine. Management: Avoid cholera vaccine in patients receiving systemic antibiotics, and within 14 days following the use of oral or parenteral antibiotics. Risk X: Avoid combination
Dichlorphenamide: Penicillins may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy
Dichlorphenamide: OAT1/3 Inhibitors may increase the serum concentration of Dichlorphenamide. Risk C: Monitor therapy
Flucloxacillin: Piperacillin may increase the serum concentration of Flucloxacillin. Risk C: Monitor therapy
Lactobacillus and Estriol: Antibiotics may diminish the therapeutic effect of Lactobacillus and Estriol. Risk C: Monitor therapy
Methotrexate: Penicillins may increase the serum concentration of Methotrexate. Risk C: Monitor therapy
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy
Probenecid: May increase the serum concentration of Penicillins. Risk C: Monitor therapy
Sodium Picosulfate: Antibiotics may diminish the therapeutic effect of Sodium Picosulfate. Management: Consider using an alternative product for bowel cleansing prior to a colonoscopy in patients who have recently used or are concurrently using an antibiotic. Risk D: Consider therapy modification
Tetracyclines: May diminish the therapeutic effect of Penicillins. Risk C: Monitor therapy
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Management: Avoid use of live attenuated typhoid vaccine (Ty21a) in patients being treated with systemic antibacterial agents. Postpone vaccination until 3 days after cessation of antibiotics and avoid starting antibiotics within 3 days of last vaccine dose. Risk D: Consider therapy modification
Vancomycin: Piperacillin may enhance the nephrotoxic effect of Vancomycin. Risk C: Monitor therapy
Vecuronium: Piperacillin may enhance the neuromuscular-blocking effect of Vecuronium. Risk C: Monitor therapy
Vitamin K Antagonists (eg, warfarin): Penicillins may enhance the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
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).
As a class, penicillin antibiotics are widely used in pregnant women. Based on available data, penicillin antibiotics are generally considered compatible for use during pregnancy (Ailes 2016; Bookstaver 2015; Crider 2009; Damkier 2019; Lamont 2014; Muanda 2017a; Muanda 2017b).
Antibiotic prophylaxis with piperacillin may be appropriate for the prevention of endocarditis for patients undergoing obstetric and gynecologic procedures (consult current recommendations) (SOGC [Van Eyk 2018]; SOGC [van Schalkwyk 2017]).
Piperacillin is present in breast milk.
The manufacturer reports small amounts of piperacillin are present in breast milk and recommends that caution be exercised when administering piperacillin to nursing women. In general, antibiotics that are present in breast milk may cause nondose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush or diarrhea (WHO 2002).
Sodium content of 1 g: 1.85 mEq (42.5 mg)
Observe for signs and symptoms of anaphylaxis during first dose; with extended therapy consider monitoring of electrolytes and cardiac status (patients with impaired cardiac function), serum creatinine, BUN, hepatic function, and CBC.
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.
Absorption: IM: Rapid
Protein binding: ~16%
Half-life elimination (dose dependent; prolonged with renal impairment): Adults: ~1 hour (decreased in patients with cystic fibrosis)
Time to peak, serum: IM: 30 minutes
Excretion: Primarily urine; partially feces