Usual Adult Dose for Intraabdominal Infection

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of Escherichia coli or members of the Bacteroides fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations: 3.375 g IV every 6 hours

• May increase for infections due to Pseudomonas aeruginosa: 3.375 g IV every 4 hours or 4.5 g IV every 6 hours

Comments:

• Recommended as an initial IV regimen for empiric treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of high-risk/high-severity community-acquired extrabiliary complicated intraabdominal infection (e.g., severe physiologic disturbance, advanced age, immunocompromised state)
• Recommended for healthcare-associated intraabdominal infection, depending on local microbiologic studies
• May be used for initial empiric treatment of: high-risk/high-severity community-acquired acute cholecystitis; acute cholangitis after bilioenteric anastomosis (any severity); healthcare-associated biliary infection (any severity)
• Coadministration with other agents may be recommended.
• Current guidelines should be consulted for additional information.

International Society for Peritoneal Dialysis (ISPD) Recommendations:
Continuous (all exchanges):

• Loading dose: 4 g (piperacillin component) intraperitoneally
• Maintenance dose: 1 g (piperacillin component) intraperitoneally

Comments:

• When a surgical cause of peritoneal dialysis (PD)-related peritonitis is suspected, this drug may be considered as monotherapy.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Peritonitis

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of Escherichia coli or members of the Bacteroides fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations: 3.375 g IV every 6 hours

• May increase for infections due to Pseudomonas aeruginosa: 3.375 g IV every 4 hours or 4.5 g IV every 6 hours

Comments:

• Recommended as an initial IV regimen for empiric treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of high-risk/high-severity community-acquired extrabiliary complicated intraabdominal infection (e.g., severe physiologic disturbance, advanced age, immunocompromised state)
• Recommended for healthcare-associated intraabdominal infection, depending on local microbiologic studies
• May be used for initial empiric treatment of: high-risk/high-severity community-acquired acute cholecystitis; acute cholangitis after bilioenteric anastomosis (any severity); healthcare-associated biliary infection (any severity)
• Coadministration with other agents may be recommended.
• Current guidelines should be consulted for additional information.

International Society for Peritoneal Dialysis (ISPD) Recommendations:
Continuous (all exchanges):

• Loading dose: 4 g (piperacillin component) intraperitoneally
• Maintenance dose: 1 g (piperacillin component) intraperitoneally

Comments:

• When a surgical cause of peritoneal dialysis (PD)-related peritonitis is suspected, this drug may be considered as monotherapy.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Appendicitis

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of Escherichia coli or members of the Bacteroides fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

Surgical Infection Society (SIS) and Infectious Diseases Society of America (IDSA) Recommendations: 3.375 g IV every 6 hours

• May increase for infections due to Pseudomonas aeruginosa: 3.375 g IV every 4 hours or 4.5 g IV every 6 hours

Comments:

• Recommended as an initial IV regimen for empiric treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of high-risk/high-severity community-acquired extrabiliary complicated intraabdominal infection (e.g., severe physiologic disturbance, advanced age, immunocompromised state)
• Recommended for healthcare-associated intraabdominal infection, depending on local microbiologic studies
• May be used for initial empiric treatment of: high-risk/high-severity community-acquired acute cholecystitis; acute cholangitis after bilioenteric anastomosis (any severity); healthcare-associated biliary infection (any severity)
• Coadministration with other agents may be recommended.
• Current guidelines should be consulted for additional information.

International Society for Peritoneal Dialysis (ISPD) Recommendations:
Continuous (all exchanges):

• Loading dose: 4 g (piperacillin component) intraperitoneally
• Maintenance dose: 1 g (piperacillin component) intraperitoneally

Comments:

• When a surgical cause of peritoneal dialysis (PD)-related peritonitis is suspected, this drug may be considered as monotherapy.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Nosocomial Pneumonia

4.5 g IV every 6 hours
Duration of therapy: 7 to 14 days

Comments:

• Nosocomial pneumonia due to P aeruginosa should be treated in combination with an aminoglycoside.
• Initial presumptive therapy should start with this drug plus an aminoglycoside.
• Aminoglycoside therapy should be continued if P aeruginosa is isolated.

Use: For the treatment of moderate to severe nosocomial pneumonia due to beta-lactamase-producing isolates of Staphylococcus aureus and by piperacillin-tazobactam-susceptible Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, and P aeruginosa

IDSA and American Thoracic Society Recommendations: 4.5 g IV every 6 hours
Duration of therapy: 7 days

Comments:

• Recommended as an empiric treatment regimen for clinically suspected ventilator-associated pneumonia in units where such coverage is appropriate
• Recommended as initial empiric therapy for hospital-acquired pneumonia (non-ventilator-associated pneumonia)
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Skin or Soft Tissue Infection

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Use: For the treatment of uncomplicated and complicated skin and skin structure infections (including cellulitis, cutaneous abscesses, ischemic/diabetic foot infections) due to beta-lactamase-producing isolates of S aureus

IDSA Recommendations:

• Incisional surgical site infection: 3.375 g IV every 6 hours or 4.5 g IV every 8 hours
• Necrotizing infections of the skin, fascia, and muscle: 3.375 g IV every 6 to 8 hours
• Infection after animal bite: 3.375 g IV every 6 to 8 hours

Comments:

• Recommended as a single-drug regimen for treatment of incisional surgical site infections after intestinal or genitourinary tract surgery
• With vancomycin, recommended as a preferred regimen for the treatment of necrotizing infections of the skin, fascia, and muscle due to mixed infections
• Infection after animal bite: This drug does not provide coverage for methicillin-resistant S aureus (MRSA).
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Skin and Structure Infection

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Use: For the treatment of uncomplicated and complicated skin and skin structure infections (including cellulitis, cutaneous abscesses, ischemic/diabetic foot infections) due to beta-lactamase-producing isolates of S aureus

IDSA Recommendations:

• Incisional surgical site infection: 3.375 g IV every 6 hours or 4.5 g IV every 8 hours
• Necrotizing infections of the skin, fascia, and muscle: 3.375 g IV every 6 to 8 hours
• Infection after animal bite: 3.375 g IV every 6 to 8 hours

Comments:

• Recommended as a single-drug regimen for treatment of incisional surgical site infections after intestinal or genitourinary tract surgery
• With vancomycin, recommended as a preferred regimen for the treatment of necrotizing infections of the skin, fascia, and muscle due to mixed infections
• Infection after animal bite: This drug does not provide coverage for methicillin-resistant S aureus (MRSA).
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Pelvic Inflammatory Disease

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Use: For the treatment of postpartum endometritis or pelvic inflammatory disease due to beta-lactamase-producing isolates of E coli

Usual Adult Dose for Endometritis

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Use: For the treatment of postpartum endometritis or pelvic inflammatory disease due to beta-lactamase-producing isolates of E coli

Usual Adult Dose for Pneumonia

3.375 g IV every 6 hours
Usual duration of therapy: 7 to 10 days

Use: For the treatment of community-acquired pneumonia (moderate severity only) due to beta-lactamase-producing isolates of H influenzae

Usual Adult Dose for Surgical Prophylaxis

American Society of Health-System Pharmacists (ASHP), IDSA, SIS, and Society for Healthcare Epidemiology of America (SHEA) Recommendations:

• Preoperative dose: 3.375 g IV as a single dose
• Redosing interval (from start of preoperative dose): 2 hours

Comments:

• Recommended for perioperative prophylaxis to prevent surgical-site infections in patients undergoing liver transplantation
• This drug should be started within 60 minutes before surgical incision.
• A single prophylactic dose is usually sufficient; if prophylaxis is continued postoperatively, duration should be less than 24 hours.
• To ensure adequate serum and tissue drug levels, readministration may be needed if the procedure duration exceeds the recommended redosing interval.
• Redosing may be needed if drug half-life is shortened (e.g., extensive burns) or if prolonged/excessive bleeding during surgery; redosing may not be needed if drug half-life is prolonged (e.g., renal dysfunction).
• Coadministration with other agents may be recommended.
• Current guidelines should be consulted for additional information.

Usual Adult Dose for Pyelonephritis

Some experts recommend: 3.375 to 4.5 g IV every 6 to 8 hours
Duration of therapy: About 14 days

Comments:

• Dose and therapy duration depend on the nature and severity of the infection.
• Once the patient is stable and able to tolerate oral medications, oral antibiotic therapy may be substituted according to microbiology sensitivity data.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Intraabdominal Infection

DOSE EXPRESSED AS PIPERACILLIN-TAZOBACTAM:
2 to 9 months: 90 mg/kg IV every 8 hours
Older than 9 months:

• Up to 40 kg: 112.5 mg/kg IV every 8 hours
• Greater than 40 kg: 3.375 g IV every 6 hours

DOSE EXPRESSED AS PIPERACILLIN:
2 to 9 months: 80 mg/kg (piperacillin component) IV every 8 hours
Older than 9 months:

• Up to 40 kg: 100 mg/kg (piperacillin component) IV every 8 hours
• Greater than 40 kg: 3 g (piperacillin component) IV every 6 hours

Usual Duration of Therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of E coli or members of the B fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

SIS and IDSA Recommendations: 200 to 300 mg/kg/day (piperacillin component) IV in divided doses every 6 to 8 hours
Maximum dose: 12 g/day (piperacillin component)

Comments:

• Recommended as an initial IV regimen for treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of community-acquired extrabiliary complicated intraabdominal infection
• Doses should be maximized if undrained intraabdominal abscess may be present.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Peritonitis

DOSE EXPRESSED AS PIPERACILLIN-TAZOBACTAM:
2 to 9 months: 90 mg/kg IV every 8 hours
Older than 9 months:

• Up to 40 kg: 112.5 mg/kg IV every 8 hours
• Greater than 40 kg: 3.375 g IV every 6 hours

DOSE EXPRESSED AS PIPERACILLIN:
2 to 9 months: 80 mg/kg (piperacillin component) IV every 8 hours
Older than 9 months:

• Up to 40 kg: 100 mg/kg (piperacillin component) IV every 8 hours
• Greater than 40 kg: 3 g (piperacillin component) IV every 6 hours

Usual Duration of Therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of E coli or members of the B fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

SIS and IDSA Recommendations: 200 to 300 mg/kg/day (piperacillin component) IV in divided doses every 6 to 8 hours
Maximum dose: 12 g/day (piperacillin component)

Comments:

• Recommended as an initial IV regimen for treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of community-acquired extrabiliary complicated intraabdominal infection
• Doses should be maximized if undrained intraabdominal abscess may be present.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Appendicitis

DOSE EXPRESSED AS PIPERACILLIN-TAZOBACTAM:
2 to 9 months: 90 mg/kg IV every 8 hours
Older than 9 months:

• Up to 40 kg: 112.5 mg/kg IV every 8 hours
• Greater than 40 kg: 3.375 g IV every 6 hours

DOSE EXPRESSED AS PIPERACILLIN:
2 to 9 months: 80 mg/kg (piperacillin component) IV every 8 hours
Older than 9 months:

• Up to 40 kg: 100 mg/kg (piperacillin component) IV every 8 hours
• Greater than 40 kg: 3 g (piperacillin component) IV every 6 hours

Usual Duration of Therapy: 7 to 10 days

Uses: For the treatment of appendicitis (complicated by rupture or abscess) and peritonitis due to beta-lactamase-producing isolates of E coli or members of the B fragilis group (B fragilis, B ovatus, B thetaiotaomicron, or B vulgatus)

SIS and IDSA Recommendations: 200 to 300 mg/kg/day (piperacillin component) IV in divided doses every 6 to 8 hours
Maximum dose: 12 g/day (piperacillin component)

Comments:

• Recommended as an initial IV regimen for treatment of complicated intraabdominal infection
• May be used for initial empiric treatment of community-acquired extrabiliary complicated intraabdominal infection
• Doses should be maximized if undrained intraabdominal abscess may be present.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Nosocomial Pneumonia

DOSE EXPRESSED AS PIPERACILLIN-TAZOBACTAM:
2 to 9 months: 90 mg/kg IV every 6 hours
Older than 9 months:

• Up to 40 kg: 112.5 mg/kg IV every 6 hours
• Greater than 40 kg: 4.5 g IV every 6 hours

DOSE EXPRESSED AS PIPERACILLIN:
2 to 9 months: 80 mg/kg (piperacillin component) IV every 6 hours
Older than 9 months:

• Up to 40 kg: 100 mg/kg (piperacillin component) IV every 6 hours
• Greater than 40 kg: 4 g (piperacillin component) IV every 6 hours

Duration of Therapy: 7 to 14 days

Comments:

• Nosocomial pneumonia due to P aeruginosa should be treated in combination with an aminoglycoside.
• Pediatric patients over 40 kg: Initial presumptive therapy should start with this drug plus an aminoglycoside.
• Pediatric patients over 40 kg: Aminoglycoside therapy should be continued if P aeruginosa is isolated.

Use: For the treatment of moderate to severe nosocomial pneumonia due to beta-lactamase-producing isolates of S aureus and by piperacillin-tazobactam-susceptible A baumannii, H influenzae, K pneumoniae, and P aeruginosa

Usual Pediatric Dose for Bacterial Infection

American Academy of Pediatrics Recommendations:
Neonates:

• Postmenstrual age up to 30 weeks: 100 mg/kg (piperacillin component) IV every 8 hours
• Postmenstrual age over 30 weeks: 80 mg/kg (piperacillin component) IV every 6 hours

1 month or older: 240 to 300 mg/kg/day (piperacillin component) IV divided in 3 to 4 doses

• Maximum dose: 16 g/day (piperacillin component)

1 month or older with cystic fibrosis: 400 to 600 mg/kg/day (piperacillin component) IV divided in 6 doses may be appropriate in some patients

• Maximum dose: 24 g/day (piperacillin component)

Comments:

• Patients 1 month or older: Extended infusion may be needed for susceptible dose-dependent infections.
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Endocarditis

American Heart Association Recommendations:
Children and adolescents: 240 mg/kg/day (piperacillin component) IV in divided doses every 8 hours
Maximum dose: 18 g/day (piperacillin component)
Duration of therapy: At least 6 weeks

Comments:

• With an aminoglycoside, recommended as an alternative regimen for the treatment of infective endocarditis due to gram-negative enteric bacilli
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Skin or Soft Tissue Infection

IDSA Recommendations:
1 month or older: 60 to 75 mg/kg (piperacillin component) IV every 6 hours
Maximum dose: 3 g/dose (piperacillin component)

Comments:

• With vancomycin, recommended as a preferred regimen for the treatment of necrotizing infections of the skin, fascia, and muscle due to mixed infections
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Skin and Structure Infection

IDSA Recommendations:
1 month or older: 60 to 75 mg/kg (piperacillin component) IV every 6 hours
Maximum dose: 3 g/dose (piperacillin component)

Comments:

• With vancomycin, recommended as a preferred regimen for the treatment of necrotizing infections of the skin, fascia, and muscle due to mixed infections
• Current guidelines should be consulted for additional information.

Usual Pediatric Dose for Surgical Prophylaxis

ASHP, IDSA, SIS, and SHEA Recommendations:
Preoperative dose:

• Infants 2 to 9 months: 80 mg/kg (piperacillin component) IV as a single dose
• Children older than 9 months and up to 40 kg: 100 mg/kg (piperacillin component) IV as a single dose
• Maximum dose: 3 g/dose (piperacillin component)

Redosing interval (from start of preoperative dose): 2 hours

Comments:

• Recommended for perioperative prophylaxis to prevent surgical-site infections in patients undergoing liver transplantation
• This drug should be started within 60 minutes before surgical incision.
• A single prophylactic dose is usually sufficient; if prophylaxis is continued postoperatively, duration should be less than 24 hours.
• To ensure adequate serum and tissue drug levels, readministration may be needed if the procedure duration exceeds the recommended redosing interval.
• Redosing may be needed if drug half-life is shortened (e.g., extensive burns) or if prolonged/excessive bleeding during surgery; redosing may not be needed if drug half-life is prolonged (e.g., renal dysfunction).
• Coadministration with other agents may be recommended.
• Current guidelines should be consulted for additional information.

Renal Dose Adjustments

Adult patients:
CrCl greater than 40 mL/min: No adjustment recommended.

CrCl 20 to 40 mL/min:

• Nosocomial pneumonia: 3.375 g IV every 6 hours
• Other indications: 2.25 g IV every 6 hours

CrCl less than 20 mL/min:

• Nosocomial pneumonia: 2.25 g IV every 6 hours
• Other indications: 2.25 g IV every 8 hours

Pediatric patients: Data not available

Liver Dose Adjustments

Hepatic cirrhosis: No adjustment recommended.

Precautions

CONTRAINDICATIONS:
History of allergic reactions to any penicillin, cephalosporin, or beta-lactamase inhibitor

Safety and efficacy have not been established in patients younger than 2 months.

Consult WARNINGS section for additional precautions.

Dialysis

Adult patients:
Hemodialysis, CAPD:

• Nosocomial pneumonia: 2.25 g IV every 8 hours
• Other indications: 2.25 g IV every 12 hours

Continuous venovenous hemofiltration (CVVH): Some experts recommend piperacillin-tazobactam 2.25 to 3.375 g every 8 hours for initial therapy of patients undergoing CVVH, and then intermittent doses of piperacillin alone to prevent tazobactam accumulation.

Pediatric patients: Data not available

Comments:

• A supplemental dose of 0.75 g piperacillin-tazobactam should be given after each hemodialysis session on hemodialysis days.
• No supplemental dose is needed for CAPD patients.
• Clearance may be significantly increased in patients undergoing continuous renal replacement therapy (CRRT) and higher doses may be necessary which should be individualized based on estimated piperacillin-tazobactam clearance. In addition, tazobactam has a longer half-life than piperacillin, resulting in relative serum level increases compared to piperacillin.

Other Comments

Dose expressed as piperacillin-tazobactam unless otherwise specified.

4.5 g piperacillin-tazobactam contains 4 g piperacillin and 500 mg tazobactam
3.375 g piperacillin-tazobactam contains 3 g piperacillin and 375 mg tazobactam
2.25 g piperacillin-tazobactam contains 2 g piperacillin and 250 mg tazobactam
0.75 g piperacillin-tazobactam contains 670 mg piperacillin and 80 mg tazobactam
112.5 mg/kg piperacillin-tazobactam contains 100 mg/kg piperacillin and 12.5 mg/kg tazobactam
90 mg/kg piperacillin-tazobactam contains 80 mg/kg piperacillin and 10 mg/kg tazobactam

Administration advice:

• Administer via IV infusion over 30 minutes.
• During infusion of this drug, discontinue the primary infusion solution.
• Do not mix with other drugs in a syringe or infusion bottle.
• Galaxy Containers: Do not use plastic containers in series connections.
• Reconstitute, dilute, and administer this drug and aminoglycosides separately when concurrent use of aminoglycosides is indicated; consult the manufacturer product information regarding coadministration via Y-site infusion.

Storage requirements:

• Galaxy Containers: Store at or below -20C (-4F); thawed solution is stable for 24 hours at 20C to 25C (68F to 77F) or for 14 days at 2C to 8C (36F to 46F); do not refreeze.
• Vials: The manufacturer product information should be consulted regarding storage and stability of reconstituted and/or further diluted solutions.

Reconstitution/preparation techniques:

• Galaxy Containers: Thaw frozen container at room temperature 20C to 25C (68F to 77F) or in refrigerator 2C to 8C (36F to 46F); do not force thaw by immersion in water baths or by microwave irradiation.
• Vials: Reconstitution and further dilution needed; the manufacturer product information should be consulted.

IV compatibility:

• Compatible reconstitution diluents for vials: 0.9% sodium chloride injection; sterile water for injection; dextrose 5%; bacteriostatic saline/parabens; bacteriostatic water/parabens; bacteriostatic saline/benzyl alcohol
• Compatible IV solutions for vials: 0.9% sodium chloride injection; sterile water for injection; dextran 6% in saline; dextrose 5%
• Lactated Ringers Solution is compatible only with the reformulated product containing edetate disodium dihydrate (EDTA); compatible for coadministration via Y-site.
• Incompatible: Solutions containing only sodium bicarbonate; solutions that alter pH significantly; blood products; albumin hydrolysates
• Galaxy Containers: Do not add supplementary medication; product containing EDTA is compatible for coadministration via Y-site IV tube with Lactated Ringers injection, USP.

General:

• This drug is for the treatment of moderate to severe infections due to susceptible isolates of the designated bacteria.
• To reduce the development of drug-resistant organisms and maintain effective therapy, this drug should be used only to treat or prevent infections proven or strongly suspected to be caused by susceptible bacteria.
• Culture and susceptibility information should be considered when selecting/modifying antibacterial therapy or, if no data are available, local epidemiology and susceptibility patterns may be considered when selecting empiric therapy.
• Sodium content is about 2.84 mEq (65 mg) per gram of piperacillin; at usual recommended doses, patients would receive about 34.1 to 45.5 mEq/day (780 to 1040 mg/day) of sodium.

Monitoring:

• Hematologic: Hematopoietic function (periodically, especially during prolonged therapy)
• Metabolic: Electrolytes in patients with low potassium reserves (periodically)
• Nervous System: For signs/symptoms of neuromuscular excitability or seizures in patients with renal dysfunction or seizure disorders
• Renal: Renal function in critically ill patients (during therapy); renal function in elderly patients

Patient advice:

• Avoid missing doses and complete the entire course of therapy.
• Consult physician at once if watery and bloody stools (with or without stomach cramps and fever) develop.