Piperacillin + Tazobactam

Pharmacologic Category

Antibiotic, Penicillin

Dosing: Adult

Note: Adult doses are expressed as the combined amount of piperacillin and tazobactam. Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified as the extended infusion method over 4 hours or continuous infusion method over 24 hours (off-label methods).

Usual dosage range:

Traditional infusion method (over 30 minutes): IV:

Mild to moderate infections: 3.375 g every 6 hours.

Severe infections: 4.5 g every 6 to 8 hours (Cornely 2004; Gyssens 2011; Saltoglu 2010).

For coverage of Pseudomonas aeruginosa: 4.5 g every 6 hours. Usual maximum dose: 18 g/day.

Extended-infusion method (off-label method):

IV: 3.375 or 4.5 g every 8 hours infused over 4 hours (Lodise 2007; Shea 2009; Yang 2015). Note: A loading dose of 3.375 to 4.5 g over 30 minutes can be given, especially when rapid attainment of therapeutic drug concentrations is necessary (eg, sepsis) (SCCM [Rhodes 2017]).

Continuous-infusion method (off-label method):

IV: 18 g infused over 24 hours (Abdul-Aziz 2016); may give a loading dose of 4.5 g over 30 minutes, especially when rapid attainment of therapeutic drug concentrations (eg, sepsis) is desired (Abdul-Aziz 2016; SCCM [Rhodes 2017]).

Extended and continuous infusion methods are based largely on pharmacokinetic and pharmacodynamic modeling data; clinical efficacy data are limited (Abdul-Aziz 2016; Lodise 2007; MacVane 2014; Moehring 2019a; Rhodes 2014; Vardakas 2018).

Indication-specific dosing:

Bite wound infection, treatment (animal or human bite) (off-label use):

IV: 3.375 g every 6 to 8 hours. Duration of treatment for established infection (which may include oral step-down therapy) is typically 5 to 14 days. Additional coverage for methicillin-resistant Staphylococcus aureus may be needed for empiric treatment (Baddour 2019a; Baddour 2019b; IDSA [Stevens 2014]).

Bloodstream infection (gram-negative bacteremia) (off-label use):

Note: For empiric therapy of known or suspected gram-negative (including P. aeruginosa) bloodstream infection in patients with neutropenia, severe burns, sepsis, or septic shock, some experts recommend giving piperacillin and tazobactam in combination with a second gram-negative active agent (Kanj 2019a; SCCM [Rhodes 2017]). Some experts also prefer the extended-infusion method in critical illness or to optimize exposure if treating a susceptible organism with an elevated minimum inhibitory concentration (Moehring 2019a; SCCM [Rhodes 2017]).

Community-acquired infection, immunocompetent host: IV: 3.375 g every 6 hours (Moehring 2019b).

Health care-associated infection, including catheter-related, immunosuppressed host, or for coverage of P. aeruginosa: IV: 4.5 g every 6 hours (IDSA [Mermel 2009]; Moehring 2019b).

Duration of therapy: Usual duration is 7 to 14 days, depending on source, pathogen, extent of infection, and clinical response (Moehring 2019b); a 7-day duration is recommended for patients with uncomplicated Enterobacteriaceae infection who respond appropriately to antibiotic therapy (Chotiprasitsakul 2018; Moehring 2019b; Yahav 2018). Note: If neutropenic, extend treatment until afebrile for 2 days and neutrophil recovery (ANC ≥500 cells/mm³ and increasing) (IDSA [Freifeld 2011]). For P. aeruginosa bacteremia in neutropenic patients, some experts treat for a minimum of 14 days and until recovery of neutrophils (Kanj 2019a).

Cystic fibrosis, severe acute pulmonary exacerbation or failure of oral therapy, for coverage of P. aeruginosa (off-label use):

IV: 4.5 g every 6 hours usually as part of an appropriate combination regimen (Flume 2009; Simon 2019). Note: Some experts prefer the extended or continuous infusion method to optimize exposure (Butterfield 2014; Simon 2019). Duration is usually 10 days to 3 weeks or longer based on clinical response (Flume 2009; Simon 2019).

Diabetic foot infection, moderate to severe:

IV: 3.375 g every 6 hours or 4.5 g every 8 hours (Gyssens 2011; Saltoglu 2010; Tan 1993). For treatment of P. aeruginosa infection: 4.5 g every 6 hours (Weintrob 2019). Note: Empiric Pseudomonas coverage with this dose is usually not indicated unless patient is at risk (eg, significant water exposure, warm climate). Duration (which may include oral step-down therapy) is usually 2 to 4 weeks in the absence of osteomyelitis (IDSA [Lipsky 2012]; Weintrob 2019).

Intra-abdominal infection:

Cholecystitis, acute: IV: 3.375 or 4.5 g every 6 hours; continue for 1 day after gallbladder removal or until clinical resolution in patients managed nonoperatively (Gomi 2018; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]; Vollmer 2019).

Other intra-abdominal infection (eg, cholangitis, perforated appendix, diverticulitis, intra-abdominal abscess):

IV: 3.375 g or 4.5 g every 6 hours. Total duration of therapy (which may include oral step-down therapy) is 4 to 7 days following adequate source control (Barshak 2019; Gomi 2018; Pemberton 2019; SIS [Mazuski 2017]; SIS/IDSA [Solomkin 2010]); for infections managed without surgical or percutaneous intervention, a longer duration may be necessary (Barshak 2019; Pemberton 2019). Note: For patients who are critically ill or at risk for infection with drug-resistant pathogens, some experts favor the extended infusion method (Barshak 2019; WSES [Sartelli 2017).

Note: Reserve 4.5 g dose for health care-associated infection, severe community-acquired infection, or patients with community-acquired infection at high risk of adverse outcome and/or resistance (Barshak 2019; SIS/IDSA [Solomkin 2010]).

Malignant (necrotizing) external otitis, hospitalized patients (alternative agent) (off-label use): IV: 4.5 g every 6 hours. Total duration of therapy, including oral step-down, is 6 to 8 weeks (Grandis 2018).

Neutropenic fever, high-risk cancer patients (empiric therapy) (off-label use):

Note: High-risk patients are those expected to have an ANC ≤100 cells/mm³ for >7 days or an ANC ≤100 cells/mm³ for any expected duration if there are ongoing comorbidities (eg, sepsis, mucositis, significant hepatic or renal dysfunction) (IDSA [Freifeld 2011]); some experts use an ANC cutoff <500 cells/mm³ to define high-risk patients (Wingard 2019).

IV: 4.5 g every 6 to 8 hours until afebrile for ≥48 hours and resolution of neutropenia (ANC ≥500 cells/mm³ and increasing) or standard duration for the specific infection identified, if longer than the duration for neutropenia. If there is significant concern for Pseudomonas infection (particularly in those who are severely ill or were not receiving fluoroquinolone prophylaxis), 4.5 g every 6 hours should be given. Additional agent(s) may be needed depending on clinical status (IDSA [Freifeld 2011]; Wingard 2019). Some experts prefer the extended-infusion method, particularly in those who are critically ill (Moehring 2019a; SCCM [Rhodes 2017]).

Pneumonia:

Community-acquired pneumonia: For empiric therapy of inpatients at risk of infection with a resistant gram-negative pathogen(s), including P. aeruginosa:

IV: 4.5 g every 6 hours as part of an appropriate combination regimen. Total duration (which may include oral step-down therapy) is for a minimum of 5 days; a longer course may be required for P. aeruginosa infection. Patients should be clinically stable with normal vital signs prior to discontinuation (ATS/IDSA [Metlay 2019]).

Hospital-acquired or ventilator-associated pneumonia: For empiric therapy or pathogen-specific therapy of resistant gram-negative pathogen(s), including P. aeruginosa:

IV: 4.5 g every 6 hours, as part of an appropriate combination regimen. Duration of therapy varies based on disease severity and response to therapy; treatment is typically given for 7 days (IDSA/ATS [Kalil 2016]), but a longer course may be required for severe or complicated infection or for P. aeruginosa infection (Kanj 2019b). Note: Some experts prefer the extended-infusion method, particularly in those who are critically ill (Moehring 2019a; Rhodes 2014).

Sepsis and septic shock (broad-spectrum empiric therapy, including P.aeruginosa) (off-label use): IV: 4.5 g every 6 hours in combination with other appropriate agent(s) (Kanj 2019c). Initiate therapy as soon as possible and within 1 hour of recognition of sepsis or septic shock. Usual duration of treatment is dependent on underlying source, but is typically 7 to 10 days or longer, depending upon clinical response (SCCM [Rhodes 2017]). Consider discontinuation if a noninfectious etiology is identified (SCCM [Rhodes 2017]; Schmidt 2019). Some experts prefer the extended- or continuous-infusion method (Moehring 2019a; SCCM [Rhodes 2017]).

Skin and soft tissue infection (moderate to severe infection, necrotizing infection, select surgical site infections [intestinal, GU tract]), broad-spectrum empiric coverage, including P. aeruginosa: IV: 3.375 g every 6 hours or 4.5 g every 8 hours as part of an appropriate combination regimen (IDSA [Stevens 2014]). For treatment of P. aeruginosa infection: 4.5 g every 6 hours (Kanj 2019c). Usual duration is 10 to 14 days based on clinical response; for necrotizing infection, continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for ≥48 hours (IDSA [Stevens 2014]; Kanj 2019c).

Urinary tract infection, complicated (including pyelonephritis) (off-label use): IV: 3.375 g every 6 hours or, if Pseudomonas is a concern, 4.5 g every 6 hours. Note: Switch to an appropriate oral regimen once patient has improvement in symptoms or if culture and susceptibility results allow; duration of therapy depends on the antimicrobial chosen to complete the regimen and ranges from 5 to 14 days. If piperacillin and tazobactam is continued for the entire treatment course, the duration of therapy is 10 to 14 days (Hooton 2019).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

Altered kidney function: IV:

Note: Infusion method: Dosing is presented based on the traditional infusion method over 30 minutes, unless otherwise specified as the extended infusion method over 4 hours (off-label method).

When utilizing extended infusions, a loading dose of 3.375 to 4.5 g over 30 minutes can be given, especially when rapid attainment of therapeutic drug concentrations is necessary (eg, sepsis) (SCCM [Rhodes 2017]).

Piperacillin/Tazobactam Dose Adjustments for Kidney Function^a,b

Traditional infusion method (over 30 minutes)

Extended infusion method (over 4 hours)

CrCl (mL/minute)

If the usual recommended dose is 3.375 g every 6 hours

If the usual recommended dose is 4.5 g every 6 hours

If the usual recommended dose is 3.375 g infused over 4 hours every 8 hours

^aChoose the usual recommended dose based on indication and disease severity (see adult dosing), then choose the adjusted dose from that column corresponding to the patient's CrCl.

^bPatel 2010; Thabit 2017; expert opinion; manufacturer's labeling.

100 to <130

Extended infusion preferred

Extended infusion preferred

3.375 or 4.5 g infused over 4 hours every 6 hours

40 to <100 (usual recommended dose)

3.375 g every 6 hours

4.5 g every 6 hours

3.375 g infused over 4 hours every 8 hours

20 to <40

2.25 g every 6 hours

4.5 g every 8 hours or 3.375 g every 6 hours

3.375 g infused over 4 hours every 8 to 12 hours

<20

2.25 g every 8 hours

4.5 g every 12 hours or 2.25 g every 6 hours

3.375 g infused over 4 hours every 12 hours

Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m²): Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns or hematological malignancies. An 8 to 24 hour measured urinary creatinine clearance is necessary to identify these patients (Bilbao-Meseguer 2018; Udy 2010).

CrCl 130 to <170 mL/minute: IV: Loading dose: 4.5 g, followed immediately by a daily continuous infusion of 18 g over 24 hours (Carrié 2018).

CrCl ≥170 mL/minute: IV: Loading dose: 4.5 g, followed immediately by a daily continuous infusion of 22.5 g over 24 hours (Carrié 2018).

Hemodialysis, intermittent (thrice weekly): Dialyzable (30% to 40%):

IV: 4.5 g every 12 hours or 2.25 g every 8 hours (Thabit 2017; manufacturer's labeling); administration of scheduled doses after hemodialysis on dialysis days is preferred but not required (expert opinion).

Peritoneal dialysis: Dialyzable (6% of piperacillin, 21% of tazobactam):

IV: 4.5 g every 12 hours or 2.25 g every 8 hours (Debruyne 1990; Manley 2000).

CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement (Jamal 2014). Recommendations assume high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (~1,500 to 3,000 mL/hour), unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection [Varghese 2014]) and consideration of initial loading doses. Close monitoring of response and adverse reactions due to drug accumulation is important.

CVVH/CVVHD/CVVHDF: Note: Given piperacillin/tazobactam’s favorable safety profile, some experts recommend initiating therapy with relatively high doses (especially in critically ill patients) (Hayashi 2010; Jamal 2015). Dose should be adjusted during CRRT interruptions as ongoing dosing may lead to accumulation and potential increased risk of toxicity.

IV: 4.5 g every 8 hours (Arzuaga 2005; Asin-Prieto 2014; Shotwell 2016; Varghese 2014) or 4.5 g loading dose followed by 2.25 g every 6 hours (Jamal 2015).

Continuous IV infusion: 4.5 g loading dose (expert opinion) followed immediately by a 9 g over 24 hours daily maintenance dose (Jamal 2015).

PIRRT (eg, sustained low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection). Close monitoring of response and adverse reactions due to drug accumulation is important.

IV:

Sustained low-efficiency dialysis (8-hour daily sessions with blood flow rate 200 mL/minute and effluent flow rate 300 mL/minute): 3.375 g every 8 hours (Kanji 2018).

Extended high-volume hemofiltration (10-hour sessions with blood flow rate 200 mL/minute and effluent flow rate >500 mL/minute): 4.5 g every 8 hours (Tamme 2016).

Dosing: Hepatic Impairment: Adult

No dosage adjustment necessary.

Dosing: Pediatric

Note: Zosyn (piperacillin/tazobactam) is a combination product; each 3.375 g vial contains 3 g piperacillin sodium and 0.375 g tazobactam sodium in an 8:1 ratio. Dosage recommendations are based on the piperacillin component. Some centers divide doses every 6 hours for enhanced pharmacodynamic profile. Unless otherwise specified, dosing presented is based on traditional infusion method (IV infusion over 30 minutes). Dosing is presented in mg/kg/dose and mg/kg/day; use precaution.

General dosing, susceptible infection: Severe infection:

Traditional dosing:

Infants <2 months: IV: 240 to 300 mg piperacillin/kg/day divided in 3 to 4 doses; maximum daily dose: 16 g/day (Red Book [AAP 2018]); some experts have recommended 80 mg piperacillin/kg/dose every 4 hours based on a pharmacokinetic study (Cohen-Wolkowiez 2014).

Infants ≥2 months, Children, and Adolescents: IV: 240 to 300 mg piperacillin/kg/day divided in 3 to 4 doses; maximum daily dose: 16 g/day (Red Book [AAP 2018]).

Extended infusion dosing: Limited data available: Children and Adolescents: IV: 100 mg piperacillin/kg/dose infused over 4 hours every 6 to 8 hours; dosing based on pharmacokinetic and pharmacodynamic studies as well as a retrospective case series (Cies 2014; Knoderer 2017; Nichols 2016a; Tamma 2012).

Appendicitis and/or peritonitis: IV:

Infants 2 to 9 months: 80 mg of piperacillin/kg/dose every 8 hours.

Infants >9 months and Children weighing ≤40 kg: 100 mg piperacillin/kg/dose every 8 hours; maximum dose: 3,000 mg piperacillin/dose.

Children weighing >40 kg and Adolescents: 3,000 mg piperacillin every 6 hours; maximum daily dose: 16 g piperacillin/day.

Cystic fibrosis, pseudomonal lung infection: Infants, Children, and Adolescents: Note: Multiple dosing approaches have been evaluated; optimal dose may vary based on disease severity, susceptibility patterns (eg, MIC), or patient tolerability:

Standard dosing range: IV: 240 to 400 mg piperacillin/kg/day divided every 8 hours (Kliegman 2011); others have used 350 to 400 mg/kg/day divided every 4 hours in early piperacillin trials (Zobell 2013).

High dose: Limited data available: IV: 450 mg piperacillin/kg/day divided every 4 to 6 hours or 600 mg piperacillin/kg/day divided every 4 hours has been described from early studies of piperacillin alone; usual maximum daily dose: 18 to 24 g piperacillin/day. Note: Piperacillin doses >600 mg/kg/day or an extended duration of therapy (>14 days) have been associated with dose-related adverse effects including serum sickness, immune-mediated hemolytic anemia and bone marrow suppression (Zobell 2013).

Endocarditis, treatment: Children and Adolescents: IV: 240 mg piperacillin/kg/day divided every 8 hours in combination with an aminoglycoside for at least 6 weeks; maximum daily dose: 18 g piperacillin/day (AHA [Baltimore 2015]); based on pharmacokinetic/pharmacodynamic data for piperacillin/tazobactam, guideline dosing may be suboptimal and not achieve the desired targets needed to treat endocarditis; a higher total daily dose given more frequently (~300 mg piperacillin/kg/day divided every 6 hours) has been suggested; extended infusion (eg, infuse over 3 to 4 hours) would be needed if using every 8 hour dosing (Nichols 2016b).

Intra-abdominal infection, complicated: Infants, Children, and Adolescents: IV: 200 to 300 mg piperacillin/kg/day divided every 6 to 8 hours; maximum daily dose: 12 g piperacillin/day (IDSA [Solomkin 2010]).

Skin and soft tissue necrotizing infections: Infants, Children, and Adolescents: IV: 60 to 75 mg piperacillin/kg/dose every 6 hours (in combination with vancomycin for empiric therapy); continue until further debridement is not necessary, patient has clinically improved, and patient is afebrile for 48 to 72 hours (IDSA [Stevens 2014]).

Surgical antimicrobial prophylaxis (ASHP/IDSA [Bratzler 2013]): IV:

Infants 2 to 9 months: 80 mg piperacillin/kg within 60 minutes prior to surgical incision; may repeat in 2 hours for prolonged procedure or excessive blood loss (eg, >1,500 mL in adults).

Infants >9 months, Children, and Adolescents weighing ≤40 kg: 100 mg piperacillin/kg within 60 minutes prior to surgical incision; may repeat in 2 hours for prolonged procedure or excessive blood loss (eg, >1,500 mL in adults). Maximum dose: 3,000 mg piperacillin/dose.

Adolescents weighing >40 kg: 3,000 mg piperacillin within 60 minutes prior to surgical incision; may repeat in 2 hours for prolonged procedure or excessive blood loss (eg, >1,500 mL in adults).

Dosing: Renal Impairment: Pediatric

Infants, Children, 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): Hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose: 50 to 75 mg piperacillin/kg/dose every 12 hours

Peritoneal dialysis (PD): Peritoneal dialysis removes 21% of tazobactam and 6% of piperacillin: 50 to 75 mg piperacillin/kg/dose every 12 hours

Continuous renal replacement therapy (CRRT): 35 to 50 mg piperacillin/kg/dose every 8 hours

Dosing: Hepatic Impairment: Pediatric

No dosing adjustment required

Calculations

• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation

Use: Labeled Indications

Intra-abdominal infections: Treatment of appendicitis complicated by rupture or abscess and peritonitis caused by beta-lactamase-producing strains of Escherichia coli, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides vulgatus.

Pelvic infections: Treatment of postpartum endometriosis or pelvic inflammatory disease caused by beta-lactamase-producing strains of E. coli.

Pneumonia, community-acquired: Treatment of moderate severity community-acquired pneumonia (CAP) caused by beta-lactamase-producing strains of Haemophilus influenzae.

Pneumonia, hospital-acquired (nosocomial): Treatment of moderate to severe hospital-acquired (nosocomial) pneumonia caused by beta-lactamase-producing strains of Staphylococcus aureus and by piperacillin/tazobactam-susceptible Acinetobacter baumannii, H. influenzae, Klebsiella pneumoniae, and P. aeruginosa.

Skin and skin structure infections: Treatment of skin and skin structure infections, including cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections caused by beta-lactamase-producing strains of S. aureus.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Bite wound infection, treatment (animal or human bite)Level of Evidence [G]

Based on the Infectious Diseases Society of America (IDSA) guidelines for the diagnosis and management of skin and soft tissue infections (SSTIs), piperacillin and tazobactam is an effective and recommended treatment of animal bite wound infections.

Clinical experience supports the utility of piperacillin and tazobactam in the treatment of human bite wound infections ^Ref.

Bloodstream infection (gram-negative bacteremia)Level of Evidence [B, G]

Limited data support the use of piperacillin and tazobactam in the treatment of gram-negative bacteremia ^Ref. Clinical experience also suggests the utility of piperacillin and tazobactam in the treatment of gram-negative bacteremia ^Ref. In addition, according to the IDSA clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection, piperacillin and tazobactam is effective and recommended for the treatment of intravascular catheter-related infection caused by Pseudomonas aeruginosa.

Cystic fibrosis, severe acute pulmonary exacerbationLevel of Evidence [G]

Based on the Cystic Fibrosis Foundation's cystic fibrosis pulmonary guidelines, piperacillin and tazobactam, as part of an appropriate combination regimen (which should most often include an additional antipseudomonal agent), is effective and recommended for the treatment of Pseudomonas infection during an acute exacerbation of cystic fibrosis pulmonary disease.

Malignant (necrotizing) external otitisLevel of Evidence [C]

Clinical experience suggests the utility of piperacillin and tazobactam in the treatment of malignant (necrotizing) external otitis ^Ref.

Neutropenic fever, high-risk cancer patients (empiric therapy)Level of Evidence [G]

Based on the IDSA clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer, piperacillin and tazobactam, in combination with other agents when appropriate, is effective and recommended for the management of neutropenic fever in high-risk cancer patients (ie, ANC expected to be ≤100 cells/mm³ for >7 days, clinically unstable, or significant comorbidity).

Sepsis and septic shockLevel of Evidence [G]

Based on the Society of Critical Care Medicine international guidelines for management of sepsis and septic shock, piperacillin and tazobactam, in combination with other appropriate agents, is effective and recommended for broad-spectrum antibacterial coverage (including P. aeruginosa) in the management of sepsis and septic shock.

Urinary tract infection, complicated (including pyelonephritis)Level of Evidence [C]

Data from a multicenter, open-label, noncomparative study suggest that piperacillin and tazobactam may be beneficial for the treatment of complicated urinary tract infection, including pyelonephritis ^Ref.

Clinical experience suggests the utility of piperacillin and tazobactam in the treatment of acute complicated urinary tract infections, including pyelonephritis ^Ref.

Level of Evidence Definitions

Level of Evidence Scale

Class and Related Monographs

Penicillins

Clinical Practice Guidelines

Cystic Fibrosis:

Cystic Fibrosis Foundation, “Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations,” 2009

Diabetic Foot Infection:

IDSA, “The Diagnosis and Treatment of Diabetic Foot Infections,” 2012

Endocarditis:

AHA, Infective Endocarditis in Childhood, October 2015

Intra-abdominal Infection:

Infectious Diseases Society of America (IDSA), “Diagnosis and Management of Complicated Intra-Abdominal Infections in Adults and Children,” January 2010

Neutropenic Fever:

ASCO/IDSA, "Outpatient Management of Fever and Neutropenia in Adults Treated for Malignancy," February 2018

Opportunistic Infections:

DHHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents, October 2014 [Note: Information contained within this monograph is pending revision based on these more recent guidelines]

Pneumonia, Community-Acquired:

ATS/IDSA, "Diagnosis and Treatment of Adults with Community-acquired Pneumonia," October 2019

Pneumonia, Hospital-Acquired and Ventilator-Associated:

IDSA/ATS, "Management of Adults with Hospital-Acquired and Ventilator-Associated Pneumonia," July 2016

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014

Surgical Prophylaxis:

ASHP, “Clinical Practice Guidelines for Antimicrobial Prophylaxis in Surgery,” February 2013

Administration: IV

Administer by IV infusion over 30 minutes. For extended infusion administration (off-label method), administer over 4 hours (Shea 2009).

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered. Note: Reformulated Zosyn containing EDTA has been shown to be compatible in vitro for Y-site infusion with amikacin and gentamicin diluted in NS or D5W (applies only to specific concentrations and varies by product; consult manufacturer’s labeling). Reformulated Zosyn containing EDTA is not compatible with tobramycin.

Administration: Pediatric

Parenteral:

Intermittent IV infusion: Administer over 30 minutes

Extended IV infusion: Administration over 4 hours (Knoderer 2017; Nichols 2016a).

Some penicillins (eg, carbenicillin, ticarcillin, and piperacillin) have been shown to inactivate aminoglycosides in vitro. This has been observed to a greater extent with tobramycin and gentamicin, while amikacin has shown greater stability against inactivation. Concurrent use of these agents may pose a risk of reduced antibacterial efficacy in vivo, particularly in the setting of profound renal impairment. However, definitive clinical evidence is lacking. If combination penicillin/aminoglycoside therapy is desired in a patient with renal dysfunction, separation of doses (if feasible), and routine monitoring of aminoglycoside levels, CBC, and clinical response should be considered. Note: Reformulated Zosyn containing EDTA has been shown to be compatible in vitro for Y-site infusion with amikacin and gentamicin diluted in NS or D5W (applies only to specific concentrations and varies by product; consult manufacturer's labeling). Reformulated Zosyn containing EDTA is not compatible with tobramycin.

Dietary Considerations

Some products may contain sodium.

Storage/Stability

Vials: Store intact vials at 20°C to 25°C (68°F to 77°F). Use single-dose or bulk vials immediately after reconstitution. Discard any unused portion after 24 hours if stored at 20°C to 25°C (68°F to 77°F) or after 48 hours if stored at 2°C to 8°C (36°F to 46°F). Do not freeze vials after reconstitution. Stability in D5W or NS has been demonstrated for up to 24 hours at room temperature and up to 1 week at refrigerated temperature. Stability in an ambulatory IV infusion pump has been demonstrated for a period of 12 hours at room temperature.

Galaxy containers: Store at or below -20°C (-4°F). The thawed solution is stable for 14 days at 2°C to 8°C (36°F to 46°F) or 24 hours at 20°C to 25°C (68°F to 77°F). Do not refreeze.

Preparation for Administration: Adult

Galaxy containers: Thaw at 20°C to 25°C (68°F to 77°F) or 2°C to 8°C (36°F to 46°F). Do not thaw in microwave or by bath immersion.

Vials: Reconstitute single-dose vials with 10 mL of diluent (2.25 g vial), 15 mL of diluent (3.375 g vial), or 20 mL of diluent (4.5 g vial); further dilute in D5W or NS to a volume of 50 to 150 mL. Reconstitute pharmacy bulk vials with 152 mL of diluent to yield a concentration of piperacillin 200 mg/mL and tazobactam 25 mg/mL; transfer reconstituted solution and further dilute in D5W or NS to a volume of 50 to 150 mL. Note: If using sterile water for injection for dilution, the maximum recommended volume per dose is 50 mL for single-dose and bulk vials

Preparation for Administration: Pediatric

Parenteral:

Reconstitution:

Single-dose vials: Reconstitute 2.25 g vial with 10 mL of diluent (eg, NS, D5W, SWFI), 3.375 g vial with 15 mL of diluent (eg, NS, D5W, SWFI), or 4.5 g vial with 20 mL diluent (eg, NS, D5W, SWFI).

Pharmacy bulk vial: Reconstitute with 152 mL of diluent (NS, D5W or SWFI) to yield a concentration of piperacillin 200 mg/mL and tazobactam 25 mg/mL.

Intermittent IV infusion: Further dilute dose in D5W or NS to a volume of 50 to 150 mL for a usual final concentration of piperacillin 20 to 80 mg/mL; dilution of doses in volumes as low 25 or 37.5 mL have been used in ambulatory infusion pumps.

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat bacterial infections.

Frequently reported side effects of this drug

• Headache

• Nausea

• Diarrhea

• Constipation

• Trouble sleeping

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Bruising

• Bleeding

• Seizures

• Extra muscle movement

• Clostridium difficile (C. diff)-associated diarrhea like abdominal pain or cramps, severe diarrhea or watery stools, or bloody stools.

• Infection

• Stevens-Johnson syndrome/toxic epidermal necrolysis like red, swollen, blistered, or peeling skin (with or without fever); red or irritated eyes; or sores in mouth, throat, nose, or eyes.

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

International issues:

Contraindications

Hypersensitivity to penicillins, cephalosporins, beta-lactamase inhibitors, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactic/anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity or history of sensitivity to multiple allergens. Discontinue treatment and institute appropriate therapy if an allergic reaction occurs.

• Dermatologic effects: Serious skin reactions, including toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS), acute exanthematous pustulosis, and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. If a skin rash develops, monitor closely. Discontinue if lesions progress.

• Electrolyte abnormalities: Sodium content (2.84 mEq per gram of piperacillin) should be considered in patients requiring sodium restriction. Assess electrolytes periodically in patients with low potassium reserves, especially those receiving cytotoxic therapy or diuretics.

• Hematologic effects: Prothrombin time, platelet aggregation, and clotting time abnormalities have been reported with piperacillin and particularly in patients with renal impairment. Discontinue if thrombocytopenia or bleeding occurs. Leukopenia/neutropenia may occur; appears to be reversible and most frequently associated with prolonged administration. Assess hematologic parameters periodically, especially with prolonged (≥21 days) use.

• Nephrotoxicity: Risk of nephrotoxicity is increased when piperacillin and tazobactam is given in combination with vancomycin compared to vancomycin alone or vancomycin in combination with other beta-lactams (eg, cefepime) (Mellen 2017).

• Superinfection: 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:

• Cystic fibrosis: An increased frequency of fever and rash has been reported in patients with cystic fibrosis receiving piperacillin.

• Renal impairment: Use with caution in patients with renal impairment or in hemodialysis patients. Dosage adjustment recommended.

• Seizure disorders: Use with caution in patients with a history of seizure disorder; high levels, particularly in the presence of renal impairment, may increase risk of seizures.

Special populations:

• Critically ill patients: Use of piperacillin and tazobactam in critically ill patients may delay renal recovery as compared to other beta-lactam antibacterial drugs; consider alternative treatment options in critically ill patients. If alternative treatment options are inadequate or unavailable, closely monitor renal function.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Has not been studied exclusively in the elderly. Adjust dose for renal function.

Pregnancy Considerations

Piperacillin and tazobactam cross the placenta.

Due to pregnancy-induced physiologic changes, some pharmacokinetic properties of piperacillin/tazobactam may be altered (Bourget 1998). Piperacillin/tazobactam is approved for the treatment of postpartum gynecologic infections, including endometritis or pelvic inflammatory disease, caused by susceptible organisms.

Breast-Feeding Considerations

Piperacillin is present in breast milk; information for tazobactam is not available.

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother; however, beta-lactam antibiotics are generally considered compatible with breastfeeding when used in usual recommended doses; piperacillin/tazobactam was not specifically included within this report (WHO 2002). In general, antibiotics that are present in breast milk may cause non-dose-related modification of bowel flora. Monitor infants for GI disturbances, such as thrush and diarrhea (WHO 2002).

Lexicomp Pregnancy & Lactation, In-Depth

• Piperacillin and Tazobactam

Briggs' Drugs in Pregnancy & Lactation

• Piperacillin
• Tazobactam

Adverse Reactions

Also see Piperacillin monograph.

>10%: Gastrointestinal: Diarrhea (11%)

1% to 10%:

Cardiovascular: Phlebitis (1%), flushing (≤1%), hypotension (≤1%), thrombophlebitis (≤1%)

Central nervous system: Headache (8%), insomnia (7%), rigors (≤1%)

Dermatologic: Skin rash (4%), pruritus (3%), purpuric disease (≤1%)

Endocrine & metabolic: Hypoglycemia (≤1%)

Gastrointestinal: Constipation (8%), nausea (7%), dyspepsia (3%), vomiting (3%), abdominal pain (1%), Clostridium difficile colitis (≤1%)

Hypersensitivity: Anaphylaxis (≤1%)

Infection: Candidiasis (2%)

Local: Injection site reaction (≤1%)

Neuromuscular & skeletal: Arthralgia (≤1%), myalgia (≤1%)

Respiratory: Epistaxis (≤1%)

Miscellaneous: Fever (2%)

Frequency not defined:

Endocrine & metabolic: Decreased serum albumin, decreased serum glucose, decreased serum total protein, electrolyte disorder (increases and decreases in sodium, potassium, and calcium), hyperglycemia, hypokalemia, increased gamma-glutamyl transferase

Hematologic & oncologic: Decreased hematocrit, decreased hemoglobin, eosinophilia, leukopenia, neutropenia, positive direct Coombs test, prolonged bleeding time, prolonged partial thromboplastin time, prolonged prothrombin time, thrombocythemia, thrombocytopenia

Hepatic: Increased serum alkaline phosphatase, increased serum alanine aminotransferase, increased serum aspartate aminotransferase, increased serum bilirubin

Renal: Increased blood urea nitrogen, increased serum creatinine, renal failure syndrome

<1%, postmarketing, and/or case reports: Acute generalized exanthematous pustulosis, agranulocytosis, Clostridioides difficile associated diarrhea, delirium, drug reaction with eosinophilia and systemic symptoms, eosinophilic pneumonitis, erythema multiforme, exfoliative dermatitis, hemolytic anemia, hepatitis, hypersensitivity reaction, interstitial nephritis, jaundice, nonimmune anaphylaxis, pancytopenia, seizure, shock, Stevens-Johnson syndrome, toxic epidermal necrolysis

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Penicillin Allergy

Metabolism/Transport Effects

Refer to individual components.

Drug Interactions Open Interactions

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 D: Consider therapy modification

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 Betalactamase Inhibitors. Management: Coadministration of probenecid with amoxicillin/clavulanate is not recommended per official package labeling. Risk D: Consider therapy modification

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: Vaccination with live attenuated typhoid vaccine (Ty21a) should be avoided in patients being treated with systemic antibacterial agents. Use of this vaccine should be postponed until at least 3 days after cessation of antibacterial agents. 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

Test Interactions

Positive Coombs' [direct] test; false positive reaction for urine glucose using copper-reduction method (Clinitest); may result in false positive results with the Platelia Aspergillus enzyme immunoassay (EIA); confirm with other diagnostic methods.

Monitoring Parameters

Creatinine, BUN, CBC with differential, PT, PTT, serum electrolytes, LFTs, urinalysis; signs of bleeding; monitor for signs of anaphylaxis during first dose

Advanced Practitioners Physical Assessment/Monitoring

Assess culture and sensitivity report and patient allergy history prior to starting therapy. Obtain CBC, electrolytes, renal function tests and liver function tests periodically with prolonged therapy. Dosage adjustments needed in patients with renal impairment. Monitor for signs of anaphylaxis during first dose. Assess for effectiveness of treatment. Test for C. difficile if patient develops diarrhea.

Nursing Physical Assessment/Monitoring

Check ordered labs results and report abnormalities. Monitor closely for signs of hypersensitivity (shortness-of-breath, dyspnea, chest pain, complaints of difficulty swallowing or throat tightness, or change in vital signs). Monitor for severe or bloody diarrhea and send a specimen to the lab for C. difficile. Monitor for improvement with infection. Advise patients with diabetes about use of Clinitest (may cause false-positive test). Teach patient to report opportunistic infection and hypersensitivity reaction.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Note: 8:1 ratio of piperacillin sodium/tazobactam sodium

Infusion [premixed iso-osmotic solution] [preservative free]:

Zosyn: 2.25 g: Piperacillin 2 g and tazobactam 0.25 g (50 mL) [contains edetate disodium, sodium 128 mg (5.58 mEq)]

Zosyn: 3.375 g: Piperacillin 3 g and tazobactam 0.375 g (50 mL) [contains edetate disodium, sodium 192 mg (8.38 mEq)]

Zosyn: 4.5 g: Piperacillin 4 g and tazobactam 0.5 g (100 mL) [contains edetate disodium, sodium 256 mg (11.17 mEq)]

Injection, powder for reconstitution:

Generic: Piperacillin 2 g and tazobactam 0.25 g; piperacillin 3 g and tazobactam 0.375 g; piperacillin 4 g and tazobactam 0.5 g; piperacillin 12 g and tazobactam 1.5 g; piperacillin 36 g and tazobactam 4.5 g

Injection, powder for reconstitution [preservative free]:

Zosyn: 2.25 g: Piperacillin 2 g and tazobactam 0.25 g [contains edetate disodium, sodium 130 mg (5.68 mEq)]

Zosyn: 3.375 g: Piperacillin 3 g and tazobactam 0.375 g [contains edetate disodium, sodium 195 mg (8.52 mEq)]

Zosyn: 4.5 g: Piperacillin 4 g and tazobactam 0.5 g [contains edetate disodium, sodium 260 mg (11.36 mEq)]

Zosyn: 40.5 g: Piperacillin 36 g and tazobactam 4.5 g [contains edetate disodium, sodium 2304 mg (100.4 mEq); bulk pharmacy vial]

Generic: Piperacillin 2 g and tazobactam 0.25 g; piperacillin 3 g and tazobactam 0.375 g; piperacillin 4 g and tazobactam 0.5 g

Anatomic Therapeutic Chemical (ATC) Classification

• J01CR05

Generic Available (US)

Yes: Excludes infusion

Pricing: US

Solution (Zosyn Intravenous)

2-0.25 gm/50 mL (per mL): $0.36

3-0.375 gm/50 mL (per mL): $0.48

4-0.5 g/100 mL (per mL): $0.30

Solution (reconstituted) (Piperacillin Sod-Tazobactam So Intravenous)

2.25 (2-0.25) g (per each): $6.54 - $14.50

3.375 (3-0.375) g (per each): $6.84 - $21.76

4.5 (4-0.5) g (per each): $9.12 - $27.55

13.5 (12-1.5) g (per each): $48.75 - $58.32

40.5 (36-4.5) g (per each): $87.48 - $206.16

Solution (reconstituted) (Zosyn Intravenous)

2.25 (2-0.25) g (per each): $8.24

3.375 (3-0.375) g (per each): $12.36

4.5 (4-0.5) g (per each): $16.48

40.5 (36-4.5) g (per each): $151.20

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Piperacillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs); which in turn inhibits 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. Piperacillin exhibits time-dependent killing. Tazobactam inhibits many beta-lactamases, including staphylococcal penicillinase and Richmond-Sykes types 2, 3, 4, and 5, including extended spectrum enzymes; it has only limited activity against class 1 beta-lactamases other than class 1C types.

Pharmacodynamics/Kinetics

Note: Both AUC and peak concentrations are dose proportional.

Distribution: Well into lungs, intestinal mucosa, uterus, ovary, fallopian tube, interstitial fluid, gallbladder, and bile; penetration into CSF is low in subjects with noninflamed meninges

V_d:

Piperacillin:

Neonates and Infants <2 months: Steady state: Median: 0.42 L/kg (Cohen-Wolkowiez 2014)

Infants 2 to 5 months: Single dose: 0.37 ± 0.1 L/kg (Reed 1994)

Infants 6 months to Children <6 years: Single dose: 0.36 ± 0.1 L/kg (Reed 1994)

Children 6 to 12 years: Single dose: 0.36 ± 0.2 L/kg (Reed 1994)

Note: Critically ill children 9 months to 6 years have been shown to have higher V_d of 0.511 ± 0.366 L/kg (Cies 2014)

Adolescents and Adults: 0.243 L/kg

Protein binding: Piperacillin: ~26% to 33%; Tazobactam: 31% to 32%

Metabolism:

Piperacillin: 6% to 9% to desethyl metabolite (weak activity)

Tazobactam: ~22% to inactive metabolite

Bioavailability: IM: Piperacillin: 71%; Tazobactam: 84%

Half-life elimination:

Piperacillin:

Neonates and Infants <2 months: Median: 3.5 hours; range: 1.7 to 8.9 hours (Cohen-Wolkowiez 2014)

Infants 2 to 5 months: 1.4 ± 0.5 hours (Reed 1994)

Infants and Children 6 to 23 months: 0.9 ± 0.3 hours (Reed 1994)

Children 2 to 5 years: 0.7 ± 0.1 hours (Reed 1994)

Children 6 to 12 years: 0.7 ± 0.2 hours (Reed 1994)

Adults: 0.7 to 1.2 hours

Metabolite: 1 to 1.5 hours

Tazobactam:

Infants 2 to 5 months: 1.6 ± 0.5 hours (Reed 1994)

Infants and Children 6 to 23 months: 1 ± 0.4 hours (Reed 1994)

Children 2 to 5 years: 0.8 ± 0.2 hours (Reed 1994)

Children 6 to 12 years: 0.9 ± 0.4 hours (Reed 1994)

Adults: 0.7 to 0.9 hour

Time to peak, plasma: Immediately following completion of 30-minute infusion

Excretion: Clearance of both piperacillin and tazobactam are directly proportional to renal function

Piperacillin: Urine (68% as unchanged drug); feces (10% to 20%)

Tazobactam: Urine (80% as unchanged drug; remainder as inactive metabolite)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Half-life increases 2-fold for piperacillin and 4-fold for tazobactam in patients with CrCl <20 mL/minute.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Prolonged use of penicillins may lead to development of oral candidiasis.

Effects on Bleeding

May inhibit platelet aggregation (dose related). The clinical significance may be greater with those penicillins that are combined with a beta-lactamase inhibitor and/or with agents that have greater activity against specific enteric bacterial species.

Related Information

• Desensitization Protocols

Index Terms

Piperacillin and Tazobactam Sodium; Piperacillin Sodium and Tazobactam Sodium; Piperacillin Sodium/Tazobactam; Piperacillin/Tazobactam Sod; Tazobactam and Piperacillin

References

Abdul-Aziz MH, Sulaiman H, Mat-Nor MB, et al. Beta-Lactam Infusion in Severe Sepsis (BLISS): a prospective, two-centre, open-labelled randomised controlled trial of continuous versus intermittent beta-lactam infusion in critically ill patients with severe sepsis. Intensive Care Med. 2016;42(10):1535-1545. doi: 10.1007/s00134-015-4188-0.[PubMed 26754759]

American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds. Red Book: 2018 Report of the Committee on Infectious Diseases. 31st ed. Itasca, IL: American Academy of Pediatrics; 2018.

Aronoff GR, Bennett WM, Berns JS, et al. Drug Prescribing in Renal Failure: Dosing Guidelines for Adults and Children. 5th ed. Philadelphia, PA: American College of Physicians; 2007:61, 153.

Arzuaga A, Maynar J, Gascón AR, et al. Influence of renal function on the pharmacokinetics of piperacillin/tazobactam in intensive care unit patients during continuous venovenous hemofiltration. J Clin Pharmacol. 2005;45(2):168–176. doi:10.1177/0091270004269796.[PubMed 15647409]

Asín-Prieto E, Rodríguez-Gascón A, Trocóniz IF, et al. Population pharmacokinetics of piperacillin and tazobactam in critically ill patients undergoing continuous renal replacement therapy: application to pharmacokinetic/pharmacodynamic analysis. J Antimicrob Chemother. 2014;69(1):180-189. doi:10.1093/jac/dkt304.[PubMed 23908259]

Baddour LM, Harper M. Animal bites (dogs, cats, and other animals): evaluation and management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019a.

Baddour LM, Harper M. Human bites: evaluation and management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019b.

Baltimore RS, Gewitz M, Baddour LM, et al; American Heart Association Rheumatic Fever, Endocarditis, and Kawasaki Disease Committee of the Council on Cardiovascular Disease in the Young and the Council on Cardiovascular and Stroke Nursing. Infective endocarditis in childhood: 2015 update: a scientific statement from the American Heart Association. Circulation. 2015;132(15):1487-1515. doi: 10.1161/CIR.0000000000000298.[PubMed 26373317]

Barshak MB. Antimicrobial approach to intra-abdominal infections in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019.

Bilbao-Meseguer I, Rodríguez-Gascón A, Barrasa H, Isla A, Solinís MÁ. Augmented renal clearance in critically ill patients: a systematic review. Clin Pharmacokinet. 2018;57(9):1107-1121. doi:10.1007/s40262-018-0636-7.[PubMed 29441476]

Bourget P, Sertin A, Lesne-Hulin A, et al. Influence of Pregnancy on the Pharmacokinetic Behaviour and the Transplacental Transfer of the Piperacillin-Tazobactam Combination. Eur J Obstet Gynecol Reprod Biol. 1998;76(1):21-27.[PubMed 9481541]

Bradley JS and Nelson JD, eds. Nelson's Pediatric Antimicrobial Therapy. 25th ed. Itasca, IL: American Academy of Pediatrics; 2019.

Bratzler DW, Dellinger EP, Olsen KM, et al; American Association of Health-System Pharmacists; Infectious Diseases Society of America; Surgical Infection Society; Society for Healthcare Epidemiology of America. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Am J Health Syst Pharm. 2013;70(3):195-283.[PubMed 23327981]

Bryson HM and Brogden RN, “Piperacillin/Tazobactam. A Review of its Antibacterial Activity, Pharmacokinetic Properties, and Therapeutic Potential,” Drugs, 1994, 47(3):506-35.[PubMed 7514977]

Butterfield JM, Lodise TP, Beegle S, Rosen J, Farkas J, Pai MP. Pharmacokinetics and pharmacodynamics of extended-infusion piperacillin/tazobactam in adult patients with cystic fibrosis-related acute pulmonary exacerbations. J Antimicrob Chemother. 2014;69(1):176-179. doi: 10.1093/jac/dkt300.[PubMed 23869050]

Carrié C, Legeron R, Petit L, et al. Higher than standard dosing regimen are needed to achieve optimal antibiotic exposure in critically ill patients with augmented renal clearance receiving piperacillin-tazobactam administered by continuous infusion. J Crit Care. 2018;48:66-71. doi:10.1016/j.jcrc.2018.08.026.[PubMed 30172963]

Chotiprasitsakul D, Han JH, Cosgrove SE, et al; Antibacterial Resistance Leadership Group. Comparing the outcomes of adults with Enterobacteriaceae bacteremia receiving short-course versus prolonged-course antibiotic therapy in a multicenter, propensity score-matched cohort. Clin Infect Dis. 2018;66(2):172-177. doi: 10.1093/cid/cix767.[PubMed 29190320]

Cies JJ, Shankar V, Schlichting C, Kuti JL. Population pharmacokinetics of piperacillin/tazobactam in critically ill young children. Pediatr Infect Dis J. 2014;33(2):168-173.[PubMed 23907263]

Cohen-Wolkowiez M, Watt KM, Zhou C, et al. Developmental pharmacokinetics of piperacillin and tazobactam using plasma and dried blood spots from infants. Antimicrob Agents Chemother. 2014;58(5):2856-2865.[PubMed 24614369 ]

Cornely OA, Wicke T, Seifert H, et al. Once-daily oral levofloxacin monotherapy versus piperacillin/tazobactam three times a day: a randomized controlled multicenter trial in patients with febrile neutropenia. Int J Hematol. 2004;79(1):74-78.[PubMed 14979482]

Debruyne D, Ryckelynck JP, Hurault De Ligny B, Moulin M. Pharmacokinetics of piperacillin in patients on peritoneal dialysis with and without peritonitis. J Pharm Sci. 1990;79(2):99-102. doi:10.1002/jps.2600790204.[PubMed 2324971]

File TM. Treatment of community-acquired pneumonia in adults who require hospitalization. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 11, 2020.

Flidel-Rimon O, Friedman S, Gradstein S, et al, "Reduction in Multiresistant Nosocomial Infections in Neonates Following Substitution of Ceftazidime With Piperacillin/Tazobactam in Empiric Antibiotic Therapy," Acta Paediatr, 2003, 92(10):1205-7.[PubMed 14632339]

Flidel-Rimon O, Friedman S, Leibovitz E, et al, "The Use of Piperacillin/Tazobactam (in Association With Amikacin) in Neonatal Sepsis: Efficacy and Safety Data," Scand J Infect Dis, 2006, 38(1):36-42.[PubMed 16338836]

Flume PA, Mogayzel PJ Jr, Robinson KA, et al; Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic fibrosis pulmonary guidelines: treatment of pulmonary exacerbations. Am J Respir Crit Care Med. 2009;180(9):802-808. doi: 10.1164/rccm.200812-1845PP.[PubMed 19729669]

Freifeld AG, Bow EJ, Sepkowitz KA, et al; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56-e93. doi: 10.1093/cid/cir073.[PubMed 21258094]

Gomi H, Solomkin JS, Schlossberg D, et al. Tokyo guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):3-16. doi: 10.1002/jhbp.518.[PubMed 29090866]

Grandis JR. Malignant (necrotizing) external otitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed February 28, 2018.

Gyssens IC, Dryden M, Kujath P, et al. A randomized trial of the efficacy and safety of sequential intravenous/oral moxifloxacin monotherapy versus intravenous piperacillin/tazobactam followed by oral amoxicillin/clavulanate for complicated skin and skin structure infections. J Antimicrob Chemother. 2011;66(11):2632-2642. doi: 10.1093/jac/dkr344.[PubMed 21896561]

Hayashi Y, Roberts JA, Paterson DL, Lipman J. Pharmacokinetic evaluation of piperacillin-tazobactam. Expert Opin Drug Metab Toxicol. 2010;6(8):1017-1031. doi:10.1517/17425255.2010.506187.[PubMed 20636224]

Heintz BH, Matzke GR, Dager WE. Antimicrobial dosing concepts and recommendations for critically ill adult patients receiving continuous renal replacement therapy or intermittent hemodialysis. Pharmacotherapy. 2009;29(5):562-577.[PubMed 19397464]

Hooton TM, Gupta K. Acute complicated urinary tract infection (including pyelonephritis) in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 13, 2019.

Jamal JA, Roberts DM, Udy AA, et al. Pharmacokinetics of piperacillin in critically ill patients receiving continuous venovenous haemofiltration: A randomised controlled trial of continuous infusion versus intermittent bolus administration. Int J Antimicrob Agents. 2015;46(1):39-44. doi:10.1016/j.ijantimicag.2015.02.014.[PubMed 25881872]

Jamal JA, Udy AA, Lipman J, Roberts JA. The impact of variation in renal replacement therapy settings on piperacillin, meropenem, and vancomycin drug clearance in the critically ill: an analysis of published literature and dosing regimens*. Crit Care Med. 2014;42(7):1640-1650. doi:10.1097/CCM.0000000000000317.[PubMed 24674926]

Johnson JR, Russo TA. Acute pyelonephritis in adults [published correction appears in N Engl J Med. 2018;378(11):1069]. N Engl J Med. 2018;378(1):48-59. Review.[PubMed 29298155]

Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society [published online July 14, 2016]. Clin Infect Dis. doi: 10.1093/cid/ciw353.[PubMed 27418577]

Kanj SS, Sexton DJ. Pseudomonas aeruginosa bacteremia and endocarditis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019a.

Kanj SS. Pseudomonas aeruginosa pneumonia. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed September 13, 2019b.

Kanj SS. Principles of antimicrobial therapy of Pseudomonas aeruginosa infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019c.

Kanj SS, Sexton DJ. Pseudomonas aeruginosa skin and soft tissue infections. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019d.

Kanji S, Roberts JA, Xie J, et al. Piperacillin population pharmacokinetics in critically ill adults during sustained low-efficiency dialysis. Ann Pharmacother. 2018;52(10):965-973. doi:10.1177/1060028018773771.[PubMed 29730948]

Kim A, Sutherland CA, Kuti JL, et al. Optimal Dosing of Piperacillin-Tazobactam for the Treatment of Pseudomonas aeruginosa Infections: Prolonged or Continuous infusion. Pharmacother. 2007;27(11):1490-1497.[PubMed 17963458]

Kliegman RM, Stanton BF, St. Gemell JW III, Schor NF, Behrman. Nelson Textbook of Pediatrics. 19th ed. Philadelphia, PA: Saunders Elsevier; 2011.

Knoderer CA, Karmire LC, Andricopulos KL, Nichols KR. Extended infusion of piperacillin/tazobactam in children. J Pediatr Pharmacol Ther. 2017;22(3):212-217.[PubMed 28638304]

Lipsky BA, Berendt AR, Cornia PB, et al; Infectious Diseases Society of America. 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis. 2012;54(12):e132-e173.[PubMed 22619242]

Lodise TP Jr, Lomaestro B, Drusano GL. Piperacillin-tazobactam for Pseudomonas aeruginosa infection: clinical implications of an extended-infusion dosing strategy. Clin Infect Dis. 2007;44(3):357-363. doi: 10.1086/510590.[PubMed 17205441]

MacVane SH, Kuti JL, Nicolau DP. Prolonging β-lactam infusion: a review of the rationale and evidence, and guidance for implementation. Int J Antimicrob Agents. 2014;43(2):105-113. doi: 10.1016/j.ijantimicag.2013.10.021.[PubMed 24359838]

Mandell LA, Wunderink RG, Anzueto A, et al; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44(suppl 2):S27-S72. doi: 10.1086/511159.[PubMed 17278083]

Manley HJ, Bailie GR, Frye R, McGoldrick MD. Intermittent intravenous piperacillin pharmacokinetics in automated peritoneal dialysis patients. Perit Dial Int. 2000;20(6):686-693.[PubMed 11216560]

Mazuski JE, Tessier JM, May AK, et al. The Surgical Infection Society revised guidelines on the management of intra-abdominal infection. Surg Infect (Larchmt). 2017;(1):1-76. doi: 10.1089/sur.2016.261.[PubMed 28085573]

Mellen CK, Ryba JE, Rindone JP. Does piperacillin-tazobactam increase the risk of nephrotoxicity when used with vancomycin: a meta-analysis of observational trials. Curr Drug Saf. 2017;12(1):62-66. doi: 10.2174/1574886311666161024164859.[PubMed 27784223]

Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America [published correction appears in: Clin Infect Dis. 2010;50(7):1079 (dosage error in article text); Clin Infect Dis. 2010;50(3):457]. Clin Infect Dis. 2009;49(1):1-45. doi: 10.1086/599376.[PubMed 19489710]

Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia. An official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. Am J Respir Crit Care Med. 2019;200(7):e45-e67. doi: 10.1164/rccm.201908-1581ST.[PubMed 31573350]

Moehring R. Prolonged infusions of beta-lactam antibiotics. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019a.

Moehring R, Anderson DJ. Gram-negative bacillary bacteremia in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019b.

Nichols K, Chung EK, Knoderer CA, et al. Population pharmacokinetics and pharmacodynamics of extended-infusion piperacillin and tazobactam in critically ill children. Antimicrob Agents Chemother. 2016a;60(1):522-531.[PubMed 26552978]

Nichols KR, Israel EN, Thomas CA, Knoderer CA. Optimizing guideline-recommended antibiotic doses for pediatric infective endocarditis. Ann Pharmacother. 2016b;50(5):423-427.[PubMed 26917819]

Nowé P. Piperacillin/tazobactam in complicated urinary tract infections. Intensive Care Med. 1994;20(suppl 3):S39-S42.[PubMed 7962988]

Patel N, Scheetz MH, Drusano GL, Lodise TP. Identification of optimal renal dosage adjustments for traditional and extended-infusion piperacillin-tazobactam dosing regimens in hospitalized patients. Antimicrob Agents Chemother. 2010;54(1):460-465.[PubMed 19858253]

Pemberton JH. Acute colonic diverticulitis: Medical management. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019.

Psallidas I, Corcoran JP, Rahman NM. Management of parapneumonic effusions and empyema. Semin Respir Crit Care Med. 2014;35(6):715-722. doi: 10.1055/s-0034-1395503.[PubMed 25463162]

Reed MD, Goldfarb J, Yamashita T, et al. Single-Dose Pharmacokinetics of Piperacillin and Tazobactam in Infants and Children. Antimicrob Agents Chemother. 1994;38(12):2817-2826.[PubMed 7695268]

Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International guidelines for management of sepsis and septic shock: 2016. Crit Care Med. 2017;45(3):486-552. doi: 10.1097/CCM.0000000000002255.[PubMed 28098591]

Rhodes NJ, MacVane SH, Kuti JL, Scheetz MH. Impact of loading doses on the time to adequate predicted beta-lactam concentrations in prolonged and continuous infusion dosing schemes. Clin Infect Dis. 2014;59(6):905-907. doi:10.1093/cid/ciu402.[PubMed 24867788]

Saltoglu N, Dalkiran A, Tetiker T, et al. Piperacillin/tazobactam versus imipenem/cilastatin for severe diabetic foot infections: a prospective, randomized clinical trial in a university hospital. Clin Microbiol Infect. 2010;16(8):1252-1257. doi: 10.1111/j.1469-0691.2009.03067.x.[PubMed 19832720]

Sartelli M, Catena F, Abu-Zidan FM, et al. Management of intra-abdominal infections: recommendations by the WSES 2016 consensus conference. World J Emerg Surg. 2017;12:22. doi: 10.1186/s13017-017-0132-7.[PubMed 28484510]

Schmidt GA, Mandel J. Evaluation and management of suspected sepsis and septic shock in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019.

Shea KM, Cheatham SC, Smith DW, et al. Comparative pharmacodynamics of intermittent and prolonged infusions of piperacillin/tazobactam using Monte Carlo simulations and steady-state pharmacokinetic data from hospitalized patients. Ann Pharmacother. 2009;43(11):1747-1754.[PubMed 19809009]

Shotwell MS, Nesbitt R, Madonia PN, et al. Pharmacokinetics and pharmacodynamics of extended infusion versus short infusion piperacillin-tazobactam in critically ill patients undergoing CRRT. Clin J Am Soc Nephrol. 2016;11(8):1377-1383. doi:10.2215/CJN.10260915.

Simon RH. Cystic fibrosis: Treatment of acute pulmonary exacerbations. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 10, 2019.

Solomkin JS, Mazuski JE, Bradley JS, et al. Diagnosis and management of complicated intra-abdominal infections in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin Infect Dis. 2010;50(2):133-164.[PubMed 20034345]

Stevens DL, Bisno AL, Chambers HF, et al; Infectious Diseases Society of America. Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the Infectious Diseases Society of America [published correction appears in: Clin Infect Dis. 2015;60(9):1448]. Clin Infect Dis. 2014;59(2):e10-e52. doi: 10.1093/cid/ciu444.[PubMed 24973422]

Strange C. Parapneumonic effusion and empyema in adults. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed December 28, 2017.

Tamma PD, Turnbull AE, Milstone AM, Hsu AJ, Carroll KC, Cosgrove SE. Does the piperacillin minimum inhibitory concentration for Pseudomonas aeruginosa influence clinical outcomes of children with pseudomonal bacteremia? Clin Infect Dis. 2012;55(6):799-806. doi: 10.1093/cid/cis545.[PubMed 22696019]

Tamme K, Oselin K, Kipper K, et al. Pharmacokinetics and pharmacodynamics of piperacillin/tazobactam during high volume haemodiafiltration in patients with septic shock. Acta Anaesthesiol Scand. 2016;60(2):230-240. doi:10.1111/aas.12629.[PubMed 26830215]

Tan JS, Wishnow RM, Talan DA, Duncanson FP, Norden CW; Piperacillin/Tazobactam Skin and Skin Structure Study Group. Treatment of hospitalized patients with complicated skin and skin structure infections: double-blind, randomized, multicenter study of piperacillin-tazobactam versus ticarcillin-clavulanate. Antimicrob Agents Chemother. 1993;37(8):1580-1586.[PubMed 8215266]

Thabit AK, Grupper M, Nicolau DP, Kuti JL. Simplifying piperacillin/tazobactam dosing: pharmacodynamics of utilizing only 4.5 or 3.375 g doses for patients with normal and impaired renal function. J Pharm Pract. 2017;30(6):593-599. doi:10.1177/0897190016684453.[PubMed 29121839]

Trotman RL, Williamson JC, Shoemaker DM, Salzer WL. Antibiotic dosing in critically ill adult patients receiving continuous renal replacement therapy. Clin Infect Dis. 2005;41(8):1159-1166.[PubMed 16163635]

Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi:10.2165/11318140-000000000-00000.[PubMed 20000886]

Valtonen M, Tiula E, Takkunen O, Backman JT, Neuvonen PJ. Elimination of the piperacillin/tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure. J Antimicrob Chemother. 2001;48(6):881-885.[PubMed 11733473]

Vardakas KZ, Voulgaris GL, Maliaros A, Samonis G, Falagas ME. Prolonged versus short-term intravenous infusion of antipseudomonal β-lactams for patients with sepsis: a systematic review and meta-analysis of randomised trials. Lancet Infect Dis. 2018;18(1):108-120. doi: 10.1016/S1473-3099(17)30615-1.[PubMed 29102324]

Varghese JM, Jarrett P, Boots RJ, Kirkpatrick CM, Lipman J, Roberts JA. Pharmacokinetics of piperacillin and tazobactam in plasma and subcutaneous interstitial fluid in critically ill patients receiving continuous venovenous haemodiafiltration. Int J Antimicrob Agents. 2014;43(4):343-348. doi:10.1016/j.ijantimicag.2014.01.009.[PubMed 24612982]

Vollmer CM, Zakko SF, Afdhal NH. Treatment of acute calculous cholecystitis. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019.

Weintrob AC. Clinical manifestations, diagnosis, and management of diabetic infections of the lower extremities. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019.

Wingard JR. Treatment of neutropenic fever syndromes in adults with hematologic malignancies and hematopoietic cell transplant recipients (high-risk patients). Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed August 12, 2019.

Wise R. The efficacy and safety of piperacillin/tazobactam in the therapy of bacteraemia. J Antimicrob Chemother. 1993;31(suppl A):97-104.[PubMed 8383659]

World Health Organization (WHO). Breastfeeding and Maternal Medication, Recommendations for Drugs in the Eleventh WHO Model List of Essential Drugs. 2002.

Yahav D, Franceschini E, Koppel F, et al; Bacteremia Duration Study Group. Seven versus fourteen days of antibiotic therapy for uncomplicated gram-negative bacteremia: a non-inferiority randomized controlled trial. Clin Infect Dis. 2018 December. doi: 10.1093/cid/ciy1054.[PubMed 30535100]

Yamagishi Y, Terada M, Ohki E, Miura Y, Umemura T, Mikamo H. Investigation of the clinical breakpoints of piperacillin-tazobactam against infections caused by Pseudomonas aeruginosa. J Infect Chemother. 2012;18(1):127-129. doi: 10.1007/s10156-011-0285-3.[PubMed 21814800]

Yang H, Zhang C, Zhou Q, Wang Y, Chen L. Clinical outcomes with alternative dosing strategies for piperacillin/tazobactam: a systematic review and meta-analysis. PLoS One. 2015;10(1):e0116769. doi: 10.1371/journal.pone.0116769.[PubMed 25575030]

Zobell JT, Waters CD, Young DC, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis pulmonary exacerbations: II. Cephalosporins and penicillins. Pediatr Pulmonol. 2013;48(2):107-122.[PubMed 22949297]

Zosyn (piperacillin/tazobactam) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals LLC; November 2018.

Zosyn (piperacillin/tazobactam) [prescribing information]. Philadelphia, PA: Wyeth Pharmaceuticals LLC; May 2019.

Brand Names: International

Advoctam (EG); Albactam (TH); Ampito (LK); Astaz-P (TH); Aurotaz (QA); Aurotaz-P (BH); Betamycin (TW); Bizzataz (PH); Co-Tazo (TW); Curitaz 4.5 (ZW); Diapiptaz (PH); Jeita (TW); Peratam (TH); Pipercin (IE); Pipertaz (TH); Piprataz (EG); Piptabac (CR, DO, EC, GT, HN, NI, PA, SV); Piptaz (PH, VN); Pisa (LK); Plepra-T 4.5 (PH); Pletzolyn (PH); Prizma (BH, LB, QA); Pybactam (ID); Sixacin (PY); Tabaxin (KR); Tapicin (MY); Tasovak (MX); Tazam (ID); Tazar (UA); Tazepen (MT); Tazin (LK); Tazobac (CH, DE, LI); Tazobact (HR); Tazobak (LK, PH); Tazocillin (BD); Tazocilline (FR); Tazocin (AE, BG, BH, BR, CN, CO, CR, CY, CZ, DK, EC, EE, EG, GB, GT, HK, HN, HR, ID, IE, IQ, IR, IT, JO, KR, KW, LB, LI, LT, LU, LY, MT, MX, NI, OM, PA, PE, PH, PK, PL, QA, RO, SA, SE, SG, SI, SK, SV, SY, TH, TR, TW, VN, YE); Tazocin 4 EF (ZW); Tazocin EF (AU, DO, MY, NZ); Tazomax (UY); Tazonam (AR, AT, CL, PY); Tazopelin (VN); Tazopen (BD, PH); Tazoperan (KR); Tazopip (AU, IL); Tazopril (VE); Tazorex (MT); Tazosyn (BD); Tazpen (MY, SG, UA); Tebranic (TH); Victalis (CR, DO, GT, HN, NI, PA, SV); Vigocid (PH); Yanoven (LB); Zobaction (LK); Zopercin (VN); Zopertsyn (UA); Zosyn (BB, IN, JP, LI)

Last Updated 2/24/20