Zosyn

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Zosyn

Classes

Penicillin and Beta-Lactamase Inhibitor Combination Antibiotics

Administration
Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Piperacillin; tazobactam 2.25 g corresponds to 2 g piperacillin and 0.25 g tazobactam.
Piperacillin; tazobactam 3.375 g corresponds to 3 g piperacillin and 0.375 g tazobactam.
Piperacillin; tazobactam 4.5 g corresponds to 4 g piperacillin and 0.5 g tazobactam.

Intravenous Administration

Intravenous (IV) Infusion
Powder Vials for Injection
Reconstitution
Reconstitute with the appropriate volume of a compatible IV solution to a concentration of 202.5 mg/mL (180 mg/mL piperacillin and 22.5 mg/mL tazobactam):
Reconstitute the 2.25 g (2 g piperacillin and 0.25 g tazobactam) vial with 10 mL of a compatible IV solution.
Reconstitute the 3.375 g (3 g piperacillin and 0.375 g tazobactam) vial with 15 mL of a compatible IV solution.
Reconstitute the 4.5 g (4 g piperacillin and 0.5 g tazobactam) vial with 20 mL of a compatible IV solution.
Compatible IV solutions include 0.9% Sodium Chloride Injection, Sterile Water for Injection, 5% Dextrose Injection, Bacteriostatic Water/Parabens for Injection, Bacteriostatic Saline/Benzyl Alcohol for Injection, and Bacteriostatic Water/Benzyl Alcohol for Injection.
Swirl vial until the powder is fully dissolved.
Further dilution is necessary.
Storage: Reconstituted vials should be used immediately. Discard any unused portion after 24 hours if stored at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or after 48 hours if refrigerated (2 to 8 degrees C or 36 to 46 degrees F).[44289]
 
Dilution
For patients weighing more than 40 kg, reconstituted vials should be further diluted in 50 to 150 mL of a compatible IV solution.
For patients weighing 40 kg or less, calculate the required volume (mL) of reconstituted solution based on the required dose. Aseptically withdraw the required volume of the reconstituted solution and further dilute to a final piperacillin concentration of 20 to 80 mg/mL (tazobactam concentration of 2.5 to 10 mg/mL) in a compatible IV solution in an appropriately sized syringe or IV bag.
Compatible IV solutions include 0.9% Sodium Chloride Injection, Dextran 6% in Saline Injection, and 5% Dextrose Injection.
Lactated Ringer's Injection is ONLY compatible with piperacillin; tazobactam containing edetate disodium dihydrate (EDTA).
If Sterile Water for Injection is used as the diluent, do not exceed a maximum final volume of 50 mL.
Storage: Diluted solutions in IV glass or plastic containers are stable for up to 24 hours at room temperature and up to one week under refrigeration.[44289]
 
Bulk Vials for Injection
Reconstitution
Reconstitute pharmacy bulk vials with 152 mL of a compatible IV solution to a concentration of 225 mg/mL (200 mg/mL piperacillin and 25 mg/mL tazobactam).
Compatible IV solutions include 0.9% Sodium Chloride Injection, Sterile Water for Injection, 5% Dextrose Injection, Bacteriostatic Water/Parabens for Injection, Bacteriostatic Saline/Benzyl Alcohol for Injection, and Bacteriostatic Water/Benzyl Alcohol for Injection.
Swirl vial until the powder is fully dissolved.
After reconstitution, entry into the vial must be made with a sterile dispensing device. Use the entire contents of the vial promptly.
Further dilution is necessary
Storage: Reconstituted vials should be used immediately. Discard any unused portion after 24 hours if stored at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or after 48 hours if refrigerated (2 to 8 degrees C or 36 to 46 degrees F). Do not freeze reconstituted vials.[44289]
 
Dilution
For patients weighing more than 40 kg, reconstituted vials should be further diluted in 50 to 150 mL of a compatible IV solution.
For patients weighing 40 kg or less, calculate the required volume (mL) of reconstituted solution based on the required dose. Aseptically withdraw the required volume of the reconstituted solution and further dilute to a final piperacillin concentration of 20 to 80 mg/mL (tazobactam concentration of 2.5 to 10 mg/mL) in a compatible IV solution in an appropriately sized syringe or IV bag.
Compatible IV solutions include 0.9% Sodium Chloride Injection, Dextran 6% in Saline Injection, and 5% Dextrose Injection.
Lactated Ringer's Injection is ONLY compatible with piperacillin; tazobactam containing edetate disodium dihydrate (EDTA).
If Sterile Water for Injection is used as the diluent, do not exceed a maximum final volume of 50 mL.
Storage: Diluted solutions in IV glass or plastic containers are stable for up to 24 hours at room temperature and up to one week under refrigeration.[44289]
 
Frozen Pre-mixed Bags
Use is not recommended for doses other than 2.25 g (2 g piperacillin and 0.25 g tazobactam), 3.375 g (3 g piperacillin and 0.375 g tazobactam), or 4.5 g (4 g piperacillin and 0.5 g tazobactam); consider alternative formulations.
Handle frozen product containers with care as they may be fragile in the frozen state.
Thaw frozen containers at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or under refrigeration (2 to 8 degrees C or 36 to 46 degrees F).
Do not force thaw by immersion in water baths or by microwave irradiation.
Check for leaks by squeezing the bag firmly.
Do not add supplementary medication.
Contents of the solution may precipitate in the frozen state and should dissolve with little or no agitation once the solution has reached room temperature.
Storage: The thawed solution is stable for 24 hours at room temperature (20 to 25 degrees C or 68 to 77 degrees F) or for 14 days under refrigeration (2 to 8 degrees C or 36 to 46 degrees F). Do not refreeze thawed product.
 
Intermittent IV Infusion
Infuse IV over at least 30 minutes.
Do not use plastic containers in series connections as this could result in an embolism due to residual air being drawn from the primary container before administration of the fluid from the secondary container is complete. [44289]
 
Ambulatory IV Infusion
Piperacillin; tazobactam reconstituted and diluted from single-use and bulk vials can be used in ambulatory intravenous infusion pumps.
Doses diluted to a final volume of 37.5 mL or 25 mL have been shown to be stable for 12 hours at room temperature in medication reservoirs that were fitted into preprogrammed ambulatory IV infusion pumps.[44289]
 
Intravenous (IV) Push†
NOTE: Piperacillin; tazobactam is not approved by the FDA for IV push administration.[44289]
Powder Vials for Injection
Reconstitution
A study included 65 adult patients who received a total of 704 doses of IV push piperacillin; tazobactam in the emergency department and acute care hospital units.
Doses of 2.25 g (2 g piperacillin and 0.25 g tazobactam), 3.375 g (3 g piperacillin and 0.375 g tazobactam), and 4.5 g (4 g piperacillin and 0.5 g tazobactam) were reconstituted with 20 mL of Sterile Water for Injection.
A study assessed 300 adult patients (out of a total of 1,813 patients) who received a dose of IV push piperacillin; tazobactam in the emergency department.
Doses of 3.375 g (3 g piperacillin and 0.375 g tazobactam) were reconstituted in 10 mL of 0.9% Sodium Chloride Injection and 4.5 g (4 g piperacillin and 0.5 g tazobactam) were reconstituted with 20 mL of 0.9% Sodium Chloride Injection.
 
Intermittent IV Push
Doses of 2.25 g (2 g piperacillin and 0.25 g tazobactam), 3.375 g (3 g piperacillin and 0.375 g tazobactam), and 4.5 g (4 g piperacillin and 0.5 g tazobactam) that were reconstituted with 20 mL of Sterile Water for Injection were administered IVP at a rate of 3 to 5 minutes.
Doses of 3.375 g (3 g piperacillin and 0.375 g tazobactam) that were reconstituted in 10 mL of 0.9% Sodium Chloride Injection and doses 4.5 g (4 g piperacillin and 0.5 g tazobactam) that were reconstituted with 20 mL of 0.9% Sodium Chloride Injection were administered IVP at a rate of 2 to 3 minutes.

Adverse Reactions
Severe

anaphylactic shock / Rapid / 0-1.0
anaphylactoid reactions / Rapid / 0-1.0
renal failure (unspecified) / Delayed / 0-1.0
angioedema / Rapid / Incidence not known
erythema multiforme / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
seizures / Delayed / Incidence not known
agranulocytosis / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
pancytopenia / Delayed / Incidence not known
C. difficile-associated diarrhea / Delayed / Incidence not known
interstitial nephritis / Delayed / Incidence not known
eosinophilic pneumonia / Delayed / Incidence not known
hemophagocytic lymphohistiocytosis / Delayed / Incidence not known

Moderate

constipation / Delayed / 7.7-8.4
bullous rash / Early / 3.9-4.2
candidiasis / Delayed / 1.6-3.9
thrombocytosis / Delayed / 1.4-1.4
elevated hepatic enzymes / Delayed / 0-1.4
hypotension / Rapid / 0-1.3
phlebitis / Rapid / 0-1.3
stomatitis / Delayed / 0-1.0
hypokalemia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
anemia / Delayed / 0-1.0
eosinophilia / Delayed / 0-1.0
pseudomembranous colitis / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
delirium / Early / Incidence not known
hypernatremia / Delayed / Incidence not known
bleeding / Early / Incidence not known
leukopenia / Delayed / Incidence not known
platelet dysfunction / Delayed / Incidence not known
neutropenia / Delayed / Incidence not known
prolonged bleeding time / Delayed / Incidence not known
superinfection / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known

Mild

diarrhea / Early / 11.3-20.0
headache / Early / 4.5-7.7
nausea / Early / 5.8-6.9
insomnia / Early / 4.5-6.6
maculopapular rash / Early / 3.9-4.2
urticaria / Rapid / 3.9-4.2
rash / Early / 3.9-4.2
vomiting / Early / 2.7-3.3
dyspepsia / Early / 1.9-3.3
fever / Early / 2.4-3.2
pruritus / Rapid / 3.1-3.2
abdominal pain / Early / 1.3-1.8
flushing / Rapid / 0-1.0
injection site reaction / Rapid / 0-1.0
purpura / Delayed / 0-1.0
epistaxis / Delayed / 0-1.0
myalgia / Early / 0-1.0
arthralgia / Delayed / 0-1.0

Common Brand Names

Zosyn, Zosyn Powder

Dea Class

Rx

Description

Extended-spectrum IV penicillin/beta-lactamase inhibitor combination antibiotic
Used for nosocomial and polymicrobial infections, including intra-abdominal, skin and soft-tissue, and lower respiratory tract infections
Combination does not have any more activity against P. aeruginosa than does piperacillin alone

Dosage And Indications
For the treatment of skin and skin structure infections, including cellulitis, erysipelas, skin abscesses, necrotizing infections, animal bite wounds, diabetic foot ulcer, leg ulcer, pyomyositis, and surgical incision site infections. For the treatment of nonpurulent skin infections, such as cellulitis and erysipelas, using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 to 8 hours for 5 to 14 days.

Infants†, Children†, and Adolescents†

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) (Max: 3 g/dose piperacillin [3.375 g/dose piperacillin; tazobactam]) IV divided every 6 to 8 hours for 5 to 14 days.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 5 to 14 days.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours for 5 to 14 days.

For the treatment of diabetic foot ulcer using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours for 7 to 14 days for moderate or severe infections in patients with recent antibiotic exposure, ischemic limb/necrotizing/gas forming infections, or a macerated ulcer or in a warm climate. Continue treatment for up to 28 days if infection is improving but is extensive and resolving slower than expected or if patient has severe peripheral artery disease.

For the treatment of surgical incision site infections using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours for incisional surgical site infections of the intestinal or genitourinary tract.[57437]

For the treatment of necrotizing infections of the skin, fascia, and muscle using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus vancomycin for mixed necrotizing infections.

Infants†, Children†, and Adolescents†

60 to 75 mg/kg/dose piperacillin component (67.5 to 84 mg/kg/dose piperacillin; tazobactam) (Max: 3 g/dose piperacillin [3.375 g/dose piperacillin; tazobactam]) IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus vancomycin for mixed necrotizing infections.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus vancomycin for mixed necrotizing infections.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours until further debridement is not necessary, the patient has improved clinically, and fever has been absent for 48 to 72 hours plus vancomycin for mixed necrotizing infections.

For the treatment of animal bite wounds using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 to 8 hours. In setting of a cat or dog bite, preemptive early antimicrobial therapy for 3 to 5 days is recommended for patients who are immunocompromised, asplenic, have advanced liver disease, have edema of the bite area, have moderate to severe injuries, particularly of the hand or face, or have penetrating injuries to the periosteum or joint capsule.

For the treatment of skin and skin structure infections using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of skin and skin structure infections using continuous infusion dosing†. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion.   

For the treatment of purulent skin infections, such as skin abscesses, using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 to 8 hours for 5 to 10 days plus incision and drainage.

Infants†, Children†, and Adolescents†

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) (Max: 3 g/dose piperacillin [3.375 g/dose piperacillin; tazobactam]) IV divided every 6 to 8 hours for 5 to 10 days plus incision and drainage.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 5 to 10 days plus incision and drainage.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours for 5 to 10 days plus incision and drainage.

For the treatment of leg ulcer using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours for 7 days.

For the treatment of pyomyositis using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 to 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

Infants†, Children†, and Adolescents†

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) (Max: 3 g/dose piperacillin [3.375 g/dose piperacillin; tazobactam]) IV divided every 6 to 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours for 14 to 21 days plus vancomycin in patients with underlying conditions.

For the treatment of moderate to severe infections including pelvic inflammatory disease (PID) and endometritis. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours for 7 to 10 days. Guidelines do not include piperacillin; tazobactam for use in PID.

For the treatment of intraabdominal infections, including peritonitis, appendicitis, intraabdominal abscess, biliary tract infections (cholecystitis, cholangitis), spontaneous bacterial peritonitis†, and peritoneal dialysis-related peritonitis†. For the treatment of complicated community-acquired intraabdominal infections with adequate source control using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 4 to 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

Infants, Children, and Adolescents 2 months to 17 years

200 to 300 mg/kg/day piperacillin component (225 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

Infants younger than 2 months†

200 to 300 mg/kg/day piperacillin component (225 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours for 3 to 7 days. Complicated infections include peritonitis and appendicitis complicated by rupture, and intraabdominal abscess.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 7 to 10 days.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours for 7 to 10 days.

For the treatment of pediatric patients with intraabdominal infections using extended-infusion dosing†. Intravenous dosage Infants, Children, and Adolescents

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) administered over 4 hours IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) based on limited data.

For the treatment of adult patients with intraabdominal infections using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of adult patients with intraabdominal infections using continuous infusion dosing†. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion.[62002] [62003] [64955] [64959] [64960] [64961]

For the treatment of peritoneal dialysis-related peritonitis†. Continuous Intraperitoneal dosage† Adults

4.5 g/L (4 g piperacillin and 0.5 g tazobactam) intraperitoneal loading dose, followed by 1.125 g/L (1 g piperacillin and 0.125 g tazobactam) in each dialysate exchange. Treat for 21 to 28 days.

For the treatment of uncomplicated intraabdominal infections using conventional dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 4 to 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

Infants, Children, and Adolescents 2 months to 17 years

200 to 300 mg/kg/day piperacillin component (225 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]). Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

Infants younger than 2 months†

200 to 300 mg/kg/day piperacillin component (225 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours. Antibiotics should be discontinued within 24 hours. Uncomplicated infections include acute appendicitis without perforation, abscess, or local peritonitis; traumatic bowel perforations repaired within 12 hours; acute cholecystitis without perforation; and ischemic, non-perforated bowel.

For the treatment of spontaneous bacterial peritonitis†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours for at least 5 to 7 days.

For the treatment of community-acquired pneumonia (CAP), nosocomial pneumonia, and pleural empyema†. For the treatment of nosocomial pneumonia using conventional dosing. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours for 7 days as a singular agent or as part of combination therapy.[44289] [61215] The FDA-approved duration is 7 to 14 days.[44289]

Children and Adolescents weighing more than 40 kg

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours for 7 to 14 days. For patients with Pseudomonas pneumonia, add an aminoglycoside.

Children and Adolescents weighing 40 kg or less

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 6 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for 7 to 14 days. For patients with Pseudomonas pneumonia, add an aminoglycoside.

Infants 10 to 11 months

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 7 to 14 days. For patients with Pseudomonas pneumonia, add an aminoglycoside.

Infants 2 to 9 months

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours for 7 to 14 days. For patients with Pseudomonas pneumonia, add an aminoglycoside.

Infants younger than 2 months†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours.

For the treatment of pediatric patients with pneumonia using extended-infusion dosing†. Intravenous dosage Infants, Children, and Adolescents

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) administered over 4 hours IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) based on limited data.

For the treatment of community-acquired pneumonia (CAP) using conventional dosing. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours for at least 7 days as part of combination therapy. [64669] The FDA-approved dosage is 3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours for 7 to 10 days.[44289]

Infants†, Children†, and Adolescents† 4 months to 17 years

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]). Treat for up to 10 days depending on severity of illness and causative organism.[46963]

Infants 1 to 3 months†

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours.

Neonates older than 30 weeks postmenstrual age†

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours.

Neonates 30 weeks postmenstrual age and younger†

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours.

For the treatment of adult patients with pneumonia using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of adult patients with pneumonia using continuous infusion dosing†. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion.   

For the treatment of hospital-acquired or postprocedural pleural empyema† using conventional dosing. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours.[44289] Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.[61949]

Infants, Children, and Adolescents


240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]). Use in combination with vancomycin for at least 2 weeks after drainage and defervescence.[61949]

For the treatment of pyelonephritis†, complicated urinary tract infection (UTI)†, and catheter-associated urinary tract infection†. For the treatment of pyelonephritis and complicated UTI using conventional dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours for 7 to 14 days with or without and aminoglycoside.[49880] [64966]

Infants, Children, and Adolescents

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]). Treat for 48 to 72 hours or until patient is clinically stable and afebrile, followed by oral antibiotics for a total duration of 7 to 14 days.

For the treatment of UTI using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours for 7 to 14 days. [57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of UTI using continuous infusion dosing†. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion for 7 to 14 days. [62002] [62003] [64955] [64959] [64960] [64961]

For the treatment of catheter-associated UTI using conventional dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours for 7 to 14 days.

Infants, Children, and Adolescents

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for 7 to 14 days.

For surgical infection prophylaxis† for patients undergoing liver transplantation. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV once within 60 minutes before surgical incision, and redose during surgery every 2 hours from the initiation of the preoperative dose. The duration of prophylaxis should not exceed 24 hours.

Children and Adolescents weighing more than 40 kg

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV once within 60 minutes before surgical incision, and redose during surgery every 2 hours from the initiation of the preoperative dose. The duration of prophylaxis should not exceed 24 hours.

Infants 10 to 11 months, Children, and Adolescents weighing 40 kg or less

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV once within 60 minutes before surgical incision, and redose during surgery every 2 hours from the initiation of the preoperative dose. The duration of prophylaxis should not exceed 24 hours.

Infants 2 to 9 months

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV once within 60 minutes before surgical incision, and redose during surgery every 2 hours from the initiation of the preoperative dose. The duration of prophylaxis should not exceed 24 hours.

For the treatment of acute pulmonary exacerbations in patients with cystic fibrosis†. For acute pulmonary exacerbations in patients with cystic fibrosis using conventional dosing. Intravenous dosage Adults

4.5 g/dose (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours is recommended by the UK CF Trust Working Group. Higher doses of 4.5 g/dose (4 g piperacillin and 0.5 g tazobactam) IV every 4 hours may be warranted.

Infants, Children, and Adolescents

80 to 100 mg/kg/dose piperacillin component (90 to 112.5 mg/kg/dose piperacillin; tazobactam) IV every 6 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) is recommended by guidelines.[51725] [53615] However, a review of the literature suggests that higher doses of 75 to 100 mg/kg/dose piperacillin component (84 to 112.5 mg/kg/dose piperacillin; tazobactam) IV every 4 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) may be warranted based on piperacillin studies and pharmacokinetic/pharmacodynamic modeling. These higher doses may be needed to maintain adequate serum concentrations in the treatment of pseudomonal isolates with higher MICs.[53616] [57707] [58079] [58080]

For acute pulmonary exacerbations in patients with cystic fibrosis using extended-infusion dosing. Intravenous dosage Infants, Children, and Adolescents

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) administered over 4 hours IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) based on limited data.

For the treatment of bacteremia† and sepsis†. For the treatment of bacteremia and sepsis using conventional dosing†. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours. Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

Infants, Children, and Adolescents

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]). Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

Neonates older than 30 weeks postmenstrual age

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours. Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response. Neonates younger than 37 weeks gestational age were excluded from guideline scope.[64985]

Neonates 30 weeks postmenstrual age and younger

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours.

For the treatment of pediatric patients with bacteremia and sepsis using extended-infusion dosing†. Intravenous dosage Infants, Children, and Adolescents

Data are very limited. 100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) administered over 4 hours IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]).[53623] Start within 1 hour for septic shock or within 3 hours for sepsis-associated organ dysfunction without shock. Duration of therapy is not well defined and dependent on patient- and infection-specific factors. Assess patient daily for de-escalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.[64985]

For the treatment of adult patients with bacteremia and sepsis using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the treatment of adult patients with bacteremia and sepsis using continuous infusion dosing†. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion.[62002] [62003] [64955] [64959] [64960] [64961] Start within 1 hour for septic shock or within 3 hours for possible sepsis without shock. Duration of therapy is not well-defined and dependent on patient- and infection-specific factors. Assess patient daily for deescalation of antimicrobial therapy based on pathogen identification and/or adequate clinical response.

For the empiric treatment of febrile neutropenia†. For the treatment of adult patients with febrile neutropenia using conventional dosing†. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours. Guidelines suggest monotherapy with an antipseudomonal beta-lactam; other antimicrobials (aminoglycosides, fluoroquinolones, and/or vancomycin) may be added for the management of complications or when antimicrobial resistance is suspected or proven.

For the treatment of pediatric patients with febrile neutropenia using extended-infusion dosing†. Intravenous dosage Infants, Children, and Adolescents

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) administered over 4 hours IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) based on limited data.

For the treatment of pediatric patients with febrile neutropenia using conventional dosing†. Intravenous dosage Infants, Children, and Adolescents

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours (Max: 4 g/dose piperacillin component [4.5 g/dose piperacillin; tazobactam]). Piperacillin; tazobactam, an antipseudomonal penicillin, has been successfully used for the empiric treatment of febrile neutropenia in pediatric patients as monotherapy or in combination with an aminoglycoside.[53160] [53587] [53588] [53589] [53591] [53592] Guidelines for the management of fever and neutropenia in cancer patients recommend monotherapy with an antipseudomonal beta-lactam or a carbapenem as empiric treatment in high-risk patients; addition of a second gram-negative antimicrobial agent (i.e., aminoglycoside, aztreonam) is recommended for patients who are clinically unstable, when a resistant infection is suspected, or for centers with high rates of resistant pathogens.[49827] [53571]

For the treatment of adult patients with febrile neutropenia using extended-infusion dosing†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of infective endocarditis†. Intravenous dosage Children and Adolescents

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for at least 6 weeks. Piperacillin; tazobactam, in combination with an aminoglycoside, is recommended as an alternative therapy for endocarditis due to gram-negative microorganisms.

Infants

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 8 hours.

Neonates older than 30 weeks postmenstrual age

80 mg/kg/dose piperacillin component (90 mg/kg/dose piperacillin; tazobactam) IV every 6 hours.

Neonates 30 weeks postmenstrual age and younger

100 mg/kg/dose piperacillin component (112.5 mg/kg/dose piperacillin; tazobactam) IV every 8 hours.

For the treatment of chorioamnionitis† or intraamniotic infection†. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

Adolescents

3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours during the intrapartum period as an alternative. Give 1 additional dose after cesarean delivery; an additional dose is generally not needed after vaginal delivery. Other risk factors such as bacteremia or persistent postpartum fever may require additional therapy.

For the treatment bronchiectasis†. For the treatment of acute exacerbations of bronchiectasis† using conventional dosing. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours for 14 days.

Infants, Children, and Adolescents

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for 14 days.

For the eradication of first or new isolates of Pseudomonas aeruginosa in patients with bronchiectasis† using conventional dosing. Intravenous dosage Adults

4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 to 8 hours for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.

Infants, Children, and Adolescents

240 to 300 mg/kg/day piperacillin component (270 to 337.5 mg/kg/day piperacillin; tazobactam) IV divided every 6 to 8 hours (Max: 4 g/dose piperacillin [4.5 g/dose piperacillin; tazobactam]) for 14 days with or without a systemic aminoglycoside or inhaled antibiotics, followed by inhaled antibiotics for 4 to 12 weeks.

For the treatment of bronchiectasis† using extended-infusion dosing. Intravenous dosage Adults

3.375 g (3 g piperacillin and 0.375 g tazobactam) administered over 4 hours IV every 8 hours or 4.5 g (4 g piperacillin and 0.5 g tazobactam) administered over 4 hours IV every 8 hours.[57817] [61791] [61792] [61793] [61999] [62000] [64955] [64956] [64957] [64958]

For the treatment of bronchiectasis† using continuous-infusion dosing. Intravenous dosage Adults

2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g (8 g piperacillin and 1 g tazobactam) or 13.5 g (12 g piperacillin and 1.5 g tazobactam) administered over 24 hours as continuous IV infusion or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV once, then 18 g (16 g piperacillin and 2 g tazobactam) administered over 24 hours as continuous IV infusion.   

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Patients with hepatic cirrhosis experience increases in the half-lives of piperacillin and tazobactam by approximately 25% and 18%, respectively, compared to healthy subjects. However, dosage adjustments are not required.[44289]

Renal Impairment

Conventional dosing
Adult patients (FDA-labeling) [44289]
CrCl more than 40 mL/minute: No dosage adjustment needed.
CrCl 20 to 40 mL/minute: For nosocomial pneumonia, reduce dose to 3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours. For all other indications, reduce dose to 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 6 hours.
CrCl less than 20 mL/minute: For nosocomial pneumonia, reduce dose to 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 6 hours. For all other indications, reduce dose to 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 8 hours.
 
Adult patients (alternative) [32569]
CrCl more than 50 mL/minute: No dosage adjustment needed.
CrCl 20 to 50 mL/minute: For mild/moderate infections, 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 6 hours. For pseudomonal infections, 3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 6 hours, and for severe/life-threatening infections, up to 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 to 12 hours.
CrCl less than 20 mL/minute: For mild/moderate infections, 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 8 hours. For pseudomonal infections, 3.375 g (3 g piperacillin and 0.375 g tazobactam) IV every 8 hours, and for severe/life-threatening infections, up to 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 to 12 hours.
 
Pediatric patients [32569]
GFR more than 50 mL/minute/1.73 m2: No dosage adjustment needed.
GFR 30 to 50 mL/minute/1.73 m2: 35 to 50 mg/kg/dose (piperacillin component) IV every 6 hours.
GFR 29 mL/minute/1.73 m2 or less: 35 to 50 mg/kg/dose (piperacillin component) IV every 8 hours.
 
Intermittent hemodialysis
Adult patients
For nosocomial pneumonia, the maximum recommended dose is 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 8 hours; for all other indications, the maximum recommended dose is 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 12 hours. For severe/life-threatening infections, up to 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 to 12 hours may be used. Because 30% to 40% of a dose of piperacillin; tazobactam is removed during hemodialysis, administer an additional dose of 0.75 g (0.67 g piperacillin and 0.08 g tazobactam) to 1.125 g (1 g piperacillin and 0.125 g tazobactam) IV after each dialysis period.[32569] [44289]
 
Pediatric patients
50 to 75 mg/kg/dose (piperacillin component) IV every 12 hours.[32569]
 
Continuous renal replacement therapy (CRRT)
Adult patients
4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 8 hours.[32569]
 
Pediatric patients
35 to 50 mg/kg/dose (piperacillin component) IV every 8 hours.[32569]
 
Peritoneal dialysis (CAPD)
Adult patients
For nosocomial pneumonia, the maximum recommended dose is 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 8 hours; for all other indications, the maximum recommended dose is 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV every 12 hours. Alternatively, 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 12 hours may be used. No additional doses after the dialysis session are required for CAPD patients.[44289] .[32569]
 
Pediatric patients
50 to 75 mg/kg/dose (piperacillin component) IV every 12 hours.[32569]
 
Extended-infusion dosing†
The following dose adjustments are based on studies in adult patients.[57817] [61791] [61792] [61793] [61794] [61999] [62000] Consider similar adjustments for pediatric patients as specific renal dose adjustments are not available for extended-infusion dosing in pediatrics.
CrCl 20 mL/minute or more: No dosage adjustment needed.
CrCl less than 20 mL/minute: Extend dosing interval to every 12 hours.
 
Intermittent hemodialysis
Extend dosing interval to every 12 hours.[61791] [61792] [61793] [61999]
 
Continuous renal replacement therapy (CRRT)
Generally, studies have suggested administering the same dose every 8 hours for CRRT.[61791] [61792] [61793] [62001] A single study suggested maintaining the same dose every 8 to 12 hours for continuous venovenous hemofiltration (CVVH) and maintaining the same dose every 8 hours for continuous venovenous hemodialysis (CVVHD) or continuous venovenous hemodiafiltration (CVVHDF).[61999]
 
Peritoneal dialysis (CAPD)
Extend dosing interval to every 12 hours.[61791] [61999]
 
Continuous infusion dosing†
Adult patients
CrCl 40 mL/minute or more: No dosage adjustment needed.
CrCl 20 to 40 mL/minute: 2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then if the regular dose was 13.5 g/24 hours (12 g piperacillin and 1.5 g tazobactam) IV, decrease the dose to 9 g/24 hours (8 g piperacillin and 1 g tazobactam) IV. If the regular dose was 9 g/24 hours (8 g piperacillin and 1 g tazobactam) IV, no dosage adjustment needed.
CrCl less than 20 mL/minute: Excluded.[62002] [62003]
 
Continuous renal replacement therapy (CRRT)
2.25 g (2 g piperacillin and 0.25 g tazobactam) IV once, then 9 g/24 hours (8 g piperacillin and 1 g tazobactam) IV was used in patients receiving continuous venovenous hemofiltration (CVVH).[62004]

Drug Interactions

Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Acetaminophen; Aspirin; Diphenhydramine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Anticoagulants: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Antithrombin III: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Apixaban: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Argatroban: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Aspirin, ASA: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Butalbital; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Carisoprodol; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Dipyridamole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Omeprazole: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Aspirin, ASA; Oxycodone: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Atracurium: (Moderate) Concomitant use of atracurium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Betrixaban: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Bivalirudin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Butalbital; Aspirin; Caffeine; Codeine: (Minor) Due to the high protein binding of aspirin, it could displace or be displaced from binding sites by other highly protein-bound drugs, such as penicillins. Also, aspirin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. Overall, this combination should be used with caution and patients monitored for increased side effects.
Caffeine; Sodium Benzoate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Choline Salicylate; Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Cisatracurium: (Moderate) Concomitant use of cisatracurium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Dabigatran: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Dalteparin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Desirudin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Digoxin: (Minor) Displacement of penicillins from plasma protein binding sites by highly protein bound drugs like digoxin will elevate the level of free penicillin in the serum. The clinical significance of this interaction is unclear. It is recommended to monitor these patients for increased adverse effects.
Edoxaban: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Enoxaparin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Ethacrynic Acid: (Minor) Ethacrynic acid may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Fondaparinux: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Furosemide: (Minor) Furosemide may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Heparin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Indomethacin: (Minor) Indomethacin may compete with penicillin for renal tubular secretion, increasing penicillin serum concentrations. This combination should be used with caution and patients monitored for increased side effects.
Mafenide: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Magnesium Salicylate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites, or could displace other highly protein-bound drugs such as penicillins, and sulfonamides. An enhanced effect of the displaced drug may occur.
Methotrexate: (Major) Avoid concomitant use of methotrexate with penicillins due to the risk of severe methotrexate-related adverse reactions. If concomitant use is unavoidable, closely monitor for adverse reactions.
Mivacurium: (Moderate) Concomitant use of mivacurium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Oral Contraceptives: (Moderate) It would be prudent to recommend alternative or additional contraception when oral contraceptives (OCs) are used in conjunction with antibiotics. It was previously thought that antibiotics may decrease the effectiveness of OCs containing estrogens due to stimulation of metabolism or a reduction in enterohepatic circulation via changes in GI flora. One retrospective study reviewed the literature to determine the effects of oral antibiotics on the pharmacokinetics of contraceptive estrogens and progestins, and also examined clinical studies in which the incidence of pregnancy with OCs and antibiotics was reported. It was concluded that the antibiotics ampicillin, ciprofloxacin, clarithromycin, doxycycline, metronidazole, ofloxacin, roxithromycin, temafloxacin, and tetracycline did not alter plasma concentrations of OCs. Antituberculous drugs (e.g., rifampin) were the only agents associated with OC failure and pregnancy. Based on the study results, these authors recommended that back-up contraception may not be necessary if OCs are used reliably during oral antibiotic use. Another review concurred with these data, but noted that individual patients have been identified who experienced significant decreases in plasma concentrations of combined OC components and who appeared to ovulate; the agents most often associated with these changes were rifampin, tetracyclines, and penicillin derivatives. These authors concluded that because females most at risk for OC failure or noncompliance may not be easily identified and the true incidence of such events may be under-reported, and given the serious consequence of unwanted pregnancy, that recommending an additional method of contraception during short-term antibiotic use may be justified. During long-term antibiotic administration, the risk for drug interaction with OCs is less clear, but alternative or additional contraception may be advisable in selected circumstances. Data regarding progestin-only contraceptives or for newer combined contraceptive deliveries (e.g., patches, rings) are not available.
Pancuronium: (Moderate) Concomitant use of pancuronium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Pentosan: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Probenecid: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed. (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Probenecid; Colchicine: (Minor) Probenecid competitively inhibits renal tubular secretion and causes higher, prolonged serum levels of penicillins. In general, this pharmacokinetic interaction is not harmful and can be used therapeutically if needed. (Minor) Probenecid may prolong serum concentrations of tazobactam when coadministered with ceftolozane; tazobactam. Probenecid has been shown to prolong the half-life of tazobactam by 71% when coadministered. The clinical significance of this interaction has not been established.
Rivaroxaban: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Rocuronium: (Moderate) Concomitant use of rocuronium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Salsalate: (Minor) Due to high protein binding, salicylates could be displaced from binding sites or could displace other highly protein-bound drugs such as penicillins. An enhanced effect of the displaced drug may occur.
Sodium Benzoate; Sodium Phenylacetate: (Moderate) Antibiotics that undergo tubular secretion such as penicillins may compete with phenylacetlyglutamine and hippuric acid for active tubular secretion. The overall usefulness of sodium benzoate; sodium phenylacetate is due to the excretion of its metabolites. An increase in metabolite concentrations could contribute to failed treatment and worsening of the patient's clinical status. This combination should be used with caution.
Sodium picosulfate; Magnesium oxide; Anhydrous citric acid: (Major) Prior or concomitant use of antibiotics with sodium picosulfate; magnesium oxide; anhydrous citric acid may reduce efficacy of the bowel preparation as conversion of sodium picosulfate to its active metabolite bis-(p-hydroxy-phenyl)-pyridyl-2-methane (BHPM) is mediated by colonic bacteria. If possible, avoid coadministration. Certain antibiotics (i.e., tetracyclines and quinolones) may chelate with the magnesium in sodium picosulfate; magnesium oxide; anhydrous citric acid solution. Therefore, these antibiotics should be taken at least 2 hours before and not less than 6 hours after the administration of sodium picosulfate; magnesium oxide; anhydrous citric acid solution.
Sulfadiazine: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfasalazine: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Sulfonamides: (Minor) Sulfonamides may compete with piperacillin for renal tubular secretion, increasing piperacillin serum concentrations. Use this combination with caution, and monitor patients for increased side effects.
Tetracyclines: (Minor) Consider additional monitoring or alternative antimicrobial therapy for patients with infections in which clinical response is highly dependent upon the rapid, bactericidal activity of penicillins. Bacterostatic antibacterials like tetracyclines may antagonize the bactericidal effects of penicillins which may reduce their efficacy. The clinical relevance of this interaction is poorly defined and for many infections the benefits of combination therapy are likely to outweigh the potential risks.
Typhoid Vaccine: (Major) Antibiotics which possess bacterial activity against salmonella typhi organisms may interfere with the immunological response to the live typhoid vaccine. Allow 24 hours or more to elapse between the administration of the last dose of the antibiotic and the live typhoid vaccine.
Vancomycin: (Moderate) Piperacillin; tazobactam, when used concomitantly with vancomycin, may increase the risk of acute kidney injury. A limited number of retrospective studies have detected an increased incidence of acute kidney injury in patients administered concomitant piperacillin; tazobactam and vancomycin as compared to those who received vancomycin alone. Careful patient monitoring while on concurrent therapy with vancomycin is recommended.
Vecuronium: (Moderate) Concomitant use of vecuronium and piperacillin may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
Warfarin: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.

How Supplied

Piperacillin Sodium, Tazobactam Sodium/Piperacillin, Tazobactam/Zosyn/Zosyn Powder Intravenous Inj Pwd F/Sol: 2.25g, 3.375g, 4.5g, 40.5g, 12-1.5g
Zosyn Intravenous Inj Sol: 50mL, 100mL, 2-0.25g, 3-0.375g, 4-0.5g

Maximum Dosage
Adults

18 g/day (16 g piperacillin and 2 g tazobactam) IV; however, doses up to 27 g/day (24 g piperacillin and 3 g tazobactam) IV have been used off-label for patients with cystic fibrosis.

Geriatric

18 g/day (16 g piperacillin and 2 g tazobactam) IV; however, doses up to 27 g/day (24 g piperacillin and 3 g tazobactam) IV have been used off-label for patients with cystic fibrosis.

Adolescents

weighing more than 40 kg: 18 g/day (16 g piperacillin and 2 g tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam; Max: 27 g/day [24 g piperacillin and 3 g tazobactam]) IV have been used off-label for patients with cystic fibrosis.
weighing 40 kg or less: 400 mg/kg/day piperacillin component (450 mg/kg/day piperacillin; tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam) IV have been used off-label for patients with cystic fibrosis.

Children

weighing more than 40 kg: 18 g/day (16 g piperacillin and 2 g tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam; Max: 27 g/day [24 g piperacillin and 3 g tazobactam]) IV have been used off-label for patients with cystic fibrosis.
weighing 40 kg or less: 400 mg/kg/day piperacillin component (450 mg/kg/day piperacillin; tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam) IV have been used off-label for patients with cystic fibrosis.

Infants

10 to 11 months: 400 mg/kg/day piperacillin component (450 mg/kg/day piperacillin; tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam) IV have been used off-label for patients with cystic fibrosis.
2 to 9 months: 320 mg/kg/day piperacillin component (360 mg/kg/day piperacillin; tazobactam) IV is FDA-approved dosage; however, doses up to 600 mg/kg/day piperacillin component (675 mg/kg/day piperacillin; tazobactam) IV have been used off-label for patients with cystic fibrosis.
1 month: Safety and efficacy have not been established; however, doses up to 320 mg/kg/day piperacillin component (360 mg/kg/day piperacillin; tazobactam) IV have been used off-label.

Neonates

older than 30 weeks postmenstrual age: Safety and efficacy have not been established; however, doses up to 320 mg/kg/day piperacillin component (360 mg/kg/day piperacillin; tazobactam) IV have been used off-label.
30 weeks postmenstrual age and younger: Safety and efficacy have not been established; however, doses up to 300 mg/kg/day piperacillin component (337.5 mg/kg/day piperacillin; tazobactam) IV have been used off-label.

Mechanism Of Action

Piperacillin is a beta-lactam antibiotic and is mainly bactericidal. It inhibits the third and final stage of bacterial cell wall synthesis by preferentially binding to specific penicillin-binding proteins (PBPs) that are located inside the bacterial cell wall. PBPs are responsible for several steps in the synthesis of the cell wall and are found in quantities of several hundred to several thousand molecules per bacterial cell. PBPs vary among different bacterial species. Thus, the intrinsic activity of piperacillin, as well as the other penicillins, against a particular organism depends on its ability to gain access to and bind with the necessary PBP. Like all beta-lactam antibiotics, piperacillin's ability to interfere with PBP-mediated cell wall synthesis ultimately leads to cell lysis. Lysis is mediated by bacterial cell wall autolytic enzymes (i.e., autolysins). The relationship between PBPs and autolysins is unclear, but it is possible that the beta-lactam antibiotic interferes with an autolysin inhibitor.[44289] [49841]
 
Tazobactam, like sulbactam and clavulanic acid, is an irreversible inhibitor of bacterial beta-lactamases. Tazobactam protects piperacillin against Richmond and Sykes types II, III, IV, and V beta-lactamases; staphylococcal penicillinase; and extended-spectrum beta-lactamases. However, tazobactam has only species-specific activity against class I chromosomally-mediated beta-lactamases. It has little useful antibacterial activity by itself and does not alter the actions of piperacillin.[44289]
 
Beta-lactams exhibit concentration-independent or time-dependent killing. In vitro and in vivo animal studies have demonstrated that the major pharmacodynamic parameter that determines efficacy for beta-lactams is the amount of time free (non-protein bound) drug concentrations exceed the minimum inhibitory concentration (MIC) of the organism (free T above MIC).[34143] [34145] [35436] [35437] [35438] [35439] This microbiological killing pattern is due to the mechanism of action, which is acylation of PBPs. There is a maximum proportion of PBPs that can be acylated; therefore, once maximum acylation has occurred, killing rates cannot increase.[35439] Free beta-lactam concentrations do not have to remain above the MIC for the entire dosing interval. The percentage of time required for both bacteriostatic and maximal bactericidal activity is different for the various classes of beta-lactams. Penicillins require free drug concentrations to exceed the MIC for 30% of the dosing interval to achieve bacteriostatic activity and 50% of the dosing interval to achieve bactericidal activity.[35436] [35437] [35438]
 
The susceptibility interpretive criteria for piperacillin; tazobactam are delineated by pathogen. The MICs are defined for Acinetobacter sp., anaerobes, other non-Enterobacterales, Aeromonas sp., and Vibrio sp. (excluding V. cholerae) as susceptible at 16/4 mcg/mL or less, intermediate at 32/4 to 64/4 mcg/mL, and resistant at 128/4 mcg/mL or more. The Clinical and Laboratory Standards Institute (CLSI) and the FDA differ on MIC interpretation for Enterobacterales and for P. aeruginosa. The MICs are defined by the FDA for Enterobacterales as susceptible at 8/4 mcg/mL or less, intermediate at 16/4, and resistant at 32/4 mcg/mL or more; however, the MICs are defined by the CLSI as susceptible at 8/4 mcg/mL or less, susceptible dose dependent (SDD) at 16/4 mcg/mL, and resistant at 32/4 mcg/mL or more. CLSI breakpoints for susceptible are based on a dosage regimen of 3.375 g (3 g piperacillin and 0.375 g tazobactam) or 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours administered as a 30-minute infusion. CLSI breakpoints for SDD are based on a dosage regimen of 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV administered every 6 hours as a 3-hour infusion or every 8 hours as a 4-hour infusion. The MICs are defined by the FDA for P. aeruginosa as susceptible at 16/4 mcg/mL or less, intermediate at 32/4 to 64/4 mcg/mL, and resistant at 128/4 mcg/mL or more; however, the MICs are defined by the CLSI as susceptible at 16/4 mcg/mL or less, intermediate at 32/4 mcg/mL, and resistant at 64/4 mcg/mL or more [based on a dosage regimen of 4.5 g (4 g piperacillin and 0.5 g tazobactam) IV every 6 hours administered as a 30-min or 3-hour infusion]. The MICs are defined for H. influenzae and H. parainfluenzae as susceptible at 1/4 mcg/mL or less and resistant at 2/4 mcg/mL or more. Enterococci susceptible to penicillin are predictably susceptible to piperacillin; tazobactam for non-beta-lactamase producing enterococci. Considering site of infection and appropriate piperacillin; tazobactam dosing, oxacillin-susceptible staphylococci can be considered susceptible to piperacillin; tazobactam.

Pharmacokinetics

Piperacillin; tazobactam is administered intravenously as an infusion. Both piperacillin and tazobactam are approximately 30% bound to plasma protein and are unaffected by the presence of each other. Protein binding of the tazobactam metabolite is negligible. Piperacillin and tazobactam are widely distributed into tissues and body fluids including the intestinal mucosa, lung, female reproductive tissues (uterus, ovary, and fallopian tube), interstitial fluid, and bile. Mean tissue concentrations are generally 50 to 100% of those in plasma. Minimal concentrations are reached within the CSF when the meninges are uninflamed; these levels increase in the presence of inflammation. Piperacillin crosses the placenta.
 
Piperacillin is metabolized to a minor active desethyl metabolite. Tazobactam is metabolized to a single metabolite that lacks pharmacological and antibacterial activity. Both piperacillin and tazobactam are excreted into the urine primarily via tubular secretion and glomerular filtration. Approximately 68% of piperacillin and 80% of tazobactam are excreted as unchanged drug. Biliary excretion accounts for a portion of the dose, and a small percentage is excreted in breast milk. In patients with normal renal function, the elimination half-life of piperacillin and tazobactam ranges from 0.7 to 1.5 hours.

Intravenous Route

Piperacillin; tazobactam is administered intravenously as a 30-minute infusion. Peak serum concentrations of piperacillin and tazobactam are attained immediately after the completion of the infusion. Mean peak plasma concentrations of piperacillin are approximately 134, 242, and 298 mcg/ml for the 2.25 g, 3.375 g, and 4.5 g doses, respectively. Piperacillin concentrations obtained after administration of piperacillin; tazobactam are similar to those attained with equivalent doses of piperacillin alone. Steady state serum concentrations are similar to those attained after the first dose. The half-lives of piperacillin and tazobactam were unaffected by dose or duration of infusion.

Pregnancy And Lactation
Pregnancy

Piperacillin and tazobactam cross the placenta in humans. However, there are insufficient data with piperacillin and/or tazobactam in human pregnancy to inform a drug-associated risk for major birth defects and miscarriage. No fetal structural abnormalities were observed in rats or mice when piperacillin; tazobactam was given intravenously at doses 1 to 2 times and 2 to 3 times the human doses of piperacillin and tazobactam, respectively, based on body surface area. Fetotoxicity (i.e., increased stillbirths, increased pup mortality) in the presence of maternal toxicity was observed in peri/postnatal studies in rats given piperacillin; tazobactam by intraperitoneal administration prior to mating and throughout gestation or from gestation day 17 through lactation day 21 at doses less than the maximum recommended human daily dose based on body surface area.

Piperacillin is excreted in human breast milk; tazobactam concentrations in human milk have not been studied. There is no available information on the effects of piperacillin or tazobactam on the breast-fed child or on milk production. Penicillins may cause diarrhea (due to disruption of GI flora), candidiasis, and skin rash in the breast-feeding infant. Unless the infant is allergic to penicillins, breast-feeding is generally safe during maternal penicillin therapy; observe the infant for potential effects. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for piperacillin; tazobactam and any potential adverse effects on the breast-fed child from piperacillin; tazobactam or the underlying maternal condition.