Tazocin is a combination of two antibiotics - piperacillin and tazobactam. It is a broad-spectrum antibiotic used to treat many gram-positive and gram-negative bacteria including beta-lactam-producing organisms and pseudomonas aeruginosa.

Indications of Tazocin (Piperacillin and tazobactam):

• Intraabdominal infections:
  • It is used to treat peritonitis brought on by beta-lactamase-producing strains of Escherichia coli, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, or Bacteroides vulgatus as well as appendicitis complicated by rupture or abscess.
• Pelvic infections:
  • It is recommended for the treatment of pelvic inflammatory illness brought on by beta-lactamase-producing strains of E. coli, postpartum endometriosis, and other conditions.
• Community-acquired Pneumonia:
  • It is used to treat moderately severe community-acquired pneumonia brought on by Haemophilus influenzae beta-lactamase-producing strains.
  • According to IDS recommendations, Pseudomonas aeruginosa- or aspiration-related community-acquired pneumonia should only be treated with piperacillin/tazobactam.
• Nosocomial Pneumonia (hospital-acquired):
  • It is indicated for moderate to severe hospital-acquired pneumonia brought on by Acinetobacter baumannii, H. influenzae, Klebsiella pneumoniae, and P. aeruginosa as well as beta-lactamase-producing strains of Staphylococcus aureus.
• Skin and skin structure infections:
  • It is helpful in treating infections of the skin and skin structures brought on by beta-lactamase-producing strains of Staphylococcus aureus, such as cellulitis, cutaneous abscesses, and ischemic/diabetic foot infections.
• Tazocin off-label uses in adults:
  • Treatment of Bite wound infection (animal or human bite)
  • Bloodstream infection caused by gram-negative bacteremia
  • Severe acute pulmonary exacerbation of Cystic fibrosis,
  • Malignant (necrotizing) otitis externa.
  • Empiric therapy in patients with Neutropenic fever (high-risk cancer patients)
  • Sepsis and septic shock
  • Skin and soft tissue necrotizing infection,
  • Surgical site infections
  • Complicated Urinary tract infection including pyelonephritis

Tazocin (Piperacillin and tazobactam) dose in adults:

Note: The amount of piperacillin and tazobactam in an adult dose is represented as a combined amount.

Infusion method: Unless specifically noted as the longer infusion method over 4 hours, it is injected over 30 minutes.

Tazocin (Piperacillin and Tazobactam) Usual dosage range:

• Traditional infusion method (over 30 minutes):
  • Mild to moderate infections:
    • 3.375 g every 6 hours intravenously
  • Severe infections:
    • 4.5 g every 6 to 8 hours.
  • For coverage of Pseudomonas aeruginosa:
    • 4.5 g every 6 hours.
  • Usual maximum dose:
    • 18 g/day.
• Extended-infusion method (off-label method):
  • 3.375 or 4.5 g every 8 hours infused over 4 hours intravenouly
  •  Note:
    • Especially when quick achievement of therapeutic drug concentrations is required, a loading dose of 3.375 to 4.5 g administered over 30 minutes is recommended (eg, sepsis).

---

Tazocin (Piperacillin and Tazobactam) Indication-specific dosing :

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Bite wound infection (animal or human bite):

• Every 6 to 8 hours, 3.375 g intravenously.
• The length of treatment for an established infection normally ranges from 5 to 14 days and is dependent on the patient, including the clinical response.
• For empiric treatment, additional coverage for methicillin-resistant Staphylococcus aureus (MRSA) may be required.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Bloodstream infection caused by gram-negative bacteremia:

Note:

• Patients with neutropenia, severe burns, sepsis, or septic shock may get piperacillin and tazobactam concurrently with a second gram-negative active as an empirical treatment for suspected gram-negative (including P. aeruginosa) bloodstream infection.
• In critical disease or to maximise exposure while treating a vulnerable organism with a high minimum inhibitory concentration, some specialists also favour the extended-infusion approach.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Community-acquired infection in the immunocompetent host:

• 3.375 g intravenous every 6 hours.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of health-care-associated infection:

(These include infections caused by catheters, infections in immunocompromised hosts, and P. aeruginosa coverage.)

• 4.5 g every 6 hours intravenously.
• Duration of therapy:
  • A treatment of one week is advised for patients with simple Enterobacteriaceae infection who respond well to antibiotic therapy.
• Note:
  • If neutropenic, continue treatment until 2 days have passed and the neutrophil count has recovered (ANC 500 cells/mm3 and rising).
  • Treatment is prescribed for 2 weeks for P. aeruginosa bacteremia in neutropenic patients.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment dose of severe acute pulmonary exacerbation of Cystic fibrosis, failure of oral therapy, or for the coverage of P. aeruginosa:

• 4.5 g intravenous every 6 hours.

Note:

It is utilised as part of a combination regimen that also contains another antipseudomonal drug. The time frame, which depends on the clinical outcome, is typically 10 days to 3 weeks or longer.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of moderate to severe Diabetic foot infection:

• 3.375 g every 6 hours intravenously or
• 4.5 g every 8 hours.
• For the treatment of P. aeruginosa infection:
  • 4.5 g every 6 hours.
• Note:
  • Unless the patient is at risk, empiric Pseudomonas coverage with this dose is typically not recommended (eg, significant water exposure, warm climate).
  • In the absence of osteomyelitis, the duration is typically 2 to 4 weeks, but it can vary depending on the patient, including the clinical response.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Intra-abdominal infection:

• Acute Cholecystitis:
  • For one day following gallbladder removal, or until clinical resolution in patients handled non-operatively, administer 3.375 or 4.5 g intravenously every 6 hours.
• Other intra-abdominal infection such as cholangitis, perforated appendix, diverticulitis, and intraabdominal abscess:
  • Every six hours, 3.375 g or 4.5 g intravenously.
  • Following effective source control, the entire length of therapy is 4 to 7 days; however, for infections treated without surgical or percutaneous intervention, a longer period of time may be required.
  • Note: Some experts prefer the longer infusion approach for individuals who are critically unwell or at risk of contracting a germ that is drug-resistant.

Note:

Save the 4.5 g dose for patients with community-acquired infections at high risk of unfavourable outcomes and/or resistance, severe community-acquired infections, or patients with these infections.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Malignant (necrotizing) otitis externa in hospitalized patients (off-label):

• Intravenous 4.5 g every 6 hours.
• Oral step-down is included in the total therapeutic time of 6 to 8 weeks.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Neutropenic fever in high-risk cancer patients (empiric therapy) (off-label):

Note:

High-risk patients are those who are anticipated to have an ANC 100 cells/mm3 for more than 7 days or an ANC 100 cells/mm3 for any anticipated duration if there are ongoing comorbidities (for example, sepsis, mucositis, significant hepatic or renal dysfunction). Some experts define high-risk patients using an ANC cutoff 500 cells/mm3.

• 4.5g intravenously every 6 to 8 hours until the neutropenia resolves (ANC 500 cells/mm3 and growing) or the typical duration for the particular infection detected, if longer than the duration for neutropenia.
• 4.5 g should be administered every 6 hours if Pseudomonas infection is a serious concern.
• Depending on the clinical state, additional drugs can be required.

---

Tazocin (Piperacillin and Tazobactam) dose in the treatment of Pneumonia:

Pneumonia obtained in the community or as part of empiric treatment for hospital patients at risk of contracting a multidrug-resistant gram-negative bacteria, such as P. aeruginosa:

• • 4.5 g intravenously given every 6 hours as a suitable mix of medications.
  • A longer course may be necessary for severe or difficult infections or infections caused by P. aeruginosa. The entire duration is for a minimum of 5 days and depends on the disease severity and response to therapy.
  • Before stopping treatment, patients should be clinically stable and afebrile for at least 48 hours.

Pneumonia brought on by a ventilator or acquired in a hospital, or as part of pathogen-specific therapy or empiric therapy for gram-negative bacteria resistant to other medications (eg, P. aeruginosa):

• • As part of a suitable combination regimen, administer 4.5 g intravenously every 6 hours.
  • Usually, a one-week course of treatment is given, however P. aeruginosa infections and severe or complicated infections may call for a longer term.
  • Note: Some professionals favour the extended-infusion approach, especially for patients who are very unwell.

Treatment of Sepsis and septic shock (broad-spectrum empiric therapy, including P.aeruginosa):

• 4.5 g intravenously every 6 hours in addition to other suitable medications
• Depending on the patient's clinical reaction, the treatment should begin within an hour of the diagnosis of sepsis or septic shock and continue for seven to ten days, if necessary. If a noninfectious cause is found, think about stopping.

---

Skin and soft tissue infection caused by P. aeruginosa:

• Intravenous 4.5 g every 6 hours.
• Depending on how well the therapy is working, the typical treatment period lasts 10 to 14 days.

---

Necrotizing Skin and soft tissue infections:

(For comprehensive coverage of gram-positive, gram-negative, and anaerobic pathogens, excluding methicillin-resistant Staphylococcus aureus):

• As part of a suitable combination treatment, 3.375 g intravenously every 6 to 8 hours.
• Continue until no more debridement is required, the patient's condition has improved, and he or she has been afebrile for 48 to 72 hours.

---

Surgical site infections, warranting expanded coverage of gram-negative and anaerobic pathogens:

• 3.375 g every 6 hours or 4.5 g every 8 hours intravenously. 
• For the treatment of P. aeruginosa infection:
  • 4.5 g every 6 hours.
  • The severity, necessity for debridement, and clinical response all affect how long it takes.

---

Treatment of complicated Urinary tract infections (including pyelonephritis):

• 3.375 g intravenously every 6 hours, or 4.5 g every 6 hours if Pseudomonas is a concern

Note:

Therapy might last anywhere from 5 to 14 days, depending on the final antibiotic chosen for the regimen. The length of the course of treatment, if piperacillin and tazobactam are used, is 10 to 14 days.

Piperacillin and tazobactam dose in children:

Note:

• Each 3.375 g vial of the combination drug Zosyn (piperacillin/tazobactam) comprises 3 g of piperacillin sodium and 0.375 g of tazobactam sodium in an 8:1 ratio.
• The piperacillin component is the basis for dosage recommendations.
• For a better pharmacodynamic profile, some facilities divide dosages every 6 hours.
• The dosage is shown in mg/kg/dose and mg/kg/day; proceed with caution.

Tazocin (Piperacillin and tazobactam) General dosing for severe infections caused by susceptible infections:

• Traditional dosing:
  • Infants <2 months:
    • Maximum daily dose: 16 g; 240–300 mg intravenous piperacillin/kg/day divided into 3–4 doses; other experts advise 80 mg piperacillin/kg/dose every 4 hours based on a pharmacokinetic study.
  • Infants ≥2 months, Children, and Adolescents:
    • Maximum daily dose: 16 g/day. 240 to 300 mg piperacillin/kg intravenous, divided into 3 to 4 doses.
• Extended infusion dosing: Limited data available:
  • Children and Adolescents:
    • Every 6 to 8 hours, an intravenous infusion of 100 mg/kg of piperacillin is administered.

---

Tazocin (Piperacillin and tazobactam) dose for the treatment of Appendicitis and/or peritonitis:

• Infants 2 to 9 months:
  • 80 mg/kg intravenously given every eight hours.
• Infants >9 months and Children weighing ≤40 kg:
  • Maximum dose: 3,000 mg of piperacillin per dose,
• Children weighing >40 kg and Adolescents:
  • given intravenously every 8 hours.

---

Tazocin (Piperacillin and tazobactam) dose in the treatment of pseudomonal lung infection in patients with Cystic fibrosis:

• Infants, Children, and Adolescents:

Note:

Numerous dosing strategies have been examined; the ideal dose relies on the disease's severity, a person's susceptibility, or their tolerance:

• • Standard dosing range:
    • In the early days of piperacillin, some people took 350 to 400 mg/kg intravenously split every four hours. Others used 240 to 400 mg piperacillin/kg intravenous divided every eight hours.
  • High dose: Limited data available:
    • Early investigations of piperacillin alone have described doses of 450 mg piperacillin/kg intravenous divided every 4 to 6 hours or 600 mg piperacillin/kg/day divided every 4 hours.
  • The usual maximum daily dose:
    • 18 to 24 g/day of piperacillin.

Note:

• Serum sickness, immune-mediated hemolytic anaemia, and bone marrow suppression are a few unfavourable effects of using piperacillin at doses greater than 600 mg/kg/day or for longer than 14 days.

---

Tazocin (Piperacillin and tazobactam) dose for the treatment of Endocarditis:

• Children and Adolescents:
  • Maximum daily dose: 240 mg piperacillin/kg intravenous divided every 8 hours when combined with an aminoglycoside for at least 6 weeks. 18 g of piperacillin each day
  • It has been advised to use a greater total daily dose that is administered more frequently (300 mg piperacillin/kg/day divided every 6 hours); a prolonged infusion would be required if employing an every 8-hour schedule.

---

Piperacillin and tazobactam (Tazocin) dose for the treatment of complicated Intra-abdominal infection:

• Infants, Children, and Adolescents:
  • Maximum daily dose: 12 g of piperacillin per day, administered intravenously in divided doses of 200 to 300 mg/kg every 6 to 8 hours.

---

Piperacillin and tazobactam (Tazocin) dose for the treatment of Skin and soft tissue necrotizing infections:

• Infants, Children, and Adolescents:
  • For initial treatment, administer 60 to 75 mg/kg of piperacillin intravenously every six hours along with vancomycin. Continue this regimen until additional debridement is not required, the patient has shown clinical improvement, and is afebrile for 48 to 72 hours.

---

Piperacillin and tazobactam dose in the treatment of Surgical antimicrobial prophylaxis:

• Infants 2 to 9 months:
  • In the hour prior to surgery, administer 80 mg/kg of piperacillin intravenously. If the procedure is lengthy or there is a significant blood loss (e.g., >1,500 mL in adults), repeat the dose in 2 hours.
• Infants >9 months, Children, and Adolescents weighing ≤40 kg:
  • Before surgery, administer 100 mg/kg of piperacillin intravenously. If the procedure takes more than an hour or there is a significant blood loss (e.g., >1,500 mL in adults), repeat the dose in 2 hours. 3,000 mg of piperacillin maximum per dose.
• Adolescents weighing >40 kg:
  • 3,000 mg of piperacillin intravenously, one hour before to surgery; repeat in two hours if the procedure is lengthy or there is a significant blood loss (e.g., >1,500 mL in adults).

Pregnancy Risk Category: B

• Piperacillin or tazobactam may cross the placenta.
• Piperacillin/tazobactam can be used to treat postpartum gynecologic infections, such as endometritis or pelvic inflammatory disease brought on by susceptible microorganisms.

Use of piperacillin or tazobactam during breastfeeding

• Piperacillin can be excreted from breast milk, but there is limited information about tazobactam.
• Although beta-lactam antibiotics are generally thought to be compatible with breastfeeding when used in usual recommended doses; piperacillin/tazobactam was not specifically included within this report, the manufacturer states that the decision to breastfeed during therapy depends on the risks/benefits of breastfeeding to the infant and the benefits of treatment to the mother.
• Breast milk antibiotics can cause non-dose-related changes in bowel flora. Therefore, infants should be monitored for GI disturbances.

Piperacillin and tazobactam (Tazocin) Dose adjustment in renal disease:

• Traditional infusion method (ie, IV infusion over 30 minutes): Manufacturer’s labeling:
  • Creatinine clearance >40 mL/minute:
    • Dosage adjustment not necessary.
  • Creatinine clearance 20 to 40 mL/minute:
    • Give 2.25 g every six hours (3.375 g every 6 hours for hospital-acquired or ventilator-associated pneumonia)
  • Creatinine clearance <20 mL/minute:
    • Give 2.25 g every eight hours (2.25 g every 6 hours for hospital-acquired or ventilator-associated pneumonia)

Note: Some clinicians suggest adjusting the dose at Creatinine clearance ≤20 mL/minute in patients receiving either traditional or extended infusion methods, particularly if treating serious gram-negative infections (empirically or definitively).

• Extended infusion method (off-label dosing):
  • Creatinine clearance ≤20 mL/minute:
    • 375 g intravenous over 4 hours every 12 hours.
  • End-stage renal disease (ESRD):
    • Intermittent hemodialysis (IHD):
      • 2.5 g intravenous every 12 hours (2.25 g every 8 hours for pneumonia contracted in a hospital or from a ventilator);
      • hemodialysis removes 30% to 40% of a piperacillin/tazobactam dose.
    • Note:
      • Dosing is based on the premise that IHD sessions are complete three times a week.
      • Administer scheduled doses after hemodialysis on dialysis days;
      • if the next regularly scheduled dose is not due right after the dialysis session, administer an additional dose of 0.75 g after the dialysis session.
    • Peritoneal dialysis (PD):
      • 2.5 g intravenous every 12 hours (2.25 g every 8 hours for pneumonia contracted in a hospital or from a ventilator);
      • peritoneal dialysis removes 6% of piperacillin and 21% of tazobactam.
  • Continuous renal replacement therapy:
    • Drug clearance is greatly influenced by flow rate, filter type, and renal replacement technique.
    • For proper dosing, it is necessary to monitor pharmacologic response, adverse drug-related events, drug concentrations in respect to target trough, and drug concentrations themselves.
    • The following suggestions should not replace clinical judgement and are simply general advice (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and limited residual renal function):
      • • CVVH: 2.5 to 3.375 g every 6 to 8 hours
        • CVVHD: 2.5 to 3.375 g every 6 hours
        • CVVHDF: 3.75 g every 6 hours

Note:

• A higher dose of 3.375 g should be considered when treating resistant pathogens (especially Pseudomonas spp); Alternative recommendations suggest a dose of 4.5 g every 8 hours.
• Some clinicians advocate dosing with PIP to alternate with PIP/TAZ, particularly in CVVH-dependent patients, to lessen this concern.   

Tazocin Dose adjustment in liver disease:

No dosage adjustment necessary.   

Common Side Effects of Piperacillin and tazobactam (Tazocin):

• Gastrointestinal:
  • Diarrhea

Rare Side Effects of Piperacillin and tazobactam (Tazocin):

• Cardiovascular:
  • Phlebitis
  • Flushing
  • Hypotension
  • Thrombophlebitis
• Central Nervous System:
  • Headache
  • Insomnia
  • Rigors
• Dermatologic:
  • Skin Rash
  • Pruritus
  • Purpuric Disease
• Endocrine & Metabolic:
  • Hypoglycemia
• Gastrointestinal:
  • Constipation
  • Nausea
  • Dyspepsia
  • Vomiting
  • Abdominal Pain
  • Clostridium Difficile Colitis
• Hypersensitivity:
  • Anaphylaxis
• Infection:
  • Candidiasis
• Local:
  • Injection Site Reaction
• Neuromuscular & Skeletal:
  • Arthralgia
  • Myalgia
• Respiratory:
  • Epistaxis
• Miscellaneous:
  • Fever

Frequency of side effects not known:

• Endocrine & Metabolic:
  • Decreased Serum Albumin
  • Decreased Serum Glucose
  • Decreased Serum Total Protein
  • Electrolyte Disorder
  • 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 Syndrom

Contraindication to Piperacillin and tazobactam (Tazocin):

Intolerance to any ingredient in the formulation, including beta-lactamase inhibitors, cephalosporins, or penicillins

Warnings and Precautions

• Anaphylactoid/ Hypersensitivity reactions
  • Piperacillin and Tazobactam can cause severe and sometimes fatal hypersensitivity reactions.
  • It is important to stop all treatment immediately and provide support management.
• Dermatologic effects
  • Acute exanthematous pustulosis, Steven Jhonson Syndrome, toxic epidermal necrolysis, and drug response with eosinophilia (DRESS), among other life-threatening complications, may necessitate stopping therapy.
• An abnormality in the electrolyte:
  • Piperacillin may cause an increase in sodium. 
  • Low potassium levels, particularly for those who are on diuretics or cytotoxic therapy, should be evaluated.
• Hematologic effects
  • Reversible neutropenia can be caused by long-term therapy.
  • It also causes hematological toxicities such as prolonged prothrombin times and clotting times or platelet aggregation.
  • This should be stopped in the event of bleeding or thrombocytopenia.
• Nephrotoxicity:
  • Combination therapy can increase the risk for nephrotoxicity by using vancomycin and vancomycin.
• Superinfection
  • Post-treatment can lead to bacterial or fungal superinfections, such as Clostridium difficile, pseudomembranous colitis, and Clostridium difficile.
• Cystic Fibrosis:
  • Cystic Fibrosis patients can experience fever and rash after receiving piperacillin.
• Renal impairment
  • Patients with kidney impairment or patients on hemodialysis will need to adjust their doses.
• Seizure disorders:
  • Pre-existing renal impairment can make seizures worse.

Piperacillin and tazobactam: Drug Interaction

Risk Factor C (Monitor therapy)
Acemetacin	May increase the serum concentration of Penicillins.
BCG Vaccine (Immunization)	Antibiotics may diminish the therapeutic effect of BCG Vaccine (Immunization).
Flucloxacillin	Flucloxacillin's serum levels may rise in response to piperacillin.
Lactobacillus and Estriol	The therapeutic effects of Lactobacillus and Estriol may be reduced by antibiotics.
Methotrexate	Penicillins may raise the level of methotrexate in the serum.
Mycophenolate	The serum levels of the active metabolite(s) of mycophenolate may drop when penicillins are used. Enterohepatic recirculation appears to be hindered, which has this impact.
Vancomycin	Piperacillin might make Vancomycin's nephrotoxic effects worse.
Vecuronium	Vecuronium's ability to suppress neuromuscular activity may be improved by piperacillin.
Vitamin K Antagonists (eg, warfarin)	The anticoagulant impact of vitamin K antagonists may be strengthened by penicillins.
Risk Factor D (Consider therapy modification)
Aminoglycosides	Aminoglycoside serum levels may be lowered by penicillins. mainly found in patients with renal impairment and extended spectrum penicillins.
Probenecid	May raise the level of betalactamase inhibitors in the serum. Management: According to the official package labelling, probenecid and amoxicillin/clavulanate coadministration is not advised.
Sodium Picosulfate	Antibiotics may reduce Sodium Picosulfate's therapeutic impact. Management: If a patient previously used or is currently using an antibiotic, think about utilising an alternative product for bowel cleansing prior to a colonoscopy.
Tetracyclines	May reduce penicillins' therapeutic efficacy.
Typhoid Vaccine	The Typhoid Vaccine's therapeutic benefits may be reduced by antibiotics. The only strain impacted is the live attenuated Ty21a strain. Treatment: Patients receiving systemic antibacterial drugs should refrain from receiving the live attenuated typhoid vaccination (Ty21a). It is recommended to wait at least 3 days following the last dose of antibacterial medication before administering this vaccine.
Risk Factor X (Avoid combination)
BCG (Intravesical)	Antibiotics may diminish the therapeutic effect of BCG (Intravesical).
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.

Monitoring parameters:

• CBC
• Clotting profile
• Serum electrolytes
• Renal function tests/BUN
• Liver function tests
• Urinalysis
• signs of bleeding
• Signs of anaphylaxis during first dose

How to administer Piperacillin and tazobactam (Tazocin)?

• It is administered intravenously for more than 30 minutes and for a longer infusion, for more than 4 hours. It has been demonstrated in vitro that several penicillins, including carbenicillin, ticarcillin, and piperacillin, inactivate aminoglycosides.
• Combination therapy with aminoglycosides such as tobramycin and gentamycin reduces the antibacterial efficacy in vivo due to the inactivation of aminoglycosides by penicillins,  especially with renal impairment.
• In the event of renal failure, penicillin/aminoglycoside therapy is required, along with routine monitoring of aminoglycoside levels, CBC, dosage separation, and clinical response.

Note:

• For Y-site infusion with gentamicin and amikacin diluted in normal saline or dextrose water, reformulated Zosyn with EDTA is compatible in vitro (according to manufacturer's labelling).
• Tobramycin and reformulated Zosyn with EDTA are incompatible.

Mechanism of action of Piperacillin and tazobactam (Tazocin):

• A penicillin-binding protein known as piperacillin binds to one or more penicillin-binding proteins.
• As a result, the final transpeptidation step in the formation of peptidoglycan in bacterial cell walls is inhibited.
• The activity of cell wall autolytic enzymes (autolysins or murein hydrolases) results in bacterial lysis.
• But cell wall construction has halted. Time-dependent killing is a property of piperacillin.
• Numerous beta-lactamases, such as Richmond-Sykes types 2 and 3, as well as staphylococcal penicillinase type 4, are inhibited by piperacillin.
• It also inhibits Richmond-Sykes types 4, and 5.
• However, it is not effective against other beta-lactamases than those of class 1C.

Notice: Dose-proportional AUC and peak concentrations can be found.

Distribution:

• Well into the lungs, intestinal mucosa, and uterus.

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
• Infants 2 to 5 months: 1.4 ± 0.5 hours
• Infants and Children 6 to 23 months: 0.9 ± 0.3 hours
• Children 2 to 5 years: 0.7 ± 0.1 hours
• Children 6 to 12 years: 0.7 ± 0.2 hours
• Adults: 0.7 to 1.2 hours
• Metabolite: 1 to 1.5 hours

Tazobactam:

• Infants 2 to 5 months: 1.6 ± 0.5 hours
• Infants and Children 6 to 23 months: 1 ± 0.4 hours
• Children 2 to 5 years: 0.8 ± 0.2 hours
• Children 6 to 12 years: 0.9 ± 0.4 hours
• Adults: 0.7 to 0.9 hour

Time to peak, plasma:

• Immediately following completion of a 30-minute infusion

Excretion: depends on renal function

• Piperacillin: Urine (68% as unchanged drug); feces (10% to 20%)
• Tazobactam: Urine (80% as unchanged drug; remainder as inactive metabolite)

International Brands of Piperacillin and tazobactam:

• Zosyn
• Advoctam
• Albactam
• Ampito
• Astaz-P
• Aurotaz
• Aurotaz-P
• Betamycin
• Co-Tazo
• Curitaz 4.5
• Jeita
• Peratam
• Pipercin
• Pipertaz
• Piprataz
• Piptabac
• Piptaz
• Pisa
• Plepra-T 4.5
• Pletzolyn
• Prizma
• Pybactam
• Sixacin
• Tabaxin
• Tapicin
• Tasovak
• Tazar
• Tazepen
• Tazin
• Tazobac
• Tazobact
• Tazobak
• Tazocillin
• Tazocilline
• Tazocin
• Tazocin 4 EF
• Tazocin EF
• Tazomax
• Tazonam
• Tazopen
• Tazoperan
• Tazopip
• Tazopril
• Tazorex
• Tazosyn
• Tazpen
• Tebranic
• Victalis
• Vigocid
• Yanoven
• Zobaction
• Zopercin
• Zopertsyn

Piperacillin/tazobactam injection Brand Names (alternative Brands) in Pakistan:

Piperacillin/tazobactam Injection 2.25 gms in Pakistan
Pip-Tazo	Regent Laboratories Ltd.
Tazop	Global Pharmaceuticals

Piperacillin/tazobactam Injection 4.5 gms in Pakistan
Mepnam	Kanel Pharmaceuticals
Pipetazo	Rotex Medica Pakistan (Pvt) Ltd
Tazocin	Pfizer Laboratories Ltd.
Tazomax	Shaf Pharma
Tazop	Global Pharmaceuticals
Tazopip	Scitech

Piperacillin/tazobactam Injection 4.5 gms in Pakistan
Pip-Tazo	Regent Laboratories Ltd.