Usage
Cefepime + Tazobactam is prescribed for moderate to severe bacterial infections, including complicated intra-abdominal infections, complicated urinary tract infections (including pyelonephritis), uncomplicated skin and skin structure infections, pneumonia (including hospital-acquired and ventilator-associated bacterial pneumonia), and as empiric therapy in febrile neutropenic patients. It is a fourth-generation cephalosporin antibiotic (Cefepime) combined with a beta-lactamase inhibitor (Tazobactam). Cefepime inhibits bacterial cell wall synthesis, leading to bacterial cell death, while Tazobactam protects Cefepime from degradation by beta-lactamase enzymes produced by certain bacteria, thus broadening its spectrum of activity.
Alternate Names
Cefepime and Tazobactam, Cefepime/Tazobactam.
Brand names: Celrim TZ, Scud, Exblifep (cefepime and enmetazobactam, a different beta-lactamase inhibitor.)
How It Works
Pharmacodynamics: Cefepime exerts bactericidal activity by binding to penicillin-binding proteins (PBPs), crucial enzymes involved in the final steps of peptidoglycan synthesis, an essential component of the bacterial cell wall. This binding inhibits cell wall formation, leading to cell lysis and death. Tazobactam, a beta-lactamase inhibitor, binds to and inactivates beta-lactamase enzymes produced by some bacteria. These enzymes would otherwise break down Cefepime, rendering it ineffective. The combination extends the antibacterial spectrum of Cefepime against organisms that produce these enzymes.
Pharmacokinetics: Cefepime is administered intravenously or intramuscularly. It is not well-absorbed orally. Following IM administration, it is almost completely absorbed. Peak plasma concentrations are reached within 1.4-1.6 hours. Cefepime exhibits linear, dose-dependent pharmacokinetics. It is approximately 20% protein-bound and has a half-life of approximately 2-2.3 hours. Cefepime is partially metabolized to N-methylpyrrolidine (NMP), which is then converted to NMP-N-oxide. It is eliminated primarily by glomerular filtration, with about 80-85% excreted unchanged in the urine. Tazobactam is administered intravenously and reaches peak serum levels rapidly. It has a shorter half-life (approximately 0.67 hours) than cefepime and is predominantly eliminated by renal clearance, though a small amount is metabolized.
Dosage
Standard Dosage
Adults:
1-2 grams every 8-12 hours via IV infusion over 30 minutes.
Children (2 months to 16 years):
40–50 mg/kg every 8-12 hours via IV infusion over 30 minutes (max 2 g/dose).
Special Cases:
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Elderly Patients: Adjust dosage based on creatinine clearance (CrCl) if CrCl is ≤60 mL/min.
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Patients with Renal Impairment: Dosage adjustments are necessary for CrCl <60 ml/min based on their creatinine clearance. See information below for specific dosage recommendations based on creatinine clearance levels.
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Patients with Hepatic Dysfunction: No dosage adjustments are typically required.
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Patients with Comorbid Conditions: Caution is advised for patients with seizures, diabetes, gastrointestinal issues (especially colitis) or any other condition that might interact.
Clinical Use Cases
Dosing is consistent with standard dosing recommendations according to indication. Duration varies based on indication and clinical response:
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Intubation/Mechanical Ventilation/ICU Use: Standard dosing based on infection type.
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Surgical Procedures: Dosage may be adjusted based on the risk of infection.
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Emergency Situations: Standard or higher dosages may be used depending on the infection’s severity.
Dosage Adjustments
CrCl >60 mL/min: 2 g every 12 hours
CrCl 30-60 mL/min: 2 g every 24 hours
CrCl 11-29 mL/min: 1 g every 24 hours
CrCl <11 mL/min: 500 mg every 24 hours
CAPD: 2 g every 48 hours
Hemodialysis: 1 g on day 1, then 500 mg every 24 hours (administer after hemodialysis)
Pediatric patients with renal impairment require dosage adjustments proportional to those recommended for adults.
Side Effects
Common Side Effects:
Diarrhea, constipation, nausea, vomiting, rash, itching, pain and/or inflammation at the injection site, headache, fever, insomnia.
Rare but Serious Side Effects:
Severe allergic reactions (including anaphylaxis), Clostridioides difficile -associated diarrhea (CDAD), encephalopathy, neurotoxicity, seizures, hepatic dysfunction (including cholestasis), renal dysfunction, toxic nephropathy, aplastic anemia, hemolytic anemia, hemorrhage, pancytopenia, positive Coombs test (without hemolysis), Stevens-Johnson syndrome, erythema multiforme, toxic epidermal necrolysis.
Long-Term Effects:
Superinfection (e.g., C. difficile infections, oral or vaginal candidiasis), antibiotic resistance.
Adverse Drug Reactions (ADR):
Anaphylaxis, severe skin reactions, seizures, C. difficile infection.
Contraindications
Hypersensitivity to cefepime, tazobactam, other cephalosporins, penicillins, or beta-lactamase inhibitors. Use with caution in patients with a history of penicillin allergy.
Drug Interactions
Aminoglycosides (increased risk of nephrotoxicity and ototoxicity), loop diuretics (increased risk of nephrotoxicity), probenecid (may decrease Cefepime elimination), warfarin and other anticoagulants, oral neomycin, live bacterial vaccines, and neuromuscular blockers. Alcohol may interact, potentially exacerbating side effects.
Pregnancy and Breastfeeding
Cefepime is excreted in breast milk in low concentrations. Exercise caution when administering to breastfeeding mothers. Cefepime + tazobactam is categorized under former FDA pregnancy category B, meaning that animal reproduction studies have not demonstrated a fetal risk, but there are no controlled studies in pregnant women, or animal studies have shown adverse effects, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester. Use only when clearly indicated and after careful risk-benefit assessment.
Drug Profile Summary
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Mechanism of Action: Cefepime inhibits bacterial cell wall synthesis; tazobactam inhibits beta-lactamases.
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Side Effects: Diarrhea, nausea, rash, injection site reactions; rarely, severe allergic reactions, CDAD, seizures.
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Contraindications: Hypersensitivity to cephalosporins, penicillins, or beta-lactamase inhibitors.
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Drug Interactions: Aminoglycosides, loop diuretics, probenecid.
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Pregnancy & Breastfeeding: Use with caution. Category B.
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Dosage: Adults: 1-2 g IV q8-12h; Children: 40-50 mg/kg IV q8-12h. Adjust for renal impairment.
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Monitoring Parameters: Renal function, signs of hypersensitivity, superinfection.
Popular Combinations
Cefepime/tazobactam is often used as a standalone therapy.
Precautions
- General Precautions: Evaluate renal and hepatic function, history of allergies (especially to beta-lactams), and potential drug interactions before initiating therapy.
- Specific Precautions: Pregnancy (use with caution), breastfeeding (excreted in breast milk), elderly (adjust dose based on renal function), hepatic or renal impairment. Monitor for C. difficile infection with prolonged use.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Cefepime + Tazobactum?
A: Adults: 1-2 g IV every 8-12 hours; children: 40-50 mg/kg IV every 8-12 hours. Adjust dosage for renal impairment.
Q2: How is Cefepime + Tazobactum administered?
A: Intravenous infusion over 30 minutes or Deep IM injection.
Q3: What are the common side effects?
A: Diarrhea, nausea, vomiting, rash, and injection site reactions.
Q4: What are the serious side effects?
A: Allergic reactions (including anaphylaxis), C. difficile-associated diarrhea, seizures.
Q5: What are the contraindications?
A: Hypersensitivity to cephalosporins, penicillins, or beta-lactamase inhibitors.
Q6: What are the key drug interactions?
A: Aminoglycosides, loop diuretics, probenecid.
Q7: Can it be used during pregnancy and breastfeeding?
A: Use with caution; weigh the risks and benefits. Former pregnancy category B. Excreted in breast milk.
Q8: What should be monitored during therapy?
A: Renal function, signs of hypersensitivity or superinfection (e.g. C. difficile infection).
A: Complicated intra-abdominal infections, complicated urinary tract infections, uncomplicated skin infections, community and hospital acquired pneumonias, febrile neutropenia.
Q10: How does Tazobactam enhance Cefepime’s activity?
A: It inhibits bacterial beta-lactamase, which would otherwise degrade Cefepime.
