What is the spectrum of activity and recommended dose of Cefepime (Cefepime) and Tazobactam (Tazobactam)?

From the Guidelines

Cefepime-tazobactam is a broad-spectrum antibiotic combination with a typical adult dose of 2g/1g administered intravenously every 8 hours, as recommended for severe infections, with adjustments required for patients with renal impairment. The spectrum of cefepime-tazobactam includes gram-positive, gram-negative, and anaerobic bacteria, including many extended-spectrum beta-lactamase (ESBL) producers, such as Pseudomonas aeruginosa, Enterobacteriaceae, Streptococcus species, and some anaerobes 1. This combination is particularly useful for complicated intra-abdominal infections, complicated urinary tract infections, hospital-acquired pneumonia, and empiric therapy for febrile neutropenia.

Key Points

• The combination provides enhanced coverage compared to cefepime alone due to tazobactam's beta-lactamase inhibition, which protects cefepime from enzymatic degradation.
• Common side effects include gastrointestinal disturbances, rash, and potential for C. difficile-associated diarrhea.
• Monitoring renal function during therapy is important, especially in critically ill patients or those with baseline renal impairment, as recommended by guidelines for the management of intra-abdominal infections 1 and hospital-acquired pneumonia 1.
• The dosage may need to be adjusted based on renal function, with consideration of the patient's creatinine clearance and weight, as suggested in the guidelines for hospital-acquired pneumonia 1.

Clinical Use

Cefepime-tazobactam is a valuable option for empiric therapy in critically ill patients, including those with suspected ventilator-associated pneumonia, where broad-spectrum coverage is essential, as outlined in the guidelines for hospital-acquired pneumonia 1. However, it is crucial to consider local antimicrobial resistance patterns and adjust the treatment regimen accordingly, as recommended by the guidelines for intra-abdominal infections 1.

Dosing Considerations

The recommended dose of cefepime-tazobactam is 2g/1g administered intravenously every 8 hours, with adjustments for renal impairment, as suggested in the guidelines for intra-abdominal infections 1 and hospital-acquired pneumonia 1. Extended infusions may be appropriate in certain cases, such as in patients with severe infections or those at risk of antibiotic resistance, as recommended by the guidelines for hospital-acquired pneumonia 1.

From the FDA Drug Label

Cefepime has a broad spectrum of in vitro activity that encompasses a wide range of Gram-positive and Gram-negative bacteria. Cefepime has been shown to be active against most isolates of the following microorganisms, both in vitro and in clinical infections as described in the INDICATIONS AND USAGE section. Gram-negative bacteria Enterobacter spp Escherichia coli Klebsiella pneumoniae Proteus mirabilis Pseudomonas aeruginosa Gram-positive bacteria Staphylococcus aureus (methicillin-susceptible isolates only) Streptococcus pneumoniae Streptococcus pyogenes Viridans group streptococci

The spectrum of activity of cefepime includes:

• Gram-negative bacteria: Enterobacter spp, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa
• Gram-positive bacteria: Staphylococcus aureus (methicillin-susceptible isolates only), Streptococcus pneumoniae, Streptococcus pyogenes, Viridans group streptococci The recommended dose of cefepime is:
• 1 to 2 g IV every 8 to 12 hours for moderate to severe pneumonia
• 2 g IV every 8 hours for empiric therapy for febrile neutropenic patients
• 0.5 to 1 g IV/IM every 12 hours for mild to moderate uncomplicated or complicated urinary tract infections
• 2 g IV every 12 hours for severe uncomplicated or complicated urinary tract infections
• 2 g IV every 12 hours for moderate to severe uncomplicated skin and skin structure infections
• 2 g IV every 8 to 12 hours for complicated intra-abdominal infections (used in combination with metronidazole) 2

From the Research

Cefepime Tazobactam Spectrum

• Cefepime/tazobactam has a broad spectrum of activity against Enterobacterales with AmpC enzymes and extended-spectrum β-lactamases (ESBLs), including those with ertapenem resistance, suggesting porin loss 3
• The combination is active against > 90% of Enterobacterales with OXA-48 and KPC carbapenemases, although the MICs for KPC producers belonging to the international Klebsiella pneumoniae ST258 lineage are higher 3
• Cefepime/tazobactam is less active than ceftolozane/tazobactam against Pseudomonas aeruginosa with AmpC de-repression or high-level efflux, but achieves wider antipseudomonal coverage than piperacillin/tazobactam 3
• The activity of cefepime/tazobactam against other non-fermenters is species-specific 3

Cefepime Tazobactam Dose

• The dose of cefepime/tazobactam is 2+2 g q8h with a 90-min infusion 3
• This dosing regimen is preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations 4

Comparison with Other Antibiotics

• Cefepime/tazobactam has a spectrum exceeding those of piperacillin/tazobactam and ceftolozane/tazobactam, and resembling or exceeding that of carbapenems 3
• The combination has genuine potential to be 'carbapenem-sparing' 3
• Cefepime/tazobactam is being developed as a potential carbapenem-sparing agent, with activity against ESBLs, and is currently in clinical development 4