Cefepime,Tazobactam
Overview
Cefepime tazobactam is an investigational intravenous antibacterial combination consisting of cefepime, a fourth-generation cephalosporin, and tazobactam, a beta-lactamase inhibitor. Cefepime exerts bactericidal activity by binding to penicillin-binding proteins and inhibiting bacterial cell wall synthesis, leading to cell lysis. Tazobactam has minimal intrinsic antibacterial activity but inhibits certain beta-lactamase enzymes produced by resistant Gram-negative organisms, thereby protecting cefepime from enzymatic degradation. The combination is designed to expand activity against extended-spectrum beta-lactamase producing Enterobacterales and other multidrug-resistant Gram-negative pathogens. It is administered intravenously and has been evaluated primarily in hospitalized patients with serious infections. The rationale for this pairing is to enhance cefepime’s stability against beta-lactamase-mediated resistance while preserving its broad-spectrum coverage against Gram-positive and Gram-negative organisms.
Background and Date of Approval
Cefepime was originally approved by the United States Food and Drug Administration in 1996 for the treatment of moderate to severe bacterial infections. Tazobactam was approved in combination with piperacillin by the United States Food and Drug Administration in 1993. The fixed-dose cefepime tazobactam combination has been developed as an investigational product to address increasing antimicrobial resistance, including extended-spectrum beta-lactamase producing pathogens. Clinical development programs have included pharmacokinetic studies and Phase II and Phase III trials evaluating complicated urinary tract infections and other serious Gram-negative infections. As of current publicly available regulatory data, the fixed-dose cefepime tazobactam combination has not received formal marketing approval from the United States Food and Drug Administration or the European Medicines Agency.
Uses
Cefepime tazobactam has been studied for the treatment of complicated urinary tract infections, hospital-acquired infections, and other serious infections caused by resistant Gram-negative organisms. Its intended role is in settings where beta-lactamase production compromises the activity of standard cephalosporins. Clinical trials have primarily evaluated its use as monotherapy in hospitalized adults with confirmed or suspected multidrug-resistant infections.
Administration
In clinical studies, cefepime tazobactam has been administered intravenously, typically as intermittent infusions given multiple times daily. Dosage regimens in trials have been designed to optimize pharmacodynamic exposure of cefepime while maintaining effective beta-lactamase inhibition. Dose adjustments are generally required in patients with renal impairment due to cefepime’s predominant renal elimination. Duration of therapy depends on infection severity, microbiological response, and clinical stability.
Side Effects
Observed adverse effects in clinical studies have been similar to those seen with other beta-lactam antibiotics. Common reactions include gastrointestinal symptoms such as nausea and diarrhea, infusion site reactions, headache, and mild elevations in liver enzymes. Most adverse events have been mild to moderate in intensity and manageable with supportive care.
Warnings
Serious risks associated with cefepime-containing regimens may include hypersensitivity reactions, including anaphylaxis in patients with beta-lactam allergy, neurotoxicity particularly in patients with renal dysfunction, and Clostridioides difficile-associated diarrhea. Close monitoring is advised in patients with impaired renal function to reduce the risk of encephalopathy or seizures. Therapy should be discontinued if severe allergic reactions or significant neurologic toxicity occurs.
Precautions
Baseline assessment of renal function is recommended prior to initiation and during treatment. Caution is required in patients with known hypersensitivity to cephalosporins, penicillins, or other beta-lactam antibiotics due to potential cross-reactivity. Because cefepime is primarily renally excreted, concomitant use of nephrotoxic agents may increase toxicity risk. Classical cytochrome P450-mediated drug interactions are not expected to be clinically significant for this combination.
Expert Tips
Cefepime tazobactam should be considered in the context of antimicrobial stewardship and local resistance patterns. Microbiological confirmation and susceptibility testing are recommended whenever feasible. Renal dose adjustment is essential to reduce neurotoxicity risk. Monitoring should include clinical response, renal function, and evaluation for hypersensitivity reactions. Coordination with infectious disease specialists may be appropriate in cases of multidrug-resistant infections.