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CefepimeEdit

Cefepime is a broad-spectrum, intravenous fourth-generation cephalosporin antibiotic used primarily in hospital settings to treat serious or complicated infections. It belongs to the larger family of cephalosporins, a subset of β-lactam antibiotics that act by blocking bacterial cell-wall synthesis. Cefepime is designed to combine strong activity against a wide range of Gram-negative bacteria with reliable activity against many Gram-positive organisms, while offering relatively limited anaerobic coverage. In clinical practice, it is often employed for empiric therapy in severe infections and for coverage of nosocomial pathogens, with ongoing stewardship guiding de-escalation when culture data become available.

From a pharmacologic standpoint, cefepime exerts a time-dependent, bactericidal effect by binding to multiple penicillin-binding proteins (PBPs) and preventing cross-linking of the bacterial cell wall. Its pharmacodynamic profile supports frequent assessments of dosing in relation to renal function, since cefepime is primarily eliminated by the kidneys. The drug can cross the blood-brain barrier when meninges are inflamed, which has both therapeutic and safety implications in central nervous system infections and in managing markedly ill patients. Cefepime is typically administered by intravenous or intramuscular injection, and dosing must be adjusted in renal impairment to avoid accumulation and toxicity.

Historically, cefepime was approved in the 1990s and has since become a mainstay in inpatient antimicrobial therapy. It is marketed under the brand name Maxipime and is also available as generic cefepime in many regions. The drug features prominently in guidelines for severe pneumonia, intra-abdominal infections, febrile neutropenia, and other complicated infections, though its use is tempered by considerations of antimicrobial resistance and the desire to preserve broad-spectrum agents for when they are truly needed. The balance between immediate patient needs and long-term public health considerations—namely, antibiotic resistance and ecosystem pressure—is a central theme in how cefepime is prescribed in modern practice. In this context, discussions about cefepime frequently touch on broader debates about antibiotic stewardship and how to optimize outcomes while minimizing resistance.

Mechanism of action

Cefepime, like other cephalosporins, belongs to the class of β-lactam antibiotics and acts by inhibiting bacterial cell-wall synthesis. It achieves this by binding to several penicillin-binding proteins (PBPs), which disrupts the cross-linking of peptidoglycan and leads to bacterial cell death. This mechanism underpins its bactericidal activity and helps explain why it is effective against many Gram-negative rods and several Gram-positive cocci, particularly when used in the appropriate clinical context.

Spectrum of activity

Cefepime exhibits a broad spectrum that makes it useful for several serious infections, but it is not universally effective against all pathogens. Its activity profile includes:

  • Gram-positive bacteria: activity against many streptococci and methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci, with varying usefulness against resistant strains. It is generally less active against MRSA and enterococci. Streptococcus species are common targets.

  • Gram-negative bacteria: strong activity against many members of the Enterobacterales family, including Escherichia coli, Klebsiella spp., and Enterobacter spp., as well as other Gram-negative pathogens such as Pseudomonas aeruginosa and Haemophilus influenzae. This broad Gram-negative coverage is a hallmark of cefepime’s fourth-generation designation.

  • Anaerobes: cefepime has relatively limited activity against anaerobic bacteria and is not considered a reliable agent for infections where anaerobes are suspected or confirmed (for example, some intra-abdominal infections where anaerobic coverage is important). This characteristic differentiates cefepime from certain other beta-lactams with stronger anaerobic activity, and it influences decisions about combination therapy when anaerobes are a concern. Anaerobe infections are typically addressed with other agents or with combination regimens.

  • Resistance considerations: like all beta-lactams, cefepime is susceptible to inactivation by certain beta-lactamases. It is more stable in the presence of many common beta-lactamases than earlier cephalosporins, but resistance can still arise via mechanisms such as production of AmpC beta-lactamases or extended-spectrum beta-lactamases (ESBLs), porin loss, and efflux. Clinicians monitor local resistance patterns to guide empiric choices and to implement de-escalation when culture data are available. β-lactamases and antibiotic resistance dynamics are central to discussions about cefepime’s ongoing role in therapy.

Pharmacokinetics and pharmacodynamics

Cefepime is administered parenterally and is primarily eliminated by the kidneys. Its pharmacokinetic profile necessitates dose adjustment in patients with renal impairment to mitigate accumulation and toxicity risk. The drug’s activity is time-dependent, with efficacy correlating to the duration that drug concentrations exceed the pathogen’s minimum inhibitory concentration (MIC) during a dosing interval. Cefepime can penetrate the central nervous system when meninges are inflamed, contributing to its utility in treating CNS infections when indicated. Practitioners consider factors such as age, weight, kidney function, and the specific infection site when determining dosing regimens and infusion strategies.

Clinical uses and considerations

Cefepime is indicated for a range of serious infections, particularly those encountered in hospital settings. Common uses include:

Dosing decisions take into account infection severity, patient comorbidities, and local resistance patterns. In many settings, cefepime is part of an empiric regimens until culture data permit de-escalation to narrower agents. Clinicians also weigh the importance of stewardship—preserving cefepime’s effectiveness for future patients by avoiding unnecessary broad-spectrum use and by promptly narrowing therapy when appropriate. Antibiotic stewardship programs aim to optimize outcomes while reducing the development and spread of resistance.

Safety, adverse effects, and cautions

As with other beta-lactam antibiotics, cefepime can cause hypersensitivity reactions in susceptible individuals. Cross-reactivity with penicillins is a consideration for patients with a history of severe allergy. Common adverse effects include rash, diarrhea, and local injection-site reactions; antibiotic-associated diarrhea and, in some cases, Clostridioides difficile infection may occur. Cefepime carries a risk of neurotoxicity, including confusion, tremors, myoclonus, and seizures, particularly in patients with renal impairment or those receiving high doses. These events are more likely when drug exposure is high or when the patient’s renal function is reduced. Clinicians monitor for neurologic symptoms and adjust therapy accordingly. As with all antimicrobials, inappropriate use can contribute to the selection of resistant organisms, underscoring the ongoing relevance of stewardship principles. Clostridioides difficile infection is a known risk with broad-spectrum antibiotics, and appropriate infection-control and antimicrobial stewardship measures help mitigate this risk.

History and regulatory status

Cefepime was developed as a fourth-generation cephalosporin and received regulatory approval for clinical use in the 1990s. It has since become a standard option for treating severe infections in hospital settings, reflecting both the clinical demand for broad-spectrum Gram-negative coverage and the ongoing evolution of beta-lactam pharmacology. Brand and generic formulations are available, and cefepime is used in healthcare systems around the world under various national and local guidelines. Its place in therapy continues to be shaped by ongoing surveillance of resistance patterns, clinical outcomes, and stewardship practices.

See also