From the Guidelines
Vancomycin and cefepime should not be used together as a standard initial empiric antibiotic regimen for fever and neutropenia, unless there are specific clinical indications, such as suspected catheter-related infection, skin or soft-tissue infection, pneumonia, or hemodynamic instability, as recommended by the Infectious Diseases Society of America 1.
Clinical Considerations
When considering the use of vancomycin and cefepime, it's essential to weigh the benefits and risks, particularly in patients with neutropenia. The combination may be necessary in certain situations, such as:
- Suspected catheter-related infection
- Skin or soft-tissue infection
- Pneumonia
- Hemodynamic instability In these cases, vancomycin can provide coverage against gram-positive organisms, including MRSA, while cefepime covers gram-negative organisms, including Pseudomonas.
Dosing and Administration
If the combination is deemed necessary, typical dosing for vancomycin is 15-20 mg/kg IV every 8-12 hours, with therapeutic drug monitoring to maintain trough levels of 15-20 mcg/mL for serious infections. Cefepime is typically dosed at 1-2 grams IV every 8-12 hours. Both medications require dose adjustment in renal impairment.
Mechanism of Action
Vancomycin targets cell wall synthesis in gram-positive bacteria by binding to D-Ala-D-Ala peptides, while cefepime, a fourth-generation cephalosporin, inhibits cell wall synthesis in gram-negative bacteria through binding to penicillin-binding proteins.
Therapy Adjustment
Once culture results are available, therapy should be narrowed to the most appropriate agent(s) to reduce the risk of resistance development and adverse effects, as recommended by the Infectious Diseases Society of America 1. This approach is supported by the 2010 update, which emphasizes the importance of tailoring antibiotic therapy to the individual patient's needs and reducing unnecessary antibiotic use 1.
From the Research
Combination of Vanc and Cefepime
- The combination of vancomycin and cefepime has been studied in several research papers, with a focus on its efficacy and safety in treating various infections 2, 3, 4.
- A prospective, multicenter observational study found that the incidence of acute kidney injury was significantly lower in patients treated with vancomycin and cefepime compared to those treated with vancomycin and piperacillin/tazobactam 2.
- Another study found that the combination of vancomycin and cefepime was associated with a lower incidence of acute kidney injury and a faster clearance of methicillin-resistant Staphylococcus aureus bloodstream infections compared to vancomycin alone 4.
- A propensity-matched cohort study found that the combination of vancomycin and cefepime was associated with a lower incidence of adverse events, including acute kidney injury, compared to the combination of vancomycin and piperacillin/tazobactam 3.
Efficacy and Safety of Cefepime
- Cefepime is a broad-spectrum cephalosporin with enhanced coverage against Gram-positive and Gram-negative bacteria 5, 6.
- A systematic review and meta-analysis found that cefepime was associated with a higher all-cause mortality compared to other beta-lactam antibiotics, although the difference was not significant in terms of treatment failure, superinfection, or adverse events 5.
- Cefepime has been found to be generally well tolerated, with a pharmacokinetic disposition similar to that of other renally eliminated cephalosporins 6.
- Cefepime has demonstrated clinical efficacy against a variety of infections, including urinary tract infections, pneumonia, and skin and skin structure infections 6.