Should a loading dose of cefepime be administered before continuous infusion in a 40-year-old female patient with Pseudomonas aeruginosa bacteremia in the intensive care unit (ICU), considering its impact on clinical cure and mortality?

From the Guidelines

I strongly recommend giving a loading dose of cefepime before initiating continuous infusion for this patient with Pseudomonas aeruginosa bacteremia because of the increased likelihood of clinical cure and decreased likelihood of death. According to the guidelines from the French Society of Pharmacology and Therapeutics and the French Society of Anaesthesia and Intensive Care Medicine 1, administering a loading dose before continuous infusion of beta-lactams like cefepime is crucial to rapidly achieve therapeutic concentrations in the bloodstream. The Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016 also supports the use of loading doses for beta-lactams administered as continuous or extended infusions to accelerate accumulation of drug to therapeutic levels 1. Key points to consider include:

• The importance of rapidly achieving therapeutic drug levels in critically ill patients with altered pharmacokinetics
• The potential for delayed effective antimicrobial activity without a loading dose
• The improved clinical cure rates and reduced mortality associated with loading doses
• The recommendation for a loading dose of 25-30 mg/kg (based on actual body weight) for vancomycin, which can be extrapolated to other antibiotics like cefepime
• The need for therapeutic drug monitoring to ensure optimal drug levels and minimize toxicity. Overall, the use of a loading dose of cefepime before continuous infusion is supported by the available evidence and guidelines, and is likely to improve clinical outcomes in this patient with Pseudomonas aeruginosa bacteremia.

From the Research

Recommendation for Cefepime Loading Dose

The ICU team is considering the use of a loading dose of cefepime before continuous infusion for the treatment of Pseudomonas aeruginosa bacteremia in a 40-year-old female patient. Based on the available literature, the following points should be considered:

• The use of extended-infusion cefepime has been shown to reduce mortality in patients with Pseudomonas aeruginosa infections 2.
• A study found that a cefepime MIC of ≥4 mg/L was associated with a lower survival rate, and the use of a maximal cefepime dose did not improve outcomes in patients with a MIC of ≥4 mg/L 3.
• Extended-infusion antimicrobial regimens, including cefepime, have been used to treat multidrug-resistant Pseudomonas aeruginosa infections 4.
• Pharmacokinetic and pharmacodynamic studies have shown that continuous infusion of cefepime can provide serum drug concentrations continuously above the MIC for most bacterial pathogens 5, 6.
• However, there is no direct evidence to support the use of a loading dose of cefepime before continuous infusion to increase the likelihood of clinical cure and decrease the likelihood of death.

Key Considerations

• The available literature does not provide a clear recommendation for the use of a loading dose of cefepime before continuous infusion.
• The decision to use a loading dose should be based on individual patient factors and the specific clinical scenario.
• The use of extended-infusion cefepime and continuous infusion regimens may provide clinical and economic benefits in the treatment of Pseudomonas aeruginosa infections 2, 5, 6.