From the Research
For hypotensive septic shock, meropenem is generally preferred over cefepime due to its broader coverage against gram-negative organisms and lower risk of neurotoxicity. The recommended dose for meropenem is 1-2 grams intravenously every 8 hours, as supported by a study published in 2021 1. This study compared two empirical prolonged infusion dosing regimens for meropenem in patients with septic shock and found that both regimens led to a sufficiently high percentage of time the free drug concentration was above various target MICs for pathogens with target MICs < 4 mg/L.
Key Considerations
- Meropenem offers broader coverage against gram-negative organisms including Pseudomonas aeruginosa, extended-spectrum beta-lactamase (ESBL) producers, and anaerobes, making it more appropriate for critically ill patients with septic shock where source control is paramount.
- Meropenem has better central nervous system penetration and a lower risk of neurotoxicity compared to cefepime, which is particularly important in critically ill patients who may have altered renal function.
- When initiating meropenem, it should be combined with other antibiotics like vancomycin (15-20 mg/kg IV every 8-12 hours) for MRSA coverage until cultures return.
- Meropenem should be administered as an extended infusion over 3 hours rather than a bolus to maximize time above MIC, as supported by a study published in 2017 2.
- Dose adjustments are necessary for renal impairment, and therapy should be de-escalated based on culture results as soon as possible to minimize resistance development.
Additional Evidence
A study published in 2023 3 compared the effect of meropenem versus piperacillin-tazobactam in critically ill patients with sepsis and septic shock, and found that meropenem had a lower mortality rate on ventilator-free days, vasopressor-free days, and hospital-free days. Another study published in 2020 4 compared the empirical high-dose and low-dose of meropenem in critically ill patients with sepsis and septic shock, and found that high-dose meropenem may be more effective in treating septic shock. However, the most recent and highest quality study 1 supports the use of meropenem as the preferred treatment for hypotensive septic shock.