Ertapenem in the Context of Hypoalbuminemia: Implications for Critically Ill Patients

The global rise in extended-spectrum β-lactamase-producing Enterobacterales (ESBL-E) has created significant challenges in the management of severe infections, including bacteremia. Ertapenem, a once-daily carbapenem with high protein-binding affinity (85%-95%), is an ideal option for ESBL-E because of its spectrum and dosing convenience. However, hypoalbuminemia, a common condition in critically ill patients that is independently associated with poor outcomes, raises concerns about altered pharmacokinetics, specifically increased free drug fractions, enhanced clearance, and shortened half-life. These pharmacokinetic changes have been hypothesized to lead to suboptimal drug levels and treatment failure, although clinical evidence remains inconsistent. This narrative review examines ertapenem's pharmacokinetic and pharmacodynamic changes in patients with hypoalbuminemia, focusing on its clinical implications. While some studies have reported suboptimal outcomes in critically ill patients, others have demonstrated comparable efficacy to broader spectrum carbapenems when minimum inhibitory concentration values are favorable, and source control is achieved. These findings challenge the concerns raised in the 2024 Infectious Diseases Society of America Gram-negative resistance guidance, which cautions against ertapenem use in patients with hypoalbuminemia. Rather than universally avoiding ertapenem, clinicians should prioritize individualized decision making based on patient-specific factors. Further research is warranted to optimize dosing strategies. However, current data suggest that ertapenem remains a viable and effective option in this high-risk population when used judiciously.