2025 Southeastern Residency Conference

Title: Comparative Efficacy of Ertapenem in Patients with or without Hypoalbuminemia
Authors: Jakob Barton PharmD, Julia Coluccio PharmD, BCCCP, Kristin Fernandes PharmD, BCPS, Steven Parker PharmD
Background: Ertapenem, a carbapenem antimicrobial, is indicated for a wide range of bacterial infections including blood stream infections, complicated urinary tract infections, community acquired pneumonia, and complicated intra-abdominal infections. It has a broad spectrum of activity against multiple gram-positive organisms and gram-negative organisms including those that produce extended spectrum beta-lactamases (ESBL). According to the 2024 Update to the IDSA Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections, ertapenem is not the preferred carbapenem in critically ill patients or patients with hypoalbuminemia (defined as a serum albumin level of ≤2.5 g/dL). Pharmacokinetic studies have demonstrated a difference in drug concentrations among patients with normal albumin compared to those with hypoalbuminemia as ertapenem is highly protein bound. Hypoalbuminemia can lead to fewer available protein binding sites and increased free concentration of ertapenem, which may reduce the half-life of the drug and prevent it from achieving optimal minimum inhibitory concentration (MIC) targets. The purpose of this study is to evaluate if a difference is present in the rate of clinical cure with ertapenem therapy in patients with or without hypoalbuminemia.
Methodology: This was a retrospective chart review of patients admitted to Piedmont Atlanta Hospital from August 2022 to August 2024 who received ertapenem for at least 2 days and had a documented albumin level within 48 hours prior to ertapenem administration. Hypoalbuminemia was defined in this study as a serum albumin level prior to ertapenem administration of ≤2.9 g/dL. Patients were excluded if they were pregnant or if ertapenem was being used in combination with cefazolin for methicillin-susceptible Staphylococcus aureus bacteremia. The primary endpoint was the clinical cure rate within 10 days of ertapenem therapy defined as resolution of fever and leukocytosis. Secondary endpoints included 90-day readmission rates for infectious reasons, total duration of antimicrobial therapy, survival by hospital discharge and hospital length of stay. Statistical analysis was completed using an independent t-test for continuous data and Chi squared test for categorical data. In order to achieve an expected 85% cure rate it was determined that 92 patients were needed to reach 80% power with an alpha of 0.05. A p-value of <0.05 was statistically significant.
Results: A total of 154 patients were included in the study with 60 patients in the hypoalbuminemia group and 94 in the non-hypoalbuminemia group. In patients with hypoalbuminemia, 60% achieved clinical cure by day 10 compared to 70.2% of patients without hypoalbuminemia (p=0.1919). There was no difference in rates of readmission between the groups with 10% of patients in the hypoalbuminemia group being readmitted for an infectious reason compared to 21.3% in the patients without hypoalbuminemia (p=0.0685). No difference was found in rates of survival at discharge in the hypoalbuminemia group compared to the non-hypoalbuminemia group (82% vs 86%, p=0.4524) Ertapenem duration of therapy in the study was longer in the hypoalbuminemia group compared to the non-hypoalbuminemia group (8.9 days vs 6.6 days, p = 0.0109). Additionally, hospital length of stay was prolonged in the hypoalbuminemia group compared to the non-hypoalbuminemia group (35 days vs 16 days, p = 0.0002)
Conclusions: This study found no statistically significant difference in clinical cure rates at 10 days in patients with hypoalbuminemia compared to patients without hypoalbuminemia. Patients without hypoalbuminemia had significantly shorter lengths of stay in the hospital and shorter durations of therapy with ertapenem. Study limitations include retrospective design and a different of hypoalbuminemia than what is outlined in the guidance statement from IDSA. Prospective trials with a larger sample size are warranted in this population.