Eravacycline in Critically Ill Patients with Multidrug-Resistant Gram-Negative Infections: A Real-World Cohort Study

Background: Multidrug-resistant Gram-negative infections remain a major challenge in critically ill patients, particularly when caused by carbapenem-resistant pathogens with limited therapeutic options. Although eravacycline has emerged as a potential salvage agent, real-world data in high-acuity intensive care populations remain scarce. Methods: We conducted a retrospective cohort study including adult ICU patients who received eravacycline as salvage therapy for multidrug-resistant Gram-negative infections between February 2024 and September 2025 in a tertiary-care center. Demographic, clinical, microbiological, and treatment-related variables were extracted from electronic records. Infection complexity was classified as monomicrobial single-site, monomicrobial multi-site, or polymicrobial. The primary outcome was in-hospital mortality; secondary outcomes included clinical response, microbiological eradication, and safety. Results: Forty critically ill patients were included (median age 58 years, IQR 47-69; mean APACHE II 16.4 ± 6.9; mean SOFA 5.5 ± 3.3). Pulmonary (62.5%) and intra-abdominal (55.0%) infections were most frequent. Klebsiella pneumoniae predominated (75.0%), followed by Acinetobacter baumannii (35.0%) and Pseudomonas aeruginosa (22.5%). Most patients received combination antimicrobial therapy. Microbiological eradication or presumed eradication was documented in 24 patients (60.0%), yet overall in-hospital mortality remained high (75.0%). Baseline disease severity and persistent inflammatory response were more strongly associated with unfavorable outcomes than treatment timing or duration. Conclusions: In this real-world ICU cohort, eravacycline-based salvage therapy was associated with moderate microbiological response but very high mortality, reflecting the severity of underlying critical illness. The dissociation between microbiological eradication and survival suggests that outcomes are more closely related to host factors and unresolved systemic inflammation than to pathogen clearance alone. Eravacycline remains one of the few agents active against MDR Gram-negative pathogens (with no activity against Pseudomonas aeruginosa), frequently used off-label; larger controlled studies are needed to establish efficacy beyond complicated intra-abdominal infections.