INTERNATIONAL GUIDELINES FOR THE TREATMENT OF CARBAPENEM-RESISTANT GRAM-NEGATIVE BACILLI: A CRITICAL EVALUATION BASED ON MULTICENTER DATA FROM BRAZIL

Infections caused by carbapenem-resistant gram-negative bacilli (CR-GNB) are associated with high morbidity and mortality. Treatment guidelines from national and international infectious disease societies recommend the use of new antimicrobials as first-line therapy; however, few studies compare the use of these new drugs within the Brazilian reality. The objective of this study was to analyze risk factors associated with 30-day mortality in patients with CR-GNB infections. This was a multicenter retrospective cohort study including patients over 17 years of age admitted to ten centers in four states—São Paulo, Bahia, Maranhão, and Espírito Santo—from January 2022 to December 2023, who received at least 48 hours of effective antibiotic therapy for CR-GNB infections. Patients with polymicrobial infections were excluded. The outcome analyzed was death within 30 days after infection. Bivariate and multivariate analyses were performed using Cox regression, and proportional hazards were assessed using Schoenfeld residual plots. Variables with p < 0.1 in bivariate analysis were included in the multivariate model; those that reduced −2 log-likelihood or had p ≤ 0.05 were retained in the final model. A total of 294 patients were included, with a median age of 61 years (20–89). Most isolates were Enterobacterales (62.2%), followed by P. aeruginosa (20.7%) and A. baumannii (17.0%). In 162 patients (55.1%), the pathogen was isolated from blood; the most common infection site was the lung (33% – 98), followed by primary bloodstream infection (32% – 94). The median SOFA score was 5 (0–17), and 30-day mortality was 55.1% (162). Variables associated with 30-day mortality in the final model were male sex (HR 1.91, p = 0.002), age in years (HR 1.02, p = 0.005), Charlson score (HR 1.12, p = 0.002), urinary focus (HR 0.30, p = 0.01), Enterobacterales infection (HR 1.78, p = 0.01), SOFA score (HR 1.15, p < 0.001), time to effective antibiotic therapy (HR 0.94, p = 0.02), closed focus of infection (HR 0.35, p = 0.02), CR-GNB isolated from tracheal secretion (HR 1.66, p = 0.02), and ascitic fluid (HR 3.21, p = 0.03). Treatment according to international guidelines was marginally protective (HR 0.70, p = 0.09). In conclusion, CR-GNB infections are associated with high mortality, and patient- and disease-related factors, as well as time to effective therapy, were more important than antimicrobial choice.