Antimicrobial resistance is a growing threat for humanity worldwide. A new definition of resistance, defined as difficult-to-treat resistance (DTR), has been made for Gram-negative infectious agents. DTR indicates resistance to all first-line treatment options, including all b-lactams (carbapenems and beta-lactamase inhibitor combinations) and fluoroquinolones. The aim of this study is to evaluate the antibiotic combinations used in clinical practice in the management of infections with difficult to treat microorganisms and the microbiological and clinical responses to this combination. In this study is a multicenter retrospective observational cohort study. Data were collected from 10 centers. The demographic factors, preferred combination and mortality status of patients that develops with a strain that the microorganism was found to be resistant in the antibiogram were determined. A total of 174 patients from seven different centers were included in the study. One hundred and forty-eight (85%) of the patients were hospitalized in the tertiary intensive care unit. The most common bacteria were Klebsiella spp. with a rate of 80 (45.9%). We observed an overall carbapenem resistance rate of 98.5% in Klebsiella spp., 100% both in Acinetobacter spp. and Pseudomonas spp. Conclusion: This study highlights the importance of combination treatments for DTR isolates.