Synergistic Antibacterial Activity of Combined Antimicrobials and the Clinical Outcome of Patients With Carbapenemase-Producing Infection.

This study aimed to explore the activity of combined antimicrobials , and the relationship among resistance mechanisms, antimicrobial regimens, and the clinical outcome of patients with carbapenem-resistant (CRAB) infections in western China. A total of 89 CRAB strains were collected from patients with CRAB infection from January 2018 to June 2018. The checkerboard assay was used to study the combined effects . Carbapenemase-encoding genes were detected by polymerase chain reaction (PCR) or multiplex PCR technique. The clinical data of 86 patients were collected. CRAB showed high susceptibility to tigecycline (91.01% inhibition) and polymyxin (83.15% inhibition). Polymyxin plus sulbactam exhibited the highest synergistic effect at a rate of 82.35%. Production of carbapenemase ( ) was the main resistance mechanism of CRAB to carbapenem (95.35%). Excessive expression of active efflux pump genes (, , and ) and deletion of the CarO protein accounted for 13.95% (12/86) and 84.88% (73/86), respectively. The synergistic effect of the sulbactam-based combination was higher than that of the polymyxin B-tigecycline combination for carbapenemase-producing CRAB ( < 0.05). The clinical outcome was not affected by the resistance mechanisms ( > 0.05). Advanced age, multiple organ dysfunction syndromes (MODS), and admission to the intensive care unit (ICU) were associated with treatment failure ( < 0.05). Appropriate antibiotic therapy did not improve the clinical outcome of critically ill patients. Higher minimum inhibitory concentrations (MICs) of tigecycline were associated with treatment failure ( < 0.05). A multivariate analysis showed that ICU stay (OR = 15.123, 95% CI: 2.600-87.951, = 0.002) and procalcitonin ≥2 ng/ml (OR = 2.636, 95% CI: 1.173-5.924, = 0.019) were the risk factors for treatment failure. In conclusion, this study demonstrated that the sulbactam-based combination exhibited a synergistic effect . The clinical outcome of patients was not associated with resistance mechanisms. This indicates that the early control of the progression from infection to severe disease may be important.