Antibacterial Activity and Mechanism of Fusidic Acid Combined with Aztreonam Against Carbapenem-Resistant Pseudomonas aeruginosain In Vitro / 中国药学杂志

ABSTRACT

OBJECTIVE: To explore the antibacterial activity and mechanism of fusidic acid combined with aztreonam on 12 clinical isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA). METHODS: Broth dilution method was used to determine the minimum inhibitory concentration(MIC) of the fusidic acid and aztreonam combination.The MIC of two drugs combination were measured by the checkerboard method and partial inhibitory concentration index (FIC) was calculated to determine the combined effect.The synergistic effect of two drugs was assessed by the disk diffusion susceptibility test and the time-killing curves.Extracellular enzyme activity assay was used to detect the strains extracellular enzyme activity changes of fusidic acid alone and combined with aztreonam. The probable mechanism of the combined use of two drugs was discussed. RESULTS: Fusidic acid and aztreonam combination displayed synergistic and additive activity on 61.54% and 38.46% isolates, no antagonism activity was observed.The bacteriostasis circle was obviously increased in two drugs combination, of which 41.67% of the strains were changed from drug resistance to sensitive. The time-killing curves showed that the combined of two drugs had bactericidal effect on the isolate PA 320.Extracellular aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) activity were all increased in a significant difference with the combination of two drugs. CONCLUSION: Fusidic acid combined with aztreonam on CRPA is showed synergistic and additive activity in vitro. The mechanism of two drugs in combination may concern with aztreonam help the fusidic acid to overcome the natural hydrophobic antibiotic permeability barriers of gram-negative bacteria.