Norepinephrine modified the interaction between Escherichia coli and levofloxacin, potentially affecting clinical outcomes and increasing the risk of bacterial colonization

Abstract

Background: Norepinephrine is the most used vasopressor in intensive care units. It can modulate gene expressions and metabolism pathways in Escherichia coli. As fluoroquinolone’s bactericidal activity is affected by bacterial metabolism and growth rate, simultaneous exposure to these medications might alter the interaction between E. coli and levofloxacin. This study aims to investigate the effect of norepinephrine and levofloxacin given simultaneously on the in vitro growth of E. coli. Methods: Ten clinical isolates of E. coli were grown in minimal nutrition media with and without norepinephrine, levofloxacin, or both. Bacterial growth was observed for 20 h, and viable cell count was done every 2 h. Growth curves and generation times for each study group were calculated. Statistical analysis compared the viable cell counts on the 4, 14, and 20 h observation time points and the generation times. Results: Temporary inhibition of E. coli growth was observed until 4h of incubation when therapeutic concentrations of norepinephrine and levofloxacin were given simultaneously, followed by regrowth. The viable cell count of the norepinephrine–levofloxacin group was significantly lower than the control group by the 14 h and 20 h time points. Interestingly, the study group's average generation time of regrowth was 19.3 min, which was significantly faster than the control group (p < 0.05). Conclusion: Norepinephrine caused alterations in the interaction between E. coli and levofloxacin, which may affect clinical outcomes and increase the risk of bacterial colonization in patients receiving simultaneous norepinephrine and levofloxacin therapy.