Nitrofurantoin Combined With Amikacin: A Promising Alternative Strategy for Combating MDR Uropathogenic Escherichia...

Area of Science:

• Microbiology and Infectious Diseases
• Pharmacology and Therapeutics
• Antimicrobial Resistance

Background:

• Urinary tract infections (UTIs) are prevalent and can range from mild to severe.
• Increasing bacterial resistance and poor patient adherence challenge conventional antibiotic treatments for UTIs.
• Multidrug-resistant (MDR) uropathogenic Escherichia coli (UPEC) poses a significant threat due to limited therapeutic options.

Purpose of the Study:

• To investigate the synergistic relationship between nitrofurantoin and amikacin against clinical MDR UPEC strains.
• To evaluate the efficacy of this combination therapy both in vitro and in an experimental Galleria mellonella infection model.

Main Methods:

• Utilized standard checkerboard and time-kill assays for in vitro synergy testing.
• Employed an experimental Galleria mellonella model to assess in vivo therapeutic efficacy.
• Tested 12 clinical MDR UPEC strains to ensure broad applicability.

Main Results:

• Demonstrated significant in vitro synergistic effects between nitrofurantoin and amikacin across all 12 MDR UPEC strains.
• Found that single-agent therapies (amikacin or nitrofurantoin at half clinical doses) were ineffective in the Galleria mellonella model.
• Observed a significant increase in Galleria mellonella survival when treated with the combination therapy against all tested UPEC strains.

Conclusions:

• Nitrofurantoin and amikacin exhibit synergistic activity against multidrug-resistant UPEC.
• The combination therapy shows promise for treating MDR UPEC infections, particularly where conventional treatments are failing.
• Further clinical investigation is warranted to explore the therapeutic potential of this synergistic antibiotic combination for UTIs.