The combined antimicrobial activity of citrus honey and fosfomycin on multidrug resistant <em>Pseudomonas aeruginosa</em> isolates

Infections with Pseudomonas aeruginosa ( P. aeruginosa ) have become a real fear in hospital-acquired infections, especially in critically ill and immunocompromised patients. Thus, advance of novel anti-infectives is currently pursued. The aim of the present study was to evaluate the antibacterial effect of each of citrus honey and fosfomycin in comparison to the combined effect of both of them on multidrug resistant (MDR) P. aeruginosa . 50 MDR P. aeruginosa isolates were tested for the antibacterial effect of citrus honey. Screening for potential synergistic activity of fosfomycin and honey combinations by E test. Molecular detection of the virulent exoenzyme U ( exoU ) genotype by conventional PCR was done. The present study found that 50 % (v/v) concentration of citrus honey was sufficient to inhibit the growth of most isolates (33/50, 66%). Minimal inhibitory concentration (MIC) for fosfomycin tested by E test was found to be >128 µg/mL in 50(100%) of MDR P. aeruginosa isolates but after repeating E test with Mueller-Hinton agar (MHA) containing sublethal concentration of citrus honey (29/50,58%) isolates were sensitive. Also, there was a significant correlation between the presence of exoU gene and positive synergy of citrus honey-fosfomycin combination. This study showed that citrus honey has antibacterial effect and synergy with fosfomycin antibiotic against MDR P. aeruginosa isolates. Also, exoU positive genotype is associated with MDR phenotype. In conclusion, our results revealed that the citrus honey-fosfomycin combination showed highly statistically significant effect on MDR P . aeruginosa fosfomycin susceptibility pattern. exoU positive P. aeruginosa isolates were detected mostly in burn unit and ICUs. Also, there was a statistically significant correlation between the presence of exoU gene and positive result of honey-fosfomycin combination E test.