OBJECTIVES: To study the potential factors include gene mutation, efflux pump 
and alteration of permeability associated with quinolone-resistance of 
Salmonella enterica strains isolated from patients with acute gastroenteritis 
and to evaluate the degree of synergistic activity of efflux pump inhibitors 
when combined with ciprofloxacin against resistant isolates.
METHODS: Antimicrobial resistance patterns of fifty-eight Salmonella isolates 
were tested. Five isolates were selected to study the mechanism of resistance 
associated with quinolone group, including mutation in topoisomerase-encoding 
gene, altered cell permeability, and expression of an active efflux system. In 
addition, the combination between antibiotics and efflux pump inhibitors to 
overcome the microbial resistance was evaluated.
RESULTS: Five Salmonella isolates totally resistant to all quinolones were 
studied. All isolates showed alterations in outer membrane proteins including 
disappearance of some or all of these proteins (Omp-A, Omp-C, Omp-D and Omp-F). 
Minimum inhibitory concentration values of ciprofloxacin were determined in the 
presence/absence of the efflux pump inhibitors: carbonyl cyanide 
m-chlorophenylhydrazone, norepinephrin and trimethoprim. Minimum inhibitory 
concentration values for two of the isolates were 2-4 fold lower with the 
addition of efflux pump inhibitors. All five Salmonella isolates were amplified 
for gyrA and parC genes and only two isolates were sequenced. S. Enteritidis 22 
had double mutations at codon 83 and 87 in addition to three mutations at parC 
at codons 67, 76 and 80 whereas S. Typhimurium 57 had three mutations at codons 
83, 87 and 119, but no mutations at parC.
CONCLUSIONS: Efflux pump inhibitors may inhibit the major AcrAB-TolC in 
Salmonella efflux systems which are the major efflux pumps responsible for 
multidrug resistance in Gram-negative clinical isolates.