Detection of mutations in the gyrA gene in fluoroquinolone resistance Salmonella enterica serotypes typhi and paratyphi A isolated from the Infectious Diseases Hospital, Kuwait

Background: Enteric fever due to Salmonella enterica is a major health problem, and fluoroquinolones such as ciprofloxacin are mostly the antibiotic of choice for treatment. Resistance to ciprofloxacin has been noticed to increase due to the emergence of new mutations in the bacterial DNA. Aims: To explore the fluoroquinolone resistance and molecular characterisation of reduced quinolone susceptibility in S typhi and S paratyphi A in Kuwait. Methods: 136 clinical isolates of S typhi and 40 of S paratyphi A were collected over five years. The antimicrobial susceptibility was studied by various methods. DNA sequencing of gyrA, gyrB, parC and parE genes was performed in 31 isolates. Results: There was a substantial difference in MIC range between the two serotypes, with the most common MIC for S typhi being 0.25 mg/l and for S paratyphi A being 1 mg/l. The proportion of nalidixic acid resistant strains increased gradually over the years. These strains had a significantly higher range of MIC of ciprofloxacin (0.023 mg/l to 1.0 mg/l) compared to the nalidixic acid sensitive strains (0.0016 mg/l to 0.125 mg/l). DNA sequencing of gyrA gene showed the presence of three different point mutations: Ser83 -> Phe in 17 strains, Ser83 -> Leu in 3 strains and Asp87 -> Asn in 6 strains. No mutations in the other genes were found. Conclusions: It is very important to keep searching for new mutations and continuously monitor drug resistance in different parts of the world in order to efficiently manage cases with enteric fever.