الفهرس 
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Abstract
Background: Typhoid fever remains as a global and endemic public health problem, especially in developing countries. World Health Organization has estimated 21 million new cases of typhoid occur each year, resulting in approximately 216,000 deaths. For several decades, chloramphenicol was the recommended drug after its institution in 1948, Ampicillin and cotrimoxazole were used to cover chloramphenicol resistance but were discarded because of the emergence of plasmid-mediated multidrug resistance that enclosed all three drugs (WHO termed as multidrug resistant S. typhi). In the 1990s, ciprofloxacin was used as the drug of choice in treating MDR strains of S. typhi. The fluoroquinolones, including ciprofloxacin, were preferred to third-generation cephalosporins because they were accessible for oral use, less expensive, low rate of post treatment carriage and rapid clearance of fever and symptoms. However, in the preceding decade, S. typhi strains that show decreased ciprofloxacin susceptibility have emerged due to the improper usage of antibiotics, and patients having infection with these strains didn’t respond to therapy with fluoroquinolone Aim: This work was carried out to isolate S. typhi obtained from enterica cases, determination of their antimicrobial resistance pattern especially resistance to quinolones and molecular analysis of ciprofloxacin resistant S. typhi by testing gyrA mutation as a possible mechanism for quinolones resistance using PCR-RFLP and sequencing methods. Setting: Microbiology Diagnostics and Infection Control Unit (MDICU), in the Medical Microbiology and Immunology Department, Faculty of Medicine, Mansoura University. Results: This study was conducted over a period of eighteen months from March 2015 till October 2016, and included 250 patients with clinically suspected typhoid fever. Salmonella isolates represented 44% of all isolated pathogens. The E-test for ciprofloxacin proved that 70.2% of S. typhi was confirmed to be ciprofloxacin resistant. Multidrug resistance was detected in 85% of ciprofloxacin resistant S. typhi. Regarding antibiotic sensitivity of isolated S. typhi, it was found that the most effective antibiotics were ceftriaxone, followed by azithromycin, while the least effective was tetracycline. By PCR-RFLP, 90% of ciprofloxacin resistant S. typhi was found to have a mutation in the QRDR of the gyrA gene with a Ser83-Phe substitution (TCC→TTC), which was confirmed by sequencing results. Conclusion: Ciprofloxacin can no longer be considered as the drug of choice in treating typhoid fever. It is the need of the hour that the health care authorities should formulate alternative treatment guidelines including azithromycin and ceftriaxone. Continuous surveillance of the plasmid and chromosome of Salmonella species is essential to alter treatment strategies aimed at maintaining the useful life of the few remaining antimicrobials available to treat enteric fever.