Antimicrobial Resistance in Salmonella Typhi Isolated From a Referral Hospital of Kathmandu, Nepal.

Purpose: The morbidity and mortality due to typhoid fever can be significantly reduced with the use of effective antibiotics. At present, fluoroquinolones, third generation cephalosporins, and azithromycin are widely used to treat typhoid fever. However, changing antibiotic susceptibility among Salmonella Typhi and Salmonella Paratyphi poses a particular challenge to the therapeutic management of enteric fever. The objective of this study was to assess the antibiotic susceptibility pattern of Salmonella Typhi isolates.

Patients and methods: A total of 706 blood specimens were collected from febrile patients attending the outpatient department of Kathmandu Model Hospital during June to September, 2018. The antibiotic susceptibility testing for 11 different antibiotics (nalidixic acid, ciprofloxacin, ofloxacin, levofloxacin, cefixime, ceftriaxone, cefotaxime, azithromycin, cotrimoxazole, chloramphenicol, and amoxicillin) was performed by disk diffusion method. Furthermore, minimum inhibitory concentration (MIC) values of ciprofloxacin, ofloxacin, and azithromycin were determined by agar dilution method. Mutation at gyrA ser83 associated with reduced susceptibility to fluoroquinolones was determined by PCR-RFLP.

Results: Out of 706 blood samples, 6.94% (n = 49) were culture positive for Salmonella enterica (S. Typhi, n = 46). It was revealed that 97.8% S. Typhi isolates were susceptible to conventional first-line antibiotics (ampicillin, chloramphenicol, and cotrimoxazole), 97.3% to cephalosporins and 95.7% to azithromycin. S. Typhi were either resistant or intermediately susceptible to fluoroquinolones: 97.8% to ciprofloxacin, 91.3% to ofloxacin, and 89.1% to levofloxacin. The MIC of ciprofloxacin, ofloxacin, and azithromycin for S. Typhi ranged from 0.008 to 32, 0.03 to 16, and 2 to 8 μg/mL, respectively. Out of 46 S. Typhi isolates, 44 (95.65%) had gyrA ser83 mutation.

Conclusion: Fluoroquinolones have poor activity against Salmonella Typhi. The trends of increasing azithromycin MIC value among S. Typhi might limit its use for the treatment of typhoid fever. Effectiveness of conventional first-line antibiotics in vitro suggests considering their clinical use after large-scale studies.