Effect of combination therapy between thyme oil and ciprofloxacin on ulcer-forming Shigella flexneri

Introduction: Shigella flexneri is a Gram-negative bacteria that has the ability to invade the epithelium of the colon and cause colon ulcers. Methodology: The ability of isolated Shigella flexneri from bloody diarrhea to cause colon ulcers was investigated by histopathological examination via oral administration of the bacteria to adult male albino Sprague-Dawley rats. The antibacterial activity of thyme oil, ciprofloxacin, and their combination were evaluated in vitro and in vivo. Results: Oral administration of 12 x 10(8) CFU/mL of S. flexneri was able to cause colon ulcers. Thyme oil had the highest antibacterial activity among other investigated oils (minimum inhibitory concentration [MIC] 150 mu L/L). Ciprofloxacin had the highest antimicrobial activity against S. flexneri (MIC 0.4 mg/L). The synergism between thyme oil and ciprofloxacin showed the maximum growth inhibition of S. flexneri. The synergistic activity of thyme oil and ciprofloxacin succeeded in healing the epithelial surface of the colon and decreased the inflammation of the lamina propria; it also decreased the bacterial load in the infected colon, while the commercial drug failed to heal the colon ulcer. Thyme oil, ciprofloxacin, and their combination showed different degrees of effects on the bacterial cell structure by transmission and scanning electron microscopes. Conclusions: The combination of thyme oil and ciprofloxacin gave synergistic activity, which proved to be more effective in inhibiting the growth of ulcer-forming S. flexneri, healing the colon ulcer, and decreasing infiltration of the lamina propria with inflammatory cells.