The activities of therapeutic regimens with ciprofloxacin, ofloxacin and levofloxacin (14 days, 40 mg/kg once a day) alone or in combination with doxycycline (14 days, 40 mg/kg twice a day) against chronic infection with Brucella melitensis were assessed in 200 mice. Doxycycline alone or in combination with ciprofloxacin significantly reduced the infection till 135 days post-infection (p<0.01 and p<0.05, respectively). In addition, doxycycline was more effective than ofloxacin 135 days post-infection (p<0.05). However, quinolone-doxycycline treatment revealed significant additive effect because they reduced the splenic CFU from the day 45 post-infection, whereas, the treatment with doxycycline alone reduced the splenic CFU from the day 90 post-infection.
Keywords: Antibiotic combinations, Brucella melitensis, chronic disease.
Brucellosis remains the most common and serious problem in some parts of the world.1 Many of Brucella species could infect animals through direct contact. Human could be infected when exposed to B. abortus, B. melitensis, or B. suis. In humans, the exhausting disease could become, over time, a chronic disease that affects several organs. Ingestion of unpasteurized dairy products, as well as occupational exposure to infected animals, are the major causes of brucellosis. In addition, Ariza et al. indicated that some species of Brucella could be used in a bioterrorist attack.2
In ruminants, no symptoms were seen after the first abortion; but these infected animals could develop a chronic disease and become chronic carriers, and during subsequent pregnancies, Brucella could be found in milk and uterine discharges of these carriers.3
Undulant fever, in human, recovers completely within three to twelve months, and only few patients suffering from chronic disease. However, relapses could be seen months after the initial symptoms. The most common complications, which seen occasionally in the undulant and chronic forms, are arthritis, spondylitis, meningitis and chronic fatigue.4-6
In mice, the most infected organs are spleen and liver. In splenectomized mice, the liver rapidly colonized with Brucella. So, during the chronic phases, the higher Brucella colonization of the spleen protects the liver from infection.7 Therefor, spleen is the best target organ to study Brucella infections. Chronic steady phase, or CFU plateau phase, commonly started at the 21 days and lasting till 56-77 days post-infection. At this phase, the maximum numbers of CFU within spleen are noticed. Whereas, the chronic declining phase, at which there is a slow elimination of the bacteria from target organs, may last beyond 252 days.8 Then, normally, experiments in mice are not prolonged more than 90-120 days. Large and prominent splenomegaly was rarely seen in ruminants.9 However, The sequelae observed in chronic brucellosis in humans have not been reported in mice.4
Finally, in practice, human chronic brucellosis is treated with antibiotic...