Background: Numerous recent studies suggest that bacteria play a role in the pathogenesis and/or symptoms of Crohn's disease. Metronidazole and ciprofloxacin have been shown to be efficacious for treating perianal disease. A recent study in adults demonstrated that metronidazole in combination with ciprofloxacin can be used as a possible alternative to steroid therapy to treat Crohn's flares.
Aim: To evaluate whether there is a role for metronidazole in combination with ciprofloxacin for treating mild to moderate pediatric Crohn's flares.
Methods: All Crohn's patients between 6-22 years old with signs and symptoms of active disease and a Pediatric Crohn's Disease Activity(PCDAI) between 20-42.5 were recruited for the study. Patients were excluded if in the past month they had 1) received antibiotics 2) received steroids at a dose greater than 10 mg QD for patients ≥35 kg or 5 mg QD for patients<35 kg or 3) an increase in their steroid dose. All patients were treated with both metronidazole and ciprofloxacin for 12 wks, without any other changes in their medical care. Patients were followed prospectively for 12 wks and PCDAI's determined at the initial visit, wk 4, wk 8, and at the end of the 12-wk study period.
Results: 9 patients were included in the study. Two patients were withdrawn from the study (one at 3 wks, one at 2 months) after showing clinical deterioration. All of the remaining 7 patients who completed the study showed clinical improvement which was defined as an improvement of½ standard deviation or greater between the baseline and post-treatment PCDAI scores. 6/7 (86%) had an improvement of greater than 1 standard deviation between baseline and post-treatment PCDAI scores. The mean PCDAI, sedimentation rate (ESR), albumin, and hematocrit were determined at baseline in all 9 patients, and compared after 12 wks of therapy (or when the 2 patients were withdrawn from the study). The paired t test was used to determine statistical significance (p<0.05) between baseline and post-treatment values. The mean PCDAI was 31.1 ± 5.9 at baseline and 13.6 ± 10.6 at the end of therapy (p=0.001). The improvements in mean ESR and hematocrit were also found to be statistically significant (p=0.04, p=0.02); whereas the improvement in mean albumin was NS. Because of the small sample size and potentially skewed layout of the data, nonparametric statistics were also performed; the results were consistent with the paired t test. Side effects of the antibiotics included Clostridium difficile infection in 1 patient following the 3-month course of antibiotics, a peripheral neuropathy in 1 patient which resolved once the metronidazole dose was lowered, and diarrhea in several patients that subsequently resolved with a decrease in the ciprofloxacin dose.
Conclusions: 1) Metronidazole and ciprofloxacin are useful for treating mild to moderate pediatric Crohn's flares. 2) 7/9 (78%) of pediatric patients had clinical improvement. 3) There was a statistically significant improvement in mean PCDAI, ESR, and hematocrit when comparing baseline with post-treatment values.