Eradication of pathogenic bacteria and restoration of normal pouch flora: comparison of metronidazole and ciprofloxacin in the treatment of pouchitis.
OBJECTIVE
Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Metronidazole and ciprofloxacin are commonly used for treatment; however, nothing is known about the effects on the pouch flora during and after pouchitis episodes. This study was designed to evaluate the effect of both antibiotics on eradication of pathogens and the restoration of normal pouch flora.


METHODS
The fecal flora obtained from 13 patients with ulcerative colitis was examined at the beginning of a pouchitis episode before treatment, during treatment with metronidazole or ciprofloxacin, and during pouchitis-free periods. Some patients experienced more than one pouchitis episode. Therefore, a total of 104 samples was obtained. Each sample was cultured under aerobic and anaerobic conditions and the isolated bacteria were identified. Furthermore, the clinical response to both antibiotics was compared using the Pouchitis Disease Activity Index score.


RESULTS
During pouchitis-free periods, the patients had a flora characterized by high numbers of anaerobes and no or low numbers of pathogens. This flora resembles normal colon flora. During pouchitis episodes, we found a significant decrease of anaerobes ( P = 0.01), a significant increase of aerobic bacteria ( P = 0.01), and significantly more numbers of pathogens, such as Clostridium perfringens (in 95 percent of the samples; P < 0.01) and hemolytic strains of Escherichia coli (in 57 percent of the samples; P = 0.05). Treatment with metronidazole resulted in a complete eradication of the anaerobic flora, including C. perfringens. However, no changes in the numbers of E. coli were found. In contrast, when the patient was treated with ciprofloxacin, not only C. perfringens, but also all coliforms including hemolytic strains of E. coli disappeared. The larger part of the anaerobic flora was left undisturbed during the administration of ciprofloxacin. Patients treated with ciprofloxacin experienced significant larger reductions in Pouchitis Disease Activity Index score compared with patients treated with metronidazole ( P = 0.04).


CONCLUSIONS
This study strongly suggests a role of pathogenic bacteria ( C. perfringens and/or hemolytic strains of E. coli) in pouchitis. From a microbiologic and a clinical point of view, ciprofloxacin is preferable to metronidazole, because treatment with ciprofloxacin eradicates both pathogens and results in an optimal restoration of normal pouch flora.
Gosselink
Martijn P
MP
Colorectal Research Group of the Department of Surgery, Erasmus MC, Rotterdam, The Netherlands.
Schouten
W Rudolph
WR
van Lieshout
Leo M C
LM
Hop
Willem C J
WC
Laman
Jon D
JD
Ruseler-van Embden
Johanneke G H
JG
D000328:Adult; D000890:Anti-Infective Agents; D002939:Ciprofloxacin; D003015:Clostridium Infections / Q000188:drug therapy; D003016:Clostridium perfringens / Q000254:growth & development / Q000472:pathogenicity; D003093:Colitis, Ulcerative / Q000601:surgery*; D004768:Enterotoxins / Q000032:analysis; D004926:Escherichia coli / Q000254:growth & development / Q000472:pathogenicity; D004927:Escherichia coli Infections / Q000188:drug therapy; D005243:Feces / Q000737:chemistry / Q000382:microbiology; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008297:Male; D008795:Metronidazole; D008875:Middle Aged; D019449:Pouchitis / Q000188:drug therapy*; D016737:Proctocolectomy, Restorative / Q000009:adverse effects*
D000890:Anti-Infective Agents; D004768:Enterotoxins; D008795:Metronidazole; D002939:Ciprofloxacin