Factors associated with failure of metronidazole in Clostridium difficile-associated disease.
OBJECTIVE
To identify patients likely to fail metronidazole as initial treatment of C. difficile infection.


BACKGROUND
For moderate to severe Clostridium difficile-associated diarrhea, metronidazole is the drug of choice for treatment. Oral vancomycin is given to patients who fail metronidazole or have intolerable side effects.


METHODS
Retrospective review identified all patients treated for C. difficile-associated diarrhea during hospitalization from January 2000 to September 2001. C difficile was documented by a positive toxin assay or pseudomembranes on colonoscopy. Metronidazole failure was defined as persistent symptoms of C. difficile-associated diarrhea after 5 days of uninterrupted therapy. Response was defined as improvement in symptoms at day 5 of therapy including reduction of diarrhea to <or=2 bowel movements per day.


RESULTS
119 C. difficile-associated diarrhea patients were identified, and 99 met inclusion criteria. There were 61 (62%) metronidazole responders and 38 (38%) treatment failures. Albumin <2.5g/l and intensive care unit stay at/prior to diagnosis were the only variables associated with treatment failure. The odds ratios for treatment failure were 11.7 (95% confidence interval: 4.0-31.6) and 4.1 (95% confidence interval: 1.3-12.2), respectively. When considering these 2 variables together (low albumin, intensive care unit care), the area under the receiver operating characteristic curve was 0.80 for predicting treatment failure.


CONCLUSIONS
Albumin level <2.5g/l and intensive care unit stay were predictors of failure of metronidazole therapy for C. difficile-associated diarrhea. These patients may benefit from oral vancomycin therapy at outset.
Fernandez
Angel
A
Section of Gastroenterology, Temple University Hospital, Philadelphia, PA 19140, USA.
Anand
Girish
G
Friedenberg
Frank
F
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000418:Albumins / Q000032:analysis; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016360:Clostridioides difficile / Q000187:drug effects*; D003967:Diarrhea / Q000188:drug therapy* / Q000382:microbiology; D005260:Female; D006801:Humans; D007902:Length of Stay; D008297:Male; D008795:Metronidazole / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D012189:Retrospective Studies; D017211:Treatment Failure; D014640:Vancomycin / Q000627:therapeutic use
D000418:Albumins; D000890:Anti-Infective Agents; D008795:Metronidazole; D014640:Vancomycin