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Decreased effectiveness of metronidazole in the treatment of infections caused by Clostridium difficile

Clostridium difficile is one of the agents responsible for serious nosocomial infections. Metronidazole is considered the drug of choice in the treatment of diseases caused by this pathogen because of its high efficacy (up to 90%) and its cost significantly lower than that of vancomycin. However, data obtained in recent years indicate a decrease in the effectiveness of metronidazole in the treatment of clostridial infections.

In a prospective observational study by D.M. Musher et al. (USA), the efficacy of metronidazole colitis caused by C.difficile has been evaluated. In the future, only 103 (50%) of the 207 patients were cured and relapsed. In 46 patients (22%), symptoms of colitis persisted after more than 10 days of treatment, and in 58 (28%) therapy was initially effective, but within 90 days of treatment, a relapse of infection has developed. Mortality during the study reached 27% and was higher with ineffective metronidazole treatment (33% vs 21%; p less than 0.05).

Another study undertaken by J. Pepin et al. (Canada), the objective was to study the efficacy of metronidazole in the treatment of diarrhea associated with C. difficile. According to the data obtained, the frequency of treatment failures was relatively stable for the period from 1991 to 2002. and amounted to 9.6% (66 out of 688 patients), but it increased almost twice over the period from 2003 to 2004, reaching 25.7% (112 out of 435 patients; p less than 0.001). The risk of relapse on day 60 with metronidazole monotherapy also increased significantly in 2003-2004. compared to 1991-2002. (47.2% vs 20.8%, respectively; p less than 0.001). It was noted that among patients aged 0 to 17, 18 to 64 and over 65, this indicator was 20.0%, 13.8% and 28.9% in 1991-2002. compared to 25.0%, 27.1% and 58.4% respectively in 2003-2004.

These data indicate a decrease in the efficacy of metronidazole in the treatment of infections caused by C.difficile, especially in elderly patients. To increase the effectiveness of treatment, it is necessary to seek new therapeutic approaches, in particular the development of new drugs and the use of already known drugs, such as antibiotics tinidazole and vancomycin, probiotics (Saccharomyces boulardii and lactobacilli), immunotherapy (using monoclonal antibodies) to neutralize the toxin C.difficile) and vaccination.