정장제, probiotics 효과: 감염성 설사, 항생제와 정장제의 동시 복용

Saccharomyces boulardii

Bacillus licheniformis

Bacillus subtilis/Enterococcus faecium

 

 

 

Infect Chemother 2010;42(6):323-361

 

 

Clinical Infectious Diseases 66.7 (2018): e1-e48.

여러 메타 분석에 따르면 항생제 치료를 받는 CDI 이력이 없는 환자에게 정장제를 투여했을 때 CDI를 예방하는데 효과적일 수 있다.

The studies with the greatest influence on the results of the meta-analyses had a CDI incidence 7–20 times higher in the placebo arms than would otherwise be expected based on the patient population studied, potentially biasing the results to benefit of the probiotic.

편향된 연구가 제외되어도 CDI 감소 추세는 여전하지만, 이들 연구가 포함되었을 때만큼 크지 않다. 정장제 자체가 환자에게 감염을 일으킬 가능성도 존재한다. 이러한 이유로 CDI 1차 예방을 위해 정장제 투여를 권고하기에는 자료가 부족하다.

 

 

 

Cochrane Database of Systematic Reviews 12 (2017).

Based on this systematic review and meta-analysis of 31 randomized controlled trials including 8672 patients, moderate certainty evidence suggests that probiotics are effective for preventing CDAD (NNTB = 42 patients, 95% CI 32 to 58). Our post hoc subgroup analyses to explore heterogeneity indicated that probiotics are effective among trials with a CDAD baseline risk >5% (NNTB = 12; moderate certainty evidence), but not among trials with a baseline risk ≤5% (low to moderate certainty evidence). Although adverse effects were reported among 32 included trials, there were more adverse events among patients in the control groups. The short-term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics.

 

👉Dose

The criteria supporting a dose dependent effect are mixed and we are unable to clearly identify a credible dose dependent effect at this time.

 

👉Species (alone and in combination)

In evaluating the subgroup species, there were two examples of a statistically significant test for subgroup effects. For the CDAD outcome, comparing the L. acidophilus + L. casei subgroup (RR 0.21, 95% CI 0.11 to 0.42, I2 = 0%, n = 781) to the L. rhamnosus subgroup (RR 0.63, 95% CI 0.30 to 1.33, I2 = 88%, n = 1031) resulted in a statistically significant test of subgroup difference (P = 0.03).

We are unaware of any biological or direct evidence that suggests that L. acidophilus + L. casei is superior to L. rhamnosus in terms of efficacy for CDAD nor that adverse events would be species specific.

The criteria supporting a species specific effect are mixed and we are unable to clearly identify a credible subgroup effect.

 

 

 

Canadian Journal of Gastroenterology 23.12 (2009): 817-821.

The present review of four trials suggests that there may be some benefit in using S boulardii for treatment and secondary prevention in patients experiencing recurrent CDI in conjunction with a particular concurrent antibiotic treatment. Because only a small number of studies address the primary prevention of CDI, more research is required before any changes in practice can be recommended with regard to using S boulardii prophylactically. The risks of administering S boulardii seem to be minimal compared with placebo, but because of case reports of potential morbidity secondary to serious fungemia, the use of this yeast agent should be considered on a case-by-case basis.

 

 

 

Antibiotics 6.4 (2017): 21.

항생제 사용의 일반적인 부작용은 설사이다. 정장제(probiotics)는 살아있는 미생물로, 불균형 gastrointestinal flora의 정상화에 의해 항생제 관련 설사(antibiotic-associated diarrhea; AAD)를 예방할 수 있다. 이 체계적인 검토의 목적은 외래환자 환경에서 AAD 예방에 사용되는 정장제의 장점과 위해성을 평가하는 것이었다.

PubMed 데이터베이스의 검색이 수행되었고 3631명의 참가자가 검토에 포함되도록 총 17개의 RCT를 산출했다. 주요 결과인 AAD 발생에 대한 메타 분석이 수행되었다.

대조군에서 정장제군에 비해 AAD의 더 많이 발생하였다.(17.7% vs 8.0%, RR 0.49, 95% CI 0.36~0.66; I2 = 58%) 정장제 종류에 따른 결과는 유사하였다.(균주 L. rhamnosus GG와 S boulardii). 그러나 포함된 연구의 전반적인 품질은 보통 수준이었다.(the overall quality of the included studies was moderate) 약물 부작용이 보고된 10개 시험의 메타 분석은 대조군과 정장제군은 통계적으로 유의미한 차이를 보이지 않았다(RD 0.00, 95% CI -0.02 - 0.02, 2.363 참여자).

결론적으로 정장제 사용이 외래환자의 AAD 예방에 도움이 될 수 있음을 시사한다. 게다가, 정장제의 사용은 안전한 것처럼 보인다.

 

 

 

 

reference:

1) 소화기계 감염 진료지침 권고안, Infect Chemother 2010;42(6):323-361

2) McDonald, L. Clifford, et al. "Clinical practice guidelines for Clostridium difficile infection in adults and children: 2017 update by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA)." Clinical Infectious Diseases 66.7 (2018): e1-e48.

3) Goldenberg, Joshua Z., et al. "Probiotics for the prevention of Clostridium difficile‐associated diarrhea in adults and children." Cochrane Database of Systematic Reviews 12 (2017).

4) Tung, Jennifer M., Lisa R. Dolovich, and Christine H. Lee. "Prevention of Clostridium difficile infection with Saccharomyces boulardii: a systematic review." Canadian Journal of Gastroenterology 23.12 (2009): 817-821.

5) Blaabjerg, Sara, Daniel Maribo Artzi, and Rune Aabenhus. "Probiotics for the prevention of antibiotic-associated diarrhea in outpatients—a systematic review and meta-analysis." Antibiotics 6.4 (2017): 21.