實證醫學案例報告 台大急診 PGY 陳韋廷 Scenario 73 歲男性病患中風過後臥床, 此次因肺炎入院施打抗生素, 治療第五天後開始有嚴重腹瀉, 檢查後發現為 Clostridium difficile 造成之偽膜性大腸炎, 後開始使用 metronidazole 治療, 此時病人家屬詢問是否可以服用表飛鳴? 1
PICO 病患或族群 (Patient or Population) 介入或臨床指標 (Intervention or Indicator) 比較標的 (Comparator) 結果 (Outcome) The elderly infected with Clostridium difficile receving metronidazole Probiotics Placebo Efficacy Safety Are the elderly patients infected with Clostridium difficile receiving metronidazole benefited from the use of probiotics? Question 2
Secondary Database UpToDate MD Consult Keywords: probiotics AND Clostridium difficile Clostridium difficile and probiotics UpToDate 3
Clostridium difficile and probiotics In treatment: Less treatment failure and recurrence rates with standard antibiotics and S. boulardii in recurrent cases Not as the main treatment (Grade 2C) May be an adjunct to antimicrobial therapy therapy in recurrent CDAD Not in the severe cases Clostridium difficile and probiotics In prevention May be considered in elderly patients without significant cormorbidities receiving antibiotic therapy Administered as described in published studies demonstrating efficacy 4
Clostridium difficile and probiotics In safety Undereported bacteremia or fungemias Saccharomyces boulardii and Lactobacillus rhamnonsus GG (LGG) On immunosuppressive medication, recent surgical intervention, recent prolonged hospitalization 5
Clostridium difficile and probiotics Probiotics as prevention and treatment for diarrhea. Curr Opin Gastroenterol. 2009 Jan;25(1):18-23 Role of probiotics in antibioticassociated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficileassociated diarrhea. J Clin Gastroenterol. 2008 Jul;42 Suppl 2:S64-70 Systematic review Systematic review Clostridium difficile and probiotics McFarland, LV. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am J Gastroenterol 2006; 101:812 Pillai, A, Nelson, R. Probiotics for treatment of Clostridium difficileassociated colitis in adults. Cochrane Database Syst Rev 2008; :CD004611 Metaanalysis Systematic review 6
Clostridium difficile and probiotics Hickson, M, D'Souza, AL, Muthu, N, et al. Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 2007; 335:80 Randomized clinical trial McFarland, LV, Surawicz, CM, Greenberg, RN, et al. A randomized placebo-controlled trial of Saccharomyces boulardii in combination with standard antibiotics for Clostridium difficile disease. JAMA 1994; 271:1913 Randomized controlled study Clostridium difficile and probiotics Surawicz, CM, McFarland, LV, Greenberg, RN, et al. The search for a better treatment for recurrent Clostridium difficile disease: use of high-dose vancomycin combined with Saccharomyces boulardii. Clin Infect Dis 2000; 31:1012 Randomized controlled study 7
Potential Clinical Indications for Prebiotic and Probiotic Use, From: Rakel: Integrative Medicine, 2nd ed.; chapter 104 - Prescribing Probiotics MD Consult MD Consult Conditions for which data suggest probiotics have benefit: treatment of recurrent Clostridium difficile infection Cautions needed in following settings: Immunocompromised patients Premature infants Patients with central venous access in place Untested strains 8
Approach to Management of Recurrent Clostridium difficile Diarrhea and Colitis, From: Feldman: Sleisenger & Fordtran's Gastrointestinal and Liver Disease, 8th ed.; CHAPTER 105 MD Consult 9
Primary Database Pubmed Keywords Keywords All Review clostridium difficile AND probiotics AND meta-analys* 11 8 clostridium difficile AND probiotics 181 86 10
Role of probiotics in antibiotic-associated diarrhea, Clostridium difficile-associated diarrhea, and recurrent Clostridium difficileassociated diarrhea J Clin Gastroenterol. 2008 Jul;42 Suppl 2:S64-70 Conclusion Difficulties in analysis Bacteremia and fungemia reported 60% in ICU 71% on enteral or parenteral nutrition 11
Title: Valid Results Apply to patient 問題與我的問題吻合嗎? Yes; No; can t tell 收集適當的研究設計型態的研究嗎? Yes No can t tell 值得繼續評估? Yes No 納入分析研究是否完整? Yes No can t tell 評估個體研究的有效性? Yes No can t tell 個別研究是否可以一致能整合? Yes No can t tell OR / RR 95% C.I. ARR NNT/NNH 結果運用於我的病人狀況? Yes No can t tell 結論有經過綜合性考量 (benefit/ harm/cost)? Yes No can t tell Probiotics as prevention and treatment for diarrhea Curr Opin Gastroenterol. 2009 Jan;25(1):18-23 12
Conclusion Difficulties exist to draw definite conclusions S. boulardii might be effective in treatment of CDAD S. boulardii and L. GG might be effective in treating and preventing recurrence of CDAD Resistance to antibiotics: L. reuteri ATCC 55730 and Enterococcus faecium Title: Valid Results Apply to patient 問題與我的問題吻合嗎? Yes; No; can t tell 收集適當的研究設計型態的研究嗎? Yes No can t tell 值得繼續評估? Yes No 納入分析研究是否完整? Yes No can t tell 評估個體研究的有效性? Yes No can t tell 個別研究是否可以一致能整合? Yes No can t tell OR / RR 95% C.I. ARR NNT/NNH 結果運用於我的病人狀況? Yes No can t tell 結論有經過綜合性考量 (benefit/ harm/cost)? Yes No can t tell 13
臨床應用 目前因菌種與劑量上的混亂, 造成統計不易, 針對效果的部分目前仍無定論, 可能需要規模更大的研究來針對其效果有更進一步的證據 且因為現在 probiotics 的菌種較多較為複雜, 針對 CDAD 目前認為在治療上和預防 recurrent CDAD 可能有效的菌種為 S. boulardii 和 L. GG, 但需依照目前文獻的建議劑量服用 臨床應用 安全性上原則上 probiotics 是安全的, 但仍有少數菌血症與黴菌血症的案例, 建議若是免疫力低下 近期接受過手術或有長期住院病史的患者, 或是未經證實的菌種, 要小心使用 14
Probiotics Biofermin R: Lactobacillus Shin Biofermin S: Streptococcus faecalis, B. bifidum, L. acidophilus S. boulardii: Florastor, Florastor Kid, Diarsafe Probiotics 15
去醫療化語言 目前臨床上尚無足夠證據證實有效, 部分的文獻認為若作為抗生素以外的輔助治療是有幫助的, 且可能可以預防復發 ; 原則上這些益生菌使用上是安全的, 有零星的案例有菌血症的發生, 但多是發生在免疫力低下或身體狀況較差的病人 建議我們可以先將這一次的腸子發炎治療好, 之後若有復發的情形, 在抗生素治療外可嘗試使用 Thanks for your attention! 16