Therapeutics
A microbial preparation did not reduce diarrhea in older inpatients receiving antibiotics
Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382: 1249-57.
Clinical impact ratings: h ★★★★★★✩ g ★★★★★★✩ G ★★★★★★✩ I ★★★★★★✩ Question
Conclusion
In older hospitalized patients treated with antibiotics, does a microbial preparation reduce risk for antibiotic-associated diarrhea (AAD)?
A microbial preparation did not reduce risk for antibiotic-associated diarrhea in older, hospitalized patients treated with antibiotics. *See Glossary.
Methods Design: Randomized placebo-controlled trial (PLACIDE). ISRCTN70017204. Allocation: Concealed.* Blinding: Blinded* (patients, study personnel, laboratory personnel, and data analysts). Setting: 67 surgical and medical wards in 3 hospitals in southern Wales and 2 hospitals in northeastern England, UK. Patients: 2981 inpatients ≥ 65 years of age (mean age 77 y, 50% women) who were treated with oral or IV antibiotics in the past 7 days or were about to begin antibiotic treatment. Exclusion criteria included diarrhea, need for isolation or barrier nursing due to immunocompromise, need for high-dependency or intensive care, prosthetic heart valve, Clostridium difficile diarrhea (CDD) in the past 3 months, inflammatory bowel disease needing specific treatment in the past 12 months, suspected acute pancreatitis, abnormality or disease of mesenteric vessels or celiac axis, or jejunal tube in situ or receipt of jejunal feeds. Intervention: Microbial capsule, 6 × 1010 live bacteria (2 strains of Lactobacillus acidophilus and 2 strains of bifidobacterium) (n = 1493) or placebo capsule (n = 1488), daily with food, between antibiotic doses when possible, for 21 days. Outcomes: AAD and CDD (assessed in patients with AAD) at 8 weeks. CDD was assessed in < 80% of patients with AAD and is not reported in this abstract. 2478 patients were needed to detect a 50% reduction in AAD in the microbial group (99% power, α = 0.05). Patient follow-up: 99% (modified intention-to-treat analysis).
Main results Groups did not differ for AAD at 8 weeks (Table). Microbial preparation vs placebo in older hospitalized patients treated with antibiotics† Microbial preparation
Placebo
At 8 wk
10.8%
10.4%
4% (−16 to 28) Not significant
RRI (95% CI) Antibiotic-associated diarrhea
For correspondence: Professor S. J. Allen, Swansea University, Swansea, Wales, UK. E-mail [email protected]. ■
Commentary
Follow-up period: 8 weeks.
Outcome
Sources of funding: Health Technology Assessment Programme of the National Institute for Health Research, UK, and County Durham & Tees Valley NIHR Comprehensive Local Research Network.
NNH (CI)
†Abbreviations defined in Glossary. RRI, NNH, and CI calculated from control event rate and relative risk in article.
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
AAD and CDD are common complications of antibiotic therapy in hospitalized patients. Antibiotic therapy disrupts the normal gastrointestinal microbiome, allowing C. difficile to proliferate and cause substantial morbidity and mortality. Efforts to prevent this infection have focused primarily on strategies to reduce transmission, such as hand washing and barrier precautions. However, reducing a patient’s susceptibility to infection by restoring the gastrointestinal microbiome has become a new area of research. Probiotics are nonpathogenic bacteria that help to maintain the natural balance of microflora in the gastrointestinal tract by reducing the ability of pathogenic bacteria to proliferate (1). Probiotics are commercially available as dietary supplements, and recent evidence suggests that they can prevent CDD (2). PLACIDE, the largest prospective randomized and blinded trial to date, found that probiotics do not reduce risk for AAD or CDD. The strengths of the study include the large sample size, rigorous design, and careful follow-up. A weakness of the study, which the authors acknowledge, was that the incidence of AAD and CDD was lower than predicted, and that only 93/159 patients with AAD were tested for CDD. Nonetheless, the results are compelling. It is plausible that restoring the gastrointestinal microbiome, which normally comprises hundreds of types of probiotic bacteria, will need more than just the 4 bacteria used in this study (2 strains of Lactobacillus acidophilus and 2 strains of bifidobacterium). Before a decision to change practice is made, both the efficacy of individual probiotic strains and the local incidence of CDD relative to the cost of probiotics should be considered. Marcela Ferrada, MD Naomi P. O’Grady, MD National Institutes of Health Bethesda, Maryland, USA References 1. Parkes GC, Sanderson JD, Whelan K. The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea. Lancet Infect Dis. 2009;9:237-44. 2. Johnston BC, Ma SS, Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012;157:878-88.
© 2013 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a University of California San Diego User on 06/07/2017
JC9
A microbial preparation did not reduce diarrhea in older inpatients receiving antibiotics
Allen SJ, Wareham K, Wang D, et al. Lactobacilli and bifidobacteria in the prevention of antibiotic-associated diarrhoea and Clostridium difficile diarrhoea in older inpatients (PLACIDE): a randomised, double-blind, placebo-controlled, multicentre trial. Lancet. 2013;382: 1249-57.
Clinical impact ratings: h ★★★★★★✩ g ★★★★★★✩ G ★★★★★★✩ I ★★★★★★✩ Question
Conclusion
In older hospitalized patients treated with antibiotics, does a microbial preparation reduce risk for antibiotic-associated diarrhea (AAD)?
A microbial preparation did not reduce risk for antibiotic-associated diarrhea in older, hospitalized patients treated with antibiotics. *See Glossary.
Methods Design: Randomized placebo-controlled trial (PLACIDE). ISRCTN70017204. Allocation: Concealed.* Blinding: Blinded* (patients, study personnel, laboratory personnel, and data analysts). Setting: 67 surgical and medical wards in 3 hospitals in southern Wales and 2 hospitals in northeastern England, UK. Patients: 2981 inpatients ≥ 65 years of age (mean age 77 y, 50% women) who were treated with oral or IV antibiotics in the past 7 days or were about to begin antibiotic treatment. Exclusion criteria included diarrhea, need for isolation or barrier nursing due to immunocompromise, need for high-dependency or intensive care, prosthetic heart valve, Clostridium difficile diarrhea (CDD) in the past 3 months, inflammatory bowel disease needing specific treatment in the past 12 months, suspected acute pancreatitis, abnormality or disease of mesenteric vessels or celiac axis, or jejunal tube in situ or receipt of jejunal feeds. Intervention: Microbial capsule, 6 × 1010 live bacteria (2 strains of Lactobacillus acidophilus and 2 strains of bifidobacterium) (n = 1493) or placebo capsule (n = 1488), daily with food, between antibiotic doses when possible, for 21 days. Outcomes: AAD and CDD (assessed in patients with AAD) at 8 weeks. CDD was assessed in < 80% of patients with AAD and is not reported in this abstract. 2478 patients were needed to detect a 50% reduction in AAD in the microbial group (99% power, α = 0.05). Patient follow-up: 99% (modified intention-to-treat analysis).
Main results Groups did not differ for AAD at 8 weeks (Table). Microbial preparation vs placebo in older hospitalized patients treated with antibiotics† Microbial preparation
Placebo
At 8 wk
10.8%
10.4%
4% (−16 to 28) Not significant
RRI (95% CI) Antibiotic-associated diarrhea
For correspondence: Professor S. J. Allen, Swansea University, Swansea, Wales, UK. E-mail [email protected]. ■
Commentary
Follow-up period: 8 weeks.
Outcome
Sources of funding: Health Technology Assessment Programme of the National Institute for Health Research, UK, and County Durham & Tees Valley NIHR Comprehensive Local Research Network.
NNH (CI)
†Abbreviations defined in Glossary. RRI, NNH, and CI calculated from control event rate and relative risk in article.
19 November 2013 | ACP Journal Club | Volume 159 • Number 10
AAD and CDD are common complications of antibiotic therapy in hospitalized patients. Antibiotic therapy disrupts the normal gastrointestinal microbiome, allowing C. difficile to proliferate and cause substantial morbidity and mortality. Efforts to prevent this infection have focused primarily on strategies to reduce transmission, such as hand washing and barrier precautions. However, reducing a patient’s susceptibility to infection by restoring the gastrointestinal microbiome has become a new area of research. Probiotics are nonpathogenic bacteria that help to maintain the natural balance of microflora in the gastrointestinal tract by reducing the ability of pathogenic bacteria to proliferate (1). Probiotics are commercially available as dietary supplements, and recent evidence suggests that they can prevent CDD (2). PLACIDE, the largest prospective randomized and blinded trial to date, found that probiotics do not reduce risk for AAD or CDD. The strengths of the study include the large sample size, rigorous design, and careful follow-up. A weakness of the study, which the authors acknowledge, was that the incidence of AAD and CDD was lower than predicted, and that only 93/159 patients with AAD were tested for CDD. Nonetheless, the results are compelling. It is plausible that restoring the gastrointestinal microbiome, which normally comprises hundreds of types of probiotic bacteria, will need more than just the 4 bacteria used in this study (2 strains of Lactobacillus acidophilus and 2 strains of bifidobacterium). Before a decision to change practice is made, both the efficacy of individual probiotic strains and the local incidence of CDD relative to the cost of probiotics should be considered. Marcela Ferrada, MD Naomi P. O’Grady, MD National Institutes of Health Bethesda, Maryland, USA References 1. Parkes GC, Sanderson JD, Whelan K. The mechanisms and efficacy of probiotics in the prevention of Clostridium difficile-associated diarrhoea. Lancet Infect Dis. 2009;9:237-44. 2. Johnston BC, Ma SS, Goldenberg JZ, et al. Probiotics for the prevention of Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. Ann Intern Med. 2012;157:878-88.
© 2013 American College of Physicians
Downloaded From: http://annals.org/pdfaccess.ashx?url=/data/journals/aim/928838/ by a University of California San Diego User on 06/07/2017
JC9
