Karli Edholm, MD

Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?

Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.

Study design: Noninferiority, randomized clinical trial.

Setting: Six hospitals in Finland.

Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.

Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.

Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.

Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348

Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?

Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.

Study design: Noninferiority, randomized clinical trial.

Setting: Six hospitals in Finland.

Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.

Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.

Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.

Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348

Clinical question: Is antibiotic therapy noninferior to appendectomy for treatment of uncomplicated acute appendicitis?

Background: Previous randomized clinical trials have compared antibiotic therapy versus appendectomy for the treatment of uncomplicated, acute appendicitis. Each of these studies had significant limitations, and appendectomy has remained the standard of care.

Study design: Noninferiority, randomized clinical trial.

Setting: Six hospitals in Finland.

Synopsis: Investigators randomized 530 patients with uncomplicated appendicitis confirmed on CT to appendectomy or antibiotic therapy, with a noninferiority margin of 24%. Of the 256 patients randomized to antibiotics who were available for follow-up, 70 received surgical intervention within one year. This resulted in a difference between treatment groups of -27%. Further analysis revealed that five of those patients had normal appendices and did not actually require appendectomy. Secondary outcome analysis demonstrated a significantly lower complication rate among patients in the antibiotic group (2.8%) compared with the surgical group (20.5%); however, the open operative approach used on most patients may have resulted in increased wound complications.

Although noninferiority of antibiotic treatment was not demonstrated, the majority of patients in the antibiotic group (73%) were found to have successful treatment with antibiotics alone. None of these patients, including those eventually undergoing appendectomy, suffered major complications. Although the overall approach to uncomplicated appendicitis may not change, physicians and patients should utilize this data to make an informed decision between antibiotic treatment and appendectomy.

Bottom line: In patients with CT-proven, uncomplicated acute appendicitis, antibiotic treatment did not meet the pre-specified threshold for noninferiority compared with appendectomy, yet a significant majority of patients in the antibiotic arm had successful recovery.

Citation: Salminen P, Paajanen H, Rautio T, et al. Antibiotic therapy vs appendectomy for treatment of uncomplicated acute appendicitis: The APPAC randomized clinical trial. JAMA. 2015;313(23):2340-2348

Clinical question: Why do healthcare providers work while sick?

Background: Healthcare providers generally are aware of the risks of infection to hospitalized patients; however, despite this knowledge, several studies have revealed providers continue to work while ill.

Study design: Mixed-method analysis of a cross-sectional survey.

Setting: Large academic children’s hospital.

Synopsis: Investigators completed 538 of 929 surveys of attending physicians and advanced practice clinicians (APCs), a response rate of 58%. Of the respondents, 95% agreed that sick providers continuing patient care increased their patients’ risk for infection; however, 83% admitted to caring for patients while sick, with physicians being more likely to do so.

Several factors contributed to this behavior, including fear of letting colleagues or patients down, fear of ostracism by colleagues, and concerns for understaffing or discontinuity of care. Qualitative analysis of free-text responses revealed additional factors, including the difficulty of finding sick coverage, the strong cultural norms to continue working unless severely ill, and the ambiguity of defining “too sick to work.”

Limitations of this study included possible response bias, lack of a validated survey, and inclusion of only a single center; however, results confirm prior studies and reveal additional systems factors that hospital leadership could address, supporting providers and improving patient care.

Bottom line: Sick healthcare providers face several challenges that drive them to put their patients at risk by continuing patient care, and these factors could be addressed by healthcare systems as a means of improving overall quality of care.

Citation: Szymczak JE, Smathers S, Hoegg C, Klieger S, Coffin SE, Sammons JS. Reasons why physicians and advanced practice clinicians work while sick: a mixed-methods analysis. JAMA Pediatr. 2015;169(9):815-821. doi:10.1001/jamapediatrics.2015.0684.

Clinical question: Why do healthcare providers work while sick?

Background: Healthcare providers generally are aware of the risks of infection to hospitalized patients; however, despite this knowledge, several studies have revealed providers continue to work while ill.

Study design: Mixed-method analysis of a cross-sectional survey.

Setting: Large academic children’s hospital.

Synopsis: Investigators completed 538 of 929 surveys of attending physicians and advanced practice clinicians (APCs), a response rate of 58%. Of the respondents, 95% agreed that sick providers continuing patient care increased their patients’ risk for infection; however, 83% admitted to caring for patients while sick, with physicians being more likely to do so.

Several factors contributed to this behavior, including fear of letting colleagues or patients down, fear of ostracism by colleagues, and concerns for understaffing or discontinuity of care. Qualitative analysis of free-text responses revealed additional factors, including the difficulty of finding sick coverage, the strong cultural norms to continue working unless severely ill, and the ambiguity of defining “too sick to work.”

Limitations of this study included possible response bias, lack of a validated survey, and inclusion of only a single center; however, results confirm prior studies and reveal additional systems factors that hospital leadership could address, supporting providers and improving patient care.

Bottom line: Sick healthcare providers face several challenges that drive them to put their patients at risk by continuing patient care, and these factors could be addressed by healthcare systems as a means of improving overall quality of care.

Citation: Szymczak JE, Smathers S, Hoegg C, Klieger S, Coffin SE, Sammons JS. Reasons why physicians and advanced practice clinicians work while sick: a mixed-methods analysis. JAMA Pediatr. 2015;169(9):815-821. doi:10.1001/jamapediatrics.2015.0684.

Clinical question: Why do healthcare providers work while sick?

Background: Healthcare providers generally are aware of the risks of infection to hospitalized patients; however, despite this knowledge, several studies have revealed providers continue to work while ill.

Study design: Mixed-method analysis of a cross-sectional survey.

Setting: Large academic children’s hospital.

Synopsis: Investigators completed 538 of 929 surveys of attending physicians and advanced practice clinicians (APCs), a response rate of 58%. Of the respondents, 95% agreed that sick providers continuing patient care increased their patients’ risk for infection; however, 83% admitted to caring for patients while sick, with physicians being more likely to do so.

Several factors contributed to this behavior, including fear of letting colleagues or patients down, fear of ostracism by colleagues, and concerns for understaffing or discontinuity of care. Qualitative analysis of free-text responses revealed additional factors, including the difficulty of finding sick coverage, the strong cultural norms to continue working unless severely ill, and the ambiguity of defining “too sick to work.”

Limitations of this study included possible response bias, lack of a validated survey, and inclusion of only a single center; however, results confirm prior studies and reveal additional systems factors that hospital leadership could address, supporting providers and improving patient care.

Bottom line: Sick healthcare providers face several challenges that drive them to put their patients at risk by continuing patient care, and these factors could be addressed by healthcare systems as a means of improving overall quality of care.

Citation: Szymczak JE, Smathers S, Hoegg C, Klieger S, Coffin SE, Sammons JS. Reasons why physicians and advanced practice clinicians work while sick: a mixed-methods analysis. JAMA Pediatr. 2015;169(9):815-821. doi:10.1001/jamapediatrics.2015.0684.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary-care hospitals in Switzerland.

Synopsis: A group of 784 patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33; 95% CI, 1.15–1.50, P <0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin. Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–1518.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary-care hospitals in Switzerland.

Synopsis: A group of 784 patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33; 95% CI, 1.15–1.50, P <0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin. Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–1518.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary-care hospitals in Switzerland.

Synopsis: A group of 784 patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33; 95% CI, 1.15–1.50, P <0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin. Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511–1518.

Clinical question: What risk factors predict septic arthritis surgical debridement failure?

Background: Standard treatment of septic arthritis is debridement and antibiotics. Unfortunately, 23%-48% of patients fail single debridement. Data is limited on what factors correlate with treatment failure.

Study design: Retrospective, logistic regression analysis.

Setting: Billing database query of one academic medical center from 2000-2011.

Synopsis: After excluding patients with orthopedic comorbidities, multivariate logistic regression was performed on 128 patients greater than 18 years of age and treated operatively for septic arthritis, 38% of whom had failed a single debridement. Five significant independent clinical variables were identified as predictors for failure of a single surgical debridement:

• History of inflammatory arthropathy (OR, 7.3; 95% CI, 2.4 to 22.6; P<0.001);
• Involvement of a large joint (knee, shoulder, or hip; OR 7.0; 95% CI, 1.2-37.5; P=0.02);
• Synovial fluid nucleated cell count >85.0 x 109 cells/L (OR, 4.7; 95% CI, 1.8-17.7; P=0.002);
• S. aureus as an isolate (OR, 4.6; 95% CI, 1.8 to 11.9; P=0.002); and
• History of diabetes (OR, 2.6; 95% CI, 1.1 to 6.2; P=0.04).

Using these variables, a prognostic model was created with an ROC curve of 0.79.

The study’s limitations include its retrospective nature, reliance on coding and documentation, small sample size, and the fact that all patients were treated at a single center.

Bottom line: Risk factors for failing single debridement in septic arthritis include inflammatory arthropathy, large joint involvement, more than 85.0 x 109 nucleated cells, S. aureus infection, and history of diabetes.

Citation: Hunter JG, Gross JM, Dahl JD, Amsdell SL, Gorczyca JT. Risk factors for failure of a single surgical debridement in adults with acute septic arthritis. J Bone Joint Surg Am. 2015;97(7):558-564.

Clinical question: What risk factors predict septic arthritis surgical debridement failure?

Background: Standard treatment of septic arthritis is debridement and antibiotics. Unfortunately, 23%-48% of patients fail single debridement. Data is limited on what factors correlate with treatment failure.

Study design: Retrospective, logistic regression analysis.

Setting: Billing database query of one academic medical center from 2000-2011.

Synopsis: After excluding patients with orthopedic comorbidities, multivariate logistic regression was performed on 128 patients greater than 18 years of age and treated operatively for septic arthritis, 38% of whom had failed a single debridement. Five significant independent clinical variables were identified as predictors for failure of a single surgical debridement:

• History of inflammatory arthropathy (OR, 7.3; 95% CI, 2.4 to 22.6; P<0.001);
• Involvement of a large joint (knee, shoulder, or hip; OR 7.0; 95% CI, 1.2-37.5; P=0.02);
• Synovial fluid nucleated cell count >85.0 x 109 cells/L (OR, 4.7; 95% CI, 1.8-17.7; P=0.002);
• S. aureus as an isolate (OR, 4.6; 95% CI, 1.8 to 11.9; P=0.002); and
• History of diabetes (OR, 2.6; 95% CI, 1.1 to 6.2; P=0.04).

Using these variables, a prognostic model was created with an ROC curve of 0.79.

The study’s limitations include its retrospective nature, reliance on coding and documentation, small sample size, and the fact that all patients were treated at a single center.

Bottom line: Risk factors for failing single debridement in septic arthritis include inflammatory arthropathy, large joint involvement, more than 85.0 x 109 nucleated cells, S. aureus infection, and history of diabetes.

Citation: Hunter JG, Gross JM, Dahl JD, Amsdell SL, Gorczyca JT. Risk factors for failure of a single surgical debridement in adults with acute septic arthritis. J Bone Joint Surg Am. 2015;97(7):558-564.

Clinical question: What risk factors predict septic arthritis surgical debridement failure?

Background: Standard treatment of septic arthritis is debridement and antibiotics. Unfortunately, 23%-48% of patients fail single debridement. Data is limited on what factors correlate with treatment failure.

Study design: Retrospective, logistic regression analysis.

Setting: Billing database query of one academic medical center from 2000-2011.

Synopsis: After excluding patients with orthopedic comorbidities, multivariate logistic regression was performed on 128 patients greater than 18 years of age and treated operatively for septic arthritis, 38% of whom had failed a single debridement. Five significant independent clinical variables were identified as predictors for failure of a single surgical debridement:

• History of inflammatory arthropathy (OR, 7.3; 95% CI, 2.4 to 22.6; P<0.001);
• Involvement of a large joint (knee, shoulder, or hip; OR 7.0; 95% CI, 1.2-37.5; P=0.02);
• Synovial fluid nucleated cell count >85.0 x 109 cells/L (OR, 4.7; 95% CI, 1.8-17.7; P=0.002);
• S. aureus as an isolate (OR, 4.6; 95% CI, 1.8 to 11.9; P=0.002); and
• History of diabetes (OR, 2.6; 95% CI, 1.1 to 6.2; P=0.04).

Using these variables, a prognostic model was created with an ROC curve of 0.79.

The study’s limitations include its retrospective nature, reliance on coding and documentation, small sample size, and the fact that all patients were treated at a single center.

Bottom line: Risk factors for failing single debridement in septic arthritis include inflammatory arthropathy, large joint involvement, more than 85.0 x 109 nucleated cells, S. aureus infection, and history of diabetes.

Citation: Hunter JG, Gross JM, Dahl JD, Amsdell SL, Gorczyca JT. Risk factors for failure of a single surgical debridement in adults with acute septic arthritis. J Bone Joint Surg Am. 2015;97(7):558-564.

Clinical question: Does administration of prednisolone or pentoxifylline reduce mortality in patients hospitalized with severe alcoholic hepatitis?

Background: Alcoholic hepatitis is associated with high mortality. Studies have shown unclear mortality benefit with prednisolone and pentoxifylline. Despite multiple studies and meta-analyses, controversy about the use of these medications persists.

Study Design: Multicenter, double-blind, randomized trial with 2-by-2 design.

Setting: Sixty-five hospitals across the United Kingdom.

Synopsis: Approximately 1,100 patients with a clinical diagnosis of alcoholic hepatitis were randomized to four groups: placebo + placebo; prednisolone + pentoxifylline-matched placebo; prednisolone-matched placebo + pentoxifylline; or prednisolone + pentoxifylline. Groups received 28 days of treatment. The primary endpoint was 28-day mortality. Secondary endpoints were mortality or liver transplantation at 90 days and one year.

Neither intervention showed a significant reduction in 28-day mortality. Secondary analysis with adjustments for risk showed a reduction in 28-day mortality in the prednisolone groups. There was no difference between groups for mortality or liver transplantation at 90 days or one year.

Adverse events of death, infection, and acute kidney injury were reported in 42% of patients. Infection rates were higher in the prednisolone groups; however, attributable deaths were no different between groups.

Patients in this trial were younger, with a lower incidence of encephalopathy, infection, and acute kidney injury than those seen in similar trials, which could affect the rates of mortality seen here. Also, liver biopsy was not used, so patients may have been incorrectly included.

Bottom line: No difference was found in mortality or liver transplantation at 90 days and one year for prednisolone or pentoxifylline, although subanalysis showed there may be short-term benefit with prednisolone.

Citation: Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. New Engl J Med. 2015;372(17):1619-1628.

Clinical question: Does administration of prednisolone or pentoxifylline reduce mortality in patients hospitalized with severe alcoholic hepatitis?

Background: Alcoholic hepatitis is associated with high mortality. Studies have shown unclear mortality benefit with prednisolone and pentoxifylline. Despite multiple studies and meta-analyses, controversy about the use of these medications persists.

Study Design: Multicenter, double-blind, randomized trial with 2-by-2 design.

Setting: Sixty-five hospitals across the United Kingdom.

Synopsis: Approximately 1,100 patients with a clinical diagnosis of alcoholic hepatitis were randomized to four groups: placebo + placebo; prednisolone + pentoxifylline-matched placebo; prednisolone-matched placebo + pentoxifylline; or prednisolone + pentoxifylline. Groups received 28 days of treatment. The primary endpoint was 28-day mortality. Secondary endpoints were mortality or liver transplantation at 90 days and one year.

Neither intervention showed a significant reduction in 28-day mortality. Secondary analysis with adjustments for risk showed a reduction in 28-day mortality in the prednisolone groups. There was no difference between groups for mortality or liver transplantation at 90 days or one year.

Adverse events of death, infection, and acute kidney injury were reported in 42% of patients. Infection rates were higher in the prednisolone groups; however, attributable deaths were no different between groups.

Patients in this trial were younger, with a lower incidence of encephalopathy, infection, and acute kidney injury than those seen in similar trials, which could affect the rates of mortality seen here. Also, liver biopsy was not used, so patients may have been incorrectly included.

Bottom line: No difference was found in mortality or liver transplantation at 90 days and one year for prednisolone or pentoxifylline, although subanalysis showed there may be short-term benefit with prednisolone.

Citation: Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. New Engl J Med. 2015;372(17):1619-1628.

Clinical question: Does administration of prednisolone or pentoxifylline reduce mortality in patients hospitalized with severe alcoholic hepatitis?

Background: Alcoholic hepatitis is associated with high mortality. Studies have shown unclear mortality benefit with prednisolone and pentoxifylline. Despite multiple studies and meta-analyses, controversy about the use of these medications persists.

Study Design: Multicenter, double-blind, randomized trial with 2-by-2 design.

Setting: Sixty-five hospitals across the United Kingdom.

Synopsis: Approximately 1,100 patients with a clinical diagnosis of alcoholic hepatitis were randomized to four groups: placebo + placebo; prednisolone + pentoxifylline-matched placebo; prednisolone-matched placebo + pentoxifylline; or prednisolone + pentoxifylline. Groups received 28 days of treatment. The primary endpoint was 28-day mortality. Secondary endpoints were mortality or liver transplantation at 90 days and one year.

Neither intervention showed a significant reduction in 28-day mortality. Secondary analysis with adjustments for risk showed a reduction in 28-day mortality in the prednisolone groups. There was no difference between groups for mortality or liver transplantation at 90 days or one year.

Adverse events of death, infection, and acute kidney injury were reported in 42% of patients. Infection rates were higher in the prednisolone groups; however, attributable deaths were no different between groups.

Patients in this trial were younger, with a lower incidence of encephalopathy, infection, and acute kidney injury than those seen in similar trials, which could affect the rates of mortality seen here. Also, liver biopsy was not used, so patients may have been incorrectly included.

Bottom line: No difference was found in mortality or liver transplantation at 90 days and one year for prednisolone or pentoxifylline, although subanalysis showed there may be short-term benefit with prednisolone.

Citation: Thursz MR, Richardson P, Allison M, et al. Prednisolone or pentoxifylline for alcoholic hepatitis. New Engl J Med. 2015;372(17):1619-1628.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary care hospitals in Switzerland.

Synopsis: Seven hundred eighty-four patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33, 95% CI 1.15-1.50, P<0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin.

Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicenter, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511-1518.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary care hospitals in Switzerland.

Synopsis: Seven hundred eighty-four patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33, 95% CI 1.15-1.50, P<0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin.

Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicenter, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511-1518.

Clinical question: Does corticosteroid treatment shorten systemic illness in patients admitted to the hospital for community-acquired pneumonia (CAP)?

Background: Pneumonia is the third-leading cause of death worldwide. Studies have yielded conflicting data about the benefit of adding systemic corticosteroids for treatment of CAP.

Study design: Double-blind, multicenter, randomized, placebo-controlled trial.

Setting: Seven tertiary care hospitals in Switzerland.

Synopsis: Seven hundred eighty-four patients hospitalized for CAP were randomized to receive either oral prednisone 50 mg daily for seven days or placebo, with the primary endpoint being time to stable vital signs. The intention-to-treat analysis found that the median time to clinical stability was 1.4 days earlier in the prednisone group (hazard ratio 1.33, 95% CI 1.15-1.50, P<0.0001) and that length of stay and IV antibiotics were reduced by one day; this effect was valid across all PSI classes and was not dependent on age. Pneumonia-associated complications in the two groups did not differ at 30 days, though the prednisone group had a higher incidence of hyperglycemia requiring insulin.

Because all study locations were in a single, fairly homogenous northern European country, care should be taken when hospitalists apply these findings to their patient population, and the risks of hyperglycemia requiring insulin should be taken into consideration.

Bottom line: Systemic steroids may reduce the time to clinical stability in patients with CAP.

Citation: Blum CA, Nigro N, Briel M, et al. Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicenter, double-blind, randomised, placebo-controlled trial. Lancet. 2015;385(9977):1511-1518.

Clinical question: Can a nomogram accurately predict a patient’s risk of post-operative 30-day readmission?

Background: Medicare and Medicaid have implemented penalties for hospitals with high readmission rates. While this does not yet apply to post-operative readmissions, there is concern that it soon will. Algorithms for predicting readmission have been developed for medical patients; however, to date, no such tool has been developed for post-operative patients.

Study design: Retrospective review and prospective validation of a predictive nomogram.

Setting: Single academic hospital.

Synopsis: Using the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) and hospital billing data, a retrospective analysis of 2,799 patients who had elective surgery between 2006 and 2011 was performed in order to develop a predictive nomogram for post-operative readmissions. Pre-operative, operative, and post-operative variables associated with readmission were evaluated, and the following variables were found to be independently associated with readmission:

• Bleeding disorder;
• Prolonged procedure length;
• In-hospital complications;
• Dependent functional status; and/or
• Higher care at discharge.

Using a linear regression model, a nomogram was developed that was prospectively validated in 255 patients from a single center. The nomogram accurately predicted the risk of post-operative readmission (C statistic=0.756) in the prospective analysis.

The nomogram has limited generalizability given the fact that it included patients from a single institution; it would benefit from external validation before widespread use.

Bottom line: The use of this predictive nomogram could aid in identifying patients at high risk of readmission.

Citation: Tevis SE, Weber SM, Kent KC, Kennedy GD. Nomogram to predict postoperative readmission in patients who undergo general surgery. JAMA Surg. 2015;150(6):505-510. doi: 10.1001/jamasurg.2014.4043.

Clinical question: Can a nomogram accurately predict a patient’s risk of post-operative 30-day readmission?

Background: Medicare and Medicaid have implemented penalties for hospitals with high readmission rates. While this does not yet apply to post-operative readmissions, there is concern that it soon will. Algorithms for predicting readmission have been developed for medical patients; however, to date, no such tool has been developed for post-operative patients.

Study design: Retrospective review and prospective validation of a predictive nomogram.

Setting: Single academic hospital.

Synopsis: Using the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) and hospital billing data, a retrospective analysis of 2,799 patients who had elective surgery between 2006 and 2011 was performed in order to develop a predictive nomogram for post-operative readmissions. Pre-operative, operative, and post-operative variables associated with readmission were evaluated, and the following variables were found to be independently associated with readmission:

• Bleeding disorder;
• Prolonged procedure length;
• In-hospital complications;
• Dependent functional status; and/or
• Higher care at discharge.

Using a linear regression model, a nomogram was developed that was prospectively validated in 255 patients from a single center. The nomogram accurately predicted the risk of post-operative readmission (C statistic=0.756) in the prospective analysis.

The nomogram has limited generalizability given the fact that it included patients from a single institution; it would benefit from external validation before widespread use.

Bottom line: The use of this predictive nomogram could aid in identifying patients at high risk of readmission.

Citation: Tevis SE, Weber SM, Kent KC, Kennedy GD. Nomogram to predict postoperative readmission in patients who undergo general surgery. JAMA Surg. 2015;150(6):505-510. doi: 10.1001/jamasurg.2014.4043.

Clinical question: Can a nomogram accurately predict a patient’s risk of post-operative 30-day readmission?

Background: Medicare and Medicaid have implemented penalties for hospitals with high readmission rates. While this does not yet apply to post-operative readmissions, there is concern that it soon will. Algorithms for predicting readmission have been developed for medical patients; however, to date, no such tool has been developed for post-operative patients.

Study design: Retrospective review and prospective validation of a predictive nomogram.

Setting: Single academic hospital.

Synopsis: Using the American College of Surgeons’ National Surgical Quality Improvement Program (ACS NSQIP) and hospital billing data, a retrospective analysis of 2,799 patients who had elective surgery between 2006 and 2011 was performed in order to develop a predictive nomogram for post-operative readmissions. Pre-operative, operative, and post-operative variables associated with readmission were evaluated, and the following variables were found to be independently associated with readmission:

• Bleeding disorder;
• Prolonged procedure length;
• In-hospital complications;
• Dependent functional status; and/or
• Higher care at discharge.

Using a linear regression model, a nomogram was developed that was prospectively validated in 255 patients from a single center. The nomogram accurately predicted the risk of post-operative readmission (C statistic=0.756) in the prospective analysis.

The nomogram has limited generalizability given the fact that it included patients from a single institution; it would benefit from external validation before widespread use.

Bottom line: The use of this predictive nomogram could aid in identifying patients at high risk of readmission.

Citation: Tevis SE, Weber SM, Kent KC, Kennedy GD. Nomogram to predict postoperative readmission in patients who undergo general surgery. JAMA Surg. 2015;150(6):505-510. doi: 10.1001/jamasurg.2014.4043.

Clinical question: What are the updated recommendations for treating first unprovoked seizure in adults?

Background: Approximately 150,000 adults present with an unprovoked first seizure in the U.S. annually, and these events are associated with physical and psychological trauma. Prior guidelines discussed evaluation of unprovoked first seizures in adults but did not address management. This publication aims to analyze existing evidence regarding prognosis and therapy with antiepileptic drugs (AEDs).

Study design: Evidence-based appraisal of a systematic review.

Setting: Literature published from 1966 to 2013 on MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.

Synopsis: Ten prognostic studies describing risk of recurrence were found. Generalized tonic-clonic seizures were the major seizure type. Cumulative incidence of recurrent seizure increased over time, with the majority occurring within the first two years, regardless of treatment with AED; however, there were treatment differences among these studies and wide variation in recurrence rates.

Recurrence risk was lower with AED therapy, though patients were not randomized. Increased risk of recurrence was associated with prior brain lesion causing the seizure, EEG with epileptiform abnormalities, imaging abnormality, and nocturnal seizure.

Five studies were reviewed for prognosis following immediate AED therapy. Immediate AED treatment reduced risk of recurrence by 35% over the first two years. Among studies, “immediate” ranged from within one week to up to three months. Two studies described long-term prognosis, concluding that immediate AED treatment was unlikely to improve the chance of sustained seizure remission.

Five studies were used to describe adverse events in patients treated with AED. Adverse event incidence varied from 7% to 31%, and the incidents that occurred were largely mild and were reversible.

Bottom line: In adults presenting with unprovoked first seizure, the risk of recurrence is highest in the first two years and can be reduced with immediate AED therapy, though AED therapy was not shown to improve long-term prognosis.

Citation: Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84(16):1705-1713.

Clinical question: What are the updated recommendations for treating first unprovoked seizure in adults?

Background: Approximately 150,000 adults present with an unprovoked first seizure in the U.S. annually, and these events are associated with physical and psychological trauma. Prior guidelines discussed evaluation of unprovoked first seizures in adults but did not address management. This publication aims to analyze existing evidence regarding prognosis and therapy with antiepileptic drugs (AEDs).

Study design: Evidence-based appraisal of a systematic review.

Setting: Literature published from 1966 to 2013 on MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.

Synopsis: Ten prognostic studies describing risk of recurrence were found. Generalized tonic-clonic seizures were the major seizure type. Cumulative incidence of recurrent seizure increased over time, with the majority occurring within the first two years, regardless of treatment with AED; however, there were treatment differences among these studies and wide variation in recurrence rates.

Recurrence risk was lower with AED therapy, though patients were not randomized. Increased risk of recurrence was associated with prior brain lesion causing the seizure, EEG with epileptiform abnormalities, imaging abnormality, and nocturnal seizure.

Five studies were reviewed for prognosis following immediate AED therapy. Immediate AED treatment reduced risk of recurrence by 35% over the first two years. Among studies, “immediate” ranged from within one week to up to three months. Two studies described long-term prognosis, concluding that immediate AED treatment was unlikely to improve the chance of sustained seizure remission.

Five studies were used to describe adverse events in patients treated with AED. Adverse event incidence varied from 7% to 31%, and the incidents that occurred were largely mild and were reversible.

Bottom line: In adults presenting with unprovoked first seizure, the risk of recurrence is highest in the first two years and can be reduced with immediate AED therapy, though AED therapy was not shown to improve long-term prognosis.

Citation: Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84(16):1705-1713.

Clinical question: What are the updated recommendations for treating first unprovoked seizure in adults?

Background: Approximately 150,000 adults present with an unprovoked first seizure in the U.S. annually, and these events are associated with physical and psychological trauma. Prior guidelines discussed evaluation of unprovoked first seizures in adults but did not address management. This publication aims to analyze existing evidence regarding prognosis and therapy with antiepileptic drugs (AEDs).

Study design: Evidence-based appraisal of a systematic review.

Setting: Literature published from 1966 to 2013 on MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials.

Synopsis: Ten prognostic studies describing risk of recurrence were found. Generalized tonic-clonic seizures were the major seizure type. Cumulative incidence of recurrent seizure increased over time, with the majority occurring within the first two years, regardless of treatment with AED; however, there were treatment differences among these studies and wide variation in recurrence rates.

Recurrence risk was lower with AED therapy, though patients were not randomized. Increased risk of recurrence was associated with prior brain lesion causing the seizure, EEG with epileptiform abnormalities, imaging abnormality, and nocturnal seizure.

Five studies were reviewed for prognosis following immediate AED therapy. Immediate AED treatment reduced risk of recurrence by 35% over the first two years. Among studies, “immediate” ranged from within one week to up to three months. Two studies described long-term prognosis, concluding that immediate AED treatment was unlikely to improve the chance of sustained seizure remission.

Five studies were used to describe adverse events in patients treated with AED. Adverse event incidence varied from 7% to 31%, and the incidents that occurred were largely mild and were reversible.

Bottom line: In adults presenting with unprovoked first seizure, the risk of recurrence is highest in the first two years and can be reduced with immediate AED therapy, though AED therapy was not shown to improve long-term prognosis.

Citation: Krumholz A, Wiebe S, Gronseth GS, et al. Evidence-based guideline: management of an unprovoked first seizure in adults. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the American Epilepsy Society. Neurology. 2015;84(16):1705-1713.

Clinical question: What are the risk factors for development of a recurrent infection in cirrhotic patients hospitalized with an initial infection?

Background: Infections are a major cause of morbidity and mortality in patients with cirrhosis. Prior retrospective data suggest that proton pump inhibitors (PPIs) increase the risk of infections in cirrhotic patients, while beta blockers do not. This study sought to prospectively evaluate risk factors for recurrent infections in hospitalized patients with cirrhosis.

Study design: Prospective, multicenter study.

Setting: Twelve North American hospitalists enrolled in the North American Consortium for the Study of End-Stage Liver Disease.

Synopsis: Researchers enrolled 188 hospitalized cirrhotic patients who had or developed an infection during their hospitalization. Patients were followed for six months to determine risk of development of subsequent infection and to identify independent risk factors associated with recurrent infections.

Forty-five percent of patients developed a subsequent infection, 74% of which occurred in a different location than the primary infection. This risk was independent of liver disease severity.

Age (OR 1.06; CI 1.02-1.11), PPI use (OR 2.72; CI 1.30-5.71), and spontaneous bacterial peritonitis (SBP) prophylaxis (OR 3.66; CI 1.60-8.37) were found to be independent predictors of recurrent infections. Beta blocker use did not differ between those who developed an infection and those who did not. An initial infection of SBP (compared to other infection sites) was protective (OR 0.37; CI 0.15-0.91) against subsequent infection.

Notably, study size was small, and 18% of patients were lost to follow-up. Further studies are needed to determine effective strategies to prevent recurrent infections in cirrhotics.

Bottom line: Cirrhotic patients hospitalized with an infection are at high risk of recurrent infections, and the long-term use of SBP prophylaxis and PPIs independently increase this risk.

Citation: O’Leary JG, Reddy KR, Wong F, et al. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. Clinical Gastro Hepatol. 2015;13(4):753-759.

Clinical question: What are the risk factors for development of a recurrent infection in cirrhotic patients hospitalized with an initial infection?

Background: Infections are a major cause of morbidity and mortality in patients with cirrhosis. Prior retrospective data suggest that proton pump inhibitors (PPIs) increase the risk of infections in cirrhotic patients, while beta blockers do not. This study sought to prospectively evaluate risk factors for recurrent infections in hospitalized patients with cirrhosis.

Study design: Prospective, multicenter study.

Setting: Twelve North American hospitalists enrolled in the North American Consortium for the Study of End-Stage Liver Disease.

Synopsis: Researchers enrolled 188 hospitalized cirrhotic patients who had or developed an infection during their hospitalization. Patients were followed for six months to determine risk of development of subsequent infection and to identify independent risk factors associated with recurrent infections.

Forty-five percent of patients developed a subsequent infection, 74% of which occurred in a different location than the primary infection. This risk was independent of liver disease severity.

Age (OR 1.06; CI 1.02-1.11), PPI use (OR 2.72; CI 1.30-5.71), and spontaneous bacterial peritonitis (SBP) prophylaxis (OR 3.66; CI 1.60-8.37) were found to be independent predictors of recurrent infections. Beta blocker use did not differ between those who developed an infection and those who did not. An initial infection of SBP (compared to other infection sites) was protective (OR 0.37; CI 0.15-0.91) against subsequent infection.

Notably, study size was small, and 18% of patients were lost to follow-up. Further studies are needed to determine effective strategies to prevent recurrent infections in cirrhotics.

Bottom line: Cirrhotic patients hospitalized with an infection are at high risk of recurrent infections, and the long-term use of SBP prophylaxis and PPIs independently increase this risk.

Citation: O’Leary JG, Reddy KR, Wong F, et al. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. Clinical Gastro Hepatol. 2015;13(4):753-759.

Clinical question: What are the risk factors for development of a recurrent infection in cirrhotic patients hospitalized with an initial infection?

Background: Infections are a major cause of morbidity and mortality in patients with cirrhosis. Prior retrospective data suggest that proton pump inhibitors (PPIs) increase the risk of infections in cirrhotic patients, while beta blockers do not. This study sought to prospectively evaluate risk factors for recurrent infections in hospitalized patients with cirrhosis.

Study design: Prospective, multicenter study.

Setting: Twelve North American hospitalists enrolled in the North American Consortium for the Study of End-Stage Liver Disease.

Synopsis: Researchers enrolled 188 hospitalized cirrhotic patients who had or developed an infection during their hospitalization. Patients were followed for six months to determine risk of development of subsequent infection and to identify independent risk factors associated with recurrent infections.

Forty-five percent of patients developed a subsequent infection, 74% of which occurred in a different location than the primary infection. This risk was independent of liver disease severity.

Age (OR 1.06; CI 1.02-1.11), PPI use (OR 2.72; CI 1.30-5.71), and spontaneous bacterial peritonitis (SBP) prophylaxis (OR 3.66; CI 1.60-8.37) were found to be independent predictors of recurrent infections. Beta blocker use did not differ between those who developed an infection and those who did not. An initial infection of SBP (compared to other infection sites) was protective (OR 0.37; CI 0.15-0.91) against subsequent infection.

Notably, study size was small, and 18% of patients were lost to follow-up. Further studies are needed to determine effective strategies to prevent recurrent infections in cirrhotics.

Bottom line: Cirrhotic patients hospitalized with an infection are at high risk of recurrent infections, and the long-term use of SBP prophylaxis and PPIs independently increase this risk.

Citation: O’Leary JG, Reddy KR, Wong F, et al. Long-term use of antibiotics and proton pump inhibitors predict development of infections in patients with cirrhosis. Clinical Gastro Hepatol. 2015;13(4):753-759.

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.

Clinical question: Is treatment with nontoxigenic C. diff strain M-3 (NTCD-M3) safe and effective in preventing recurrent Clostridium difficile infection (CDI)?

Background: C. diff is the most commonly identified healthcare pathogen, and CDI has a 25%-30% recurrence rate. Not all C. diff strains produce toxins, and gastrointestinal (GI) tract colonization with NTCD has been shown to prevent CDI when the patient is subsequently exposed to a toxigenic strain.

Study design: Multicenter, phase 2, randomized, double-blind, placebo-controlled, dose-ranging trial.

Setting: Forty-four centers in the U.S., Canada, and Europe.

Synopsis: Patients who had clinically recovered from CDI were randomized to placebo or NTCD-M3 at a dose of 104 spores/day for seven days, 107 spores/day for seven days, or 107 spores per day for 14 days. Patients were excluded who had multiple recurrences or other significant GI illnesses, were treated with antimicrobials other than metronidazole or PO [by mouth] vancomycin, had planned antibiotics, were unable to take PO, or had immunosuppression. Patients were monitored for side effects, rates of colonization, and incidence of CDI recurrence within six weeks.

Both overall and serious treatment-emergent adverse events were similar in patients receiving NTCD-M3 and those receiving placebo, but no statistical analysis was performed. Headache was more common in treatment groups.

CDI recurrence occurred in 31% of placebo patients and 11% of patients who received NTCD-M3 (OR 0.28). Fecal colonization was achieved in 69% of NTCD-M3 patients; this subset of patients had a 2% recurrence. Patients who received NTDC but did not achieve GI colonization had rates of recurrent CDI similar to placebo.

Bottom line: Use of NTCD-M3 spores appears safe and well tolerated and led to decreased recurrent CDI, primarily in patients who achieved fecal colonization.

Citation: Gerding DN, Meyer T, Lee C, et al. Administration of spores of nontoxigenic Clostridium difficile strain M3 for prevention of recurrent C. difficile infection: a randomized clinical trial. JAMA. 2015;313(17):1719-1727.