Shiloh
Editor, Senior Moderator
Source: https://www.cidrap.umn.edu/news-perspective/2020/09/stewardship-resistance-scan-sep-16-2020
Stewardship / Resistance Scan for Sep 16, 2020
C diff vaccine candidate fails phase 3; Prior patient cultures for better antibiotics Rx
Filed Under:
Antimicrobial Stewardship; Clostridium difficile
Vaccine candidate fails to reduce C difficile infection in phase 3 trial
A phase 3 trial for a bivalent Clostridioides difficile toxoid vaccine was terminated because of futility, an international team of investigators led by scientists from Sanofi Pasteur reported yesterday in The Lancet Infectious Diseases.
In the observer-blind, randomized controlled trial, which was conducted in 326 hospitals in the United States, Canada, Latin America, Europe, and the Asia-Pacific region, adults 50 years or older with increased risk of C difficile infection were randomized 2:1 to receive one dose of Sanofi Pasteur's C difficile vaccine candidate (containing toxoids A and B) or one dose of placebo. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection.
From Jul 30, 2013, through Nov 17, 2017, 9,302 participants were enrolled, with 6,201 in the C difficile vaccine group and 3,101 in the placebo group. The first planned interim analysis reported 34 C difficile infections over 11,697.2 person-years at risk (0.29 infections per 100 person years) in the vaccine group compared with 16 C difficile infections over 5,789.4 person-years at risk (0.28 infections per 100 person-years) in the placebo group, indicating a vaccine effectiveness of –5.2% (95% confidence interval [CI], –104.1% to 43.5%). Because of those results, futility was concluded and the trial was terminated
The safety analysis found that 2,847 of 6,113 participants (46.6%) in the vaccine group reported an adverse event within 30 days of injection, compared with 1,282 of 3,057 (41.9%) in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4.8% in both groups.
The investigators suggest several factors may have played a role in the vaccine not being effective, despite showing good immunogenicity. Among the explanations are that vaccination did not generate appropriate antibody function to effectively neutralize toxin in the intestinal environment. An aging or frail immune system and previous exposure to C difficile could also be factors, they said.
"In conclusion, although the candidate vaccine was immunogenic, it failed to reduce the incidence of symptomatic C difficile infection in participants at risk," they wrote. "The findings from this trial highlight the important challenges associated with the development of vaccines against bacterial nosocomial infections, and they will inform future vaccine development."
The trial was funded and designed by Sanofi Pasteur.
Sep 15 Lancet Infect Dis abstract
Study finds use of prior patient cultures linked to better empiric antibiotics
An intervention that alerted prescribers when antibiotic prescriptions were discordant with a patient's previous culture results was associated with improved empiric antibiotic prescribing at a tertiary care academic hospital, Canadian researchers reported yesterday in Clinical Infectious Diseases.
The intervention at Sunnybrook Health Sciences Centre in Toronto was a prospective audit-and-feedback intervention in which pharmacists provided early suggestions to prescribers when a patient's initial empiric antibiotic therapy was discordant with their most recent methicillin-resistant Staphylococcus aureus (MRSA) swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and most recent culture for a gram-negative (GN) organism. The researchers analyzed the impact of the intervention using a quasi-experimental design comparing 9-month period before and after implementation.
Clinically significant discordance was identified 99 times in the pre-intervention period and 86 times in the intervention period. The proportion of patients who received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = 0.01). The proportion increased in the MRSA subgroup from 86% to 93% (P = 0.39), in the prior GN subgroup from 50% to 83% (P = 0.069), and in the ESBL subgroup from 43% to 77% (P = 0.16) for the control and intervention groups, respectively.
The median time to concordant therapy was shorter in the intervention group (25 hours vs 55 hours; P < 0.001).
The authors of the study suggest the intervention should be further evaluated in large randomized clinical trials to determine if the changes in empiric prescribing affect clinical outcomes.
Sep 15 Clin Infect Dis abstract
Stewardship / Resistance Scan for Sep 16, 2020
C diff vaccine candidate fails phase 3; Prior patient cultures for better antibiotics Rx
Filed Under:
Antimicrobial Stewardship; Clostridium difficile
Vaccine candidate fails to reduce C difficile infection in phase 3 trial
A phase 3 trial for a bivalent Clostridioides difficile toxoid vaccine was terminated because of futility, an international team of investigators led by scientists from Sanofi Pasteur reported yesterday in The Lancet Infectious Diseases.
In the observer-blind, randomized controlled trial, which was conducted in 326 hospitals in the United States, Canada, Latin America, Europe, and the Asia-Pacific region, adults 50 years or older with increased risk of C difficile infection were randomized 2:1 to receive one dose of Sanofi Pasteur's C difficile vaccine candidate (containing toxoids A and B) or one dose of placebo. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection.
From Jul 30, 2013, through Nov 17, 2017, 9,302 participants were enrolled, with 6,201 in the C difficile vaccine group and 3,101 in the placebo group. The first planned interim analysis reported 34 C difficile infections over 11,697.2 person-years at risk (0.29 infections per 100 person years) in the vaccine group compared with 16 C difficile infections over 5,789.4 person-years at risk (0.28 infections per 100 person-years) in the placebo group, indicating a vaccine effectiveness of –5.2% (95% confidence interval [CI], –104.1% to 43.5%). Because of those results, futility was concluded and the trial was terminated
The safety analysis found that 2,847 of 6,113 participants (46.6%) in the vaccine group reported an adverse event within 30 days of injection, compared with 1,282 of 3,057 (41.9%) in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4.8% in both groups.
The investigators suggest several factors may have played a role in the vaccine not being effective, despite showing good immunogenicity. Among the explanations are that vaccination did not generate appropriate antibody function to effectively neutralize toxin in the intestinal environment. An aging or frail immune system and previous exposure to C difficile could also be factors, they said.
"In conclusion, although the candidate vaccine was immunogenic, it failed to reduce the incidence of symptomatic C difficile infection in participants at risk," they wrote. "The findings from this trial highlight the important challenges associated with the development of vaccines against bacterial nosocomial infections, and they will inform future vaccine development."
The trial was funded and designed by Sanofi Pasteur.
Sep 15 Lancet Infect Dis abstract
Study finds use of prior patient cultures linked to better empiric antibiotics
An intervention that alerted prescribers when antibiotic prescriptions were discordant with a patient's previous culture results was associated with improved empiric antibiotic prescribing at a tertiary care academic hospital, Canadian researchers reported yesterday in Clinical Infectious Diseases.
The intervention at Sunnybrook Health Sciences Centre in Toronto was a prospective audit-and-feedback intervention in which pharmacists provided early suggestions to prescribers when a patient's initial empiric antibiotic therapy was discordant with their most recent methicillin-resistant Staphylococcus aureus (MRSA) swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and most recent culture for a gram-negative (GN) organism. The researchers analyzed the impact of the intervention using a quasi-experimental design comparing 9-month period before and after implementation.
Clinically significant discordance was identified 99 times in the pre-intervention period and 86 times in the intervention period. The proportion of patients who received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = 0.01). The proportion increased in the MRSA subgroup from 86% to 93% (P = 0.39), in the prior GN subgroup from 50% to 83% (P = 0.069), and in the ESBL subgroup from 43% to 77% (P = 0.16) for the control and intervention groups, respectively.
The median time to concordant therapy was shorter in the intervention group (25 hours vs 55 hours; P < 0.001).
The authors of the study suggest the intervention should be further evaluated in large randomized clinical trials to determine if the changes in empiric prescribing affect clinical outcomes.
Sep 15 Clin Infect Dis abstract