Microbiome drug for recurrent C difficile shows durable response
A secondary analysis of results from a phase 3 trial shows that an investigative microbiome therapeutic reduced rates of recurrent Clostridioides difficile infection (rCDI) through 24 weeks and was well-tolerated, researchers reported this week in JAMA.
For the analysis, researchers assessed data on rCDI rates and treatment-emergent adverse events through 24 weeks from ECOSPOR III, a double-blind multicenter trial conducted from July 2017 to September 2020. The trial randomized adults with rCDI to receive four daily capsules of SER-109—a therapeutic composed of purified Firmicutes bacterial spores developed by Seres Therapeutics—or a placebo for 3 days. Earlier published results showed SER-109 was superior to placebo through 8 weeks for treatment of rCDI (defined as three or more episodes within 12 months).
Among the 182 randomized patients, 63 had rCDI through 24 weeks, with a significantly lower proportion in the SER-109 group (19 [21.3%] vs 44 [47.3%] placebo patients). Benefit from SER-109 was evident at week 2.
Treatment-emergent adverse events (including abdominal distension, constipation, and diarrhea) occurred in 5% of patients, and more frequently in the SER-109 group than the placebo group. Serious adverse events occurred in 15 patients in the SER-109 group and 19 in the placebo group, but none were considered drug-related. Adverse events were reported in 7 patients (4 in the SER-109 group and 3 in the placebo group).
"These data support a potential role for this investigational oral microbiome therapeutic in the treatment of patients with this debilitating infection," the authors wrote.
Oct 19 JAMA research letter
More stewardship needed for postoperative antibiotics in kids, study finds
Originally published by CIDRAP News Oct 20
A multicenter observational study found that the use of antibiotics after nonemergent surgery in children varied widely across US hospitals but was not correlated with skin site infection (SSI) in children, US researchers reported yesterday in JAMA Surgery.
Using clinical outcomes and antibiotic use data from 93 hospitals participating in the American College of Surgeon's Pediatric National Surgical Quality Improvement Program, a team led by researchers with Boston Children's Hospital evaluated postoperative surgical antimicrobial use and association with SSI in children ages 18 and under who underwent nonemergent clean and clean-contaminated procedures from June 2019 through June 2021.
Use of postoperative prophylaxis was defined as continuation after incision closure of one or more of the same antibiotics used before and during the procedure—a practice common in pediatric surgery but not recommended by guidelines because of evidence demonstrating a lack of benefit. The primary outcome was 30-day postoperative SSI rate.
A total of 40,611 patients were included in the analysis, of which 41.6% received postoperative prophylaxis (hospital range 0% to 71.2%). Odds ratios (ORs) for postoperative prophylaxis use ranged 190-fold across hospitals (OR, 0.10 to 19.30), and ORs for SSI rates ranged 4-fold (OR, 0.55 to 1.90).
But no correlation was found between use of postoperative prophylaxis and SSI rates overall (Pearson correlation coefficient [r] = 0.13; P = .20), nor when stratified by SSI type (incisional SSI, r = 0.08; P = .43 and organ space SSI, r = 0.13; P = .23), and surgical specialty (general surgery, r = 0.02; P = .83; urology, r = 0.05; P = .64; plastic surgery, r = 0.11; P = .35; otolaryngology, r = −0.13; P = .25; orthopedic surgery, r = 0.05; P = .61; and neurosurgery, r = 0.02; P = .85).
The study authors say the findings indicate that implementing targeted stewardship efforts to reduce postoperative antibiotic use in pediatric surgery is possible without an increase in the SSI rate.
"The results of this analysis provide a call to arms for stewardship efforts to reduce postoperative prophylaxis use, particularly for hospitals that are relatively high users compared with their peers," they wrote.
Oct 19 JAMA Surg abstract
Small trial supports shorter antibiotics for kids' pneumonia
Originally published by CIDRAP News Oct 20
A randomized clinical trial conducted in Canada found that 5 days of high-dose amoxicillin was non-inferior to 10 days in children with community-acquired pneumonia (CAP), researchers reported this week in the Journal of the Pediatric Infectious Diseases Society.
The blinded, noninferiority trial enrolled children ages 6 months to 10 years who were treated as outpatients for CAP at two pediatric emergency departments in Canada. Trial participants were randomized 1:1 to receive either 5 days of high-dose amoxicillin followed by 5 days of a placebo or an additional 5 days of amoxicillin.
The primary outcome was clinical cure defined as improvement within 4 days of enrollment, improvement in the work of breathing and no tachypnea at follow-up (14 to 21 days), no more than one fever after day 4, and no additional antibacterial therapy or hospital admission because of lower respiratory tract illness.
A total of 254 children were randomized, with 126 in each arm. In the intention-to-treat analysis, clinical cure at 14 to 21 days occurred in 85.7% of children in the 5-day amoxicillin group and 84.1% in the 10-day amoxicillin group. In a secondary (post hoc) analysis that defined clinical cure as initial improvement during the first 4 days and lack of need for additional antibacterial therapy or hospital admission, about 93.5% in the 5-day group and 90.4% in the 10-day group met these criteria.
The study authors note that the trial did not definitively identify patients as having bacterial pneumonia, and of the children who had a baseline respiratory panel, more than 60% had a virus identified, which may have affected the trial's ability to detect a difference between short- and standard-course antibiotics. Nonetheless, they say the findings still add to the growing body of evidence that short-course antibiotic therapy is effective for CAP.
They conclude, "In the face of increasing antimicrobial resistance and accumulating evidence of the harms of antibiotics, clinicians should consider a 5-day course of high-dose amoxicillin for CAP in children who do not require hospitalization. As pediatric CAP guidelines are updated, these data should inform new recommendations for the duration of treatment of outpatients with CAP."
Oct 19 J Ped Infect Dis Soc abstract
Study finds extensive antibiotic use on poultry farms in Bangladesh
Originally published by CIDRAP News Oct 19
A cross-sectional survey revealed extensive antibiotic use in commercial chicken production in Bangladesh, researchers reported this week in PLOS One.
To assess antibiotic use on chicken farms in Bangladesh, where commercial chicken production has been expanding to meet rising demand, an international team of researchers surveyed chicken farms across the country. They collected data on demographics, poultry species, antibiotic use preceding the interview, and type of antibiotics used. They also measured the association between antibiotic use and factors related to the characteristics of the farms and farmers.
Among the 768 farms surveyed, 41% reported using antibiotics within the previous 24 hours, 45% reported antibiotic use within the previous 72 hours, and 86% reported antibiotic use within the previous 2 weeks. In all timeframes, antibiotic use was more common among broiler and Sonali (a crossbreed chicken) farms than layer farms. Almost all farms (98%) had used antibiotics since the start of their production cycle. Oxytetracycline, doxycycline, ciprofloxacin, and amoxicillin were the most frequently used antibiotics.
Antibiotics were reported to be used for both treatment and prophylactic (disease prevention) purposes on most farms (57% to 67%), with many farmers saying they used antibiotics for fattening purposes. Antibiotic usage was mainly advised by veterinary practitioners (45% to 71%, depending on production type), followed by feed dealers (21% to 40%) and farmers (7% to 13%).
Multivariable analysis indicated that the use of antibiotics in the 24 hours preceding an interview was significantly associated with the occurrence of any illnesses in broilers (adjusted odds ratio [aOR], 41.22 ; 95% confidence interval [CI], 13.63 to 124.62), layers (aOR, 36.45; 95% CI, 9.52 to 139.43), and Sonali chickens (aOR, 28.47; 95% CI, 4.97 to 162.97).
"The findings from this study emphasize that the improvement of chicken health through good farming practices can help to reduce antibiotic use and the consequential development of antimicrobial resistance," the study authors wrote. "Regular monitoring of antibiotic usage, educating farmers, drug sellers, and feed dealers about effective use of antibiotics, and restricting ease of access to antibiotics, may also be useful to reduce unnecessary use of antibiotics in commercial chicken production systems."
Oct 17 PLOS One study
New toolkit aims to improve ambulatory antibiotic prescribing
Originally published by CIDRAP News Oct 18
The US Agency for Healthcare Research and Quality (AHRQ) yesterday released a new toolkit to help hospitals improve antibiotic use in ambulatory care.
Centered around AHRQ's Four Moments of Antibiotic Decision Making framework, the toolkit aims to improve antibiotic prescribing in settings like doctor's offices and urgent care clinics—where most antibiotics are prescribed and where unnecessary antibiotic use is common—using online presentations, guidelines, and other educational tools. The focus is on helping ambulatory care practices develop and strengthen their antibiotic stewardship infrastructure, providing strategies for communicating with patients about antibiotic prescribing, and teaching best practices for diagnosing and managing common infectious syndromes.
The toolkit is based on an AHRQ Safety Program rolled out at primary care, urgent care, pediatric care, and other US ambulatory clinics in December 2019.
In a paper published in JAMA Network Open in July, researchers found that the program was associated with a 9% absolute decrease in antibiotic prescribing from December 2019 through November 20202 in 389 clinics that participated in the program. The study also found that participating clinics showed improvements in the infrastructure needed to maintain antibiotic stewardship programs.
Oct 18 AHRQ ambulatory care toolkit
Jul 12 CIDRAP News story
GARDP receives additional funding from Germany
Originally published by CIDRAP News Oct 18
The German government announced yesterday that it will provide €50 million ($49.15 million US) in funding over 5 years to the Global Antibiotic Research and Development Partnership (GARDP) to develop treatments for drug-resistant infections.
The money from the German Federal Ministry of Education and Research, which was announced at the World Health Summit in Berlin, brings the total German contribution to GARDP to €116 million since 2016.
"We are deeply grateful to Germany for its renewed investment in GARDP, which characterizes their remarkable leadership in global health and efforts to tackle the existing pandemic of antibiotic resistance," GARDP Executive Director Manica Balasegaram, MRCP, MSc, said in a press release. "Germany's contribution recognizes that effective antibiotics are the foundation of modern medicine. Without them, routine surgery, childbirth, and chemotherapy will no longer be safe, and common infections will no longer be treatable."
GARDP has also received recent funding from the governments of Monaco and Canada to address neonatal sepsis in Africa and further develop an initiative to provide antibiotic access to countries in need.
Oct 17 GARDP press release
Study: Antimicrobial resistance rates rose in US hospitals during COVID-19
Originally published by CIDRAP News Oct 17
A new analysis of data on US hospital patients during the COVID-19 pandemic finds that patients tested for SARS-CoV-2 had a higher rate of antimicrobial resistance (AMR), researchers reported today in Open Forum Infectious Diseases.
To evaluate changes in AMR rates among hospital patients before and during the pandemic, researchers with Merck and Becton, Dickinson and Company analyzed record on adults hospitalized for at least 1 day at 271 US hospitals from July 2019 through October 2021.
All admissions with an AMR event, defined as a non-contaminated first positive culture for gram-negative or gram-positive pathogens of interest with reported non-susceptibility, were included in the analysis. The researchers evaluated overall AMR rates, comparing the pre-pandemic period (July 2019 through February 2020) with the pandemic period (March 2020 through October 2021).
Of the more than 5.5 million admissions evaluated, AMR events were detected in 35.4 per 1,000 admissions during the pre-pandemic period and 34.7/1,000 admissions during the pandemic period. Patients tested for SARS-CoV-2 had a significantly higher AMR rate than that observed in the pre-pandemic period (49.2/1,000 admissions for patients who tested positive, 41.1/1,000 admissions for negative patients, and 25.7/1,000 admissions for untested patients).
AMR rates among community-onset (CO) infections during the pandemic were lower compared with pre-pandemic levels (26.1/1,000 admissions vs 27.6/1,000), while AMR rates for hospital-onset (HO) infections were higher (8.6/1,000 admissions vs 7.7/1,000), driven largely by SARS-CoV-2–positive admissions (21.8/1,000 admissions). Multivariable analysis found that rates of AMR were associated with overall antibiotic use, rates of positive cultures, longer hospital stays, and higher use of inadequate empiric antibiotic therapy.
"While our data suggest no significant change in overall AMR rates during the pandemic compared to pre-pandemic periods, higher rates of AMR in SARS-CoV-2–positive HO infections have been observed," the study authors wrote. "To mitigate the potential-long-term impact of COVID-19 on AMR, it is critical to continue to monitor AMR rates in later stages of the pandemic, effective antimicrobial use, as well as strategies to control modifiable factors contributing to AMR, particularly in SARS-CoV-2–positive patients with HO infections."
Oct 17 Open Forum Infect Dis abstract
New One Health plan aims to address AMR, other epidemics
Originally published by CIDRAP News Oct 17
Four international organizations today released a new One Health Joint Plan of Action that includes a framework for collaboration on AMR.
The framework outlined by the Quadripartite Organizations—the World Health Organization (WHO), the World Organization for Animal Health, the United Nations Environment Programme, and the Food and Agriculture Organization of the United Nations—calls for the organizations to do more to support AMR control at the country level.
Among the deliverables listed in the plan are helping low- and middle-income countries (LMICs) implement One Health-based AMR National Action Plans and providing technical support and guidance to help LMICs build integrated AMR and antibiotic use surveillance systems and develop AMR awareness campaigns.
The framework also calls on the organizations to coordinate the global One Health response to AMR, provide political advocacy, strengthen regional collaboration and global AMR governance structures, develop a prioritized research agenda, and conduct monitoring and evaluation of country-level efforts.
The One Health concept views the health of humans, animals, and the environment as intrinsically linked. Addressing AMR is one of six "action tracks" listed in the plan, which aims to improve the world's ability to prevent, predict, detect, and respond to health threats against humans, animals, plants, food, and the environment.
"Because AMR has multiple drivers and needs to be tackled on many fronts, a One Health approach is essential to ensure that all sectors and stakeholders communicate and work effectively together," the plan states.
Other action tracks include strengthening health systems, reducing risks from zoonotic epidemics and pandemics, controlling and eliminating vector-borne diseases, and strengthening assessment, management, and communication of food safety risks.
"It's clear that a One Health approach must be central to our shared work to strengthen the world's defences against epidemics and pandemics such as COVID-19. That's why One Health is one of the guiding principles of the new international agreement for pandemic prevention, preparedness and response, which our Member States are now negotiating," WHO Director-General Tedros Adhanom Ghebreyesus, PhD, said in a press release.
Oct 17 One Health Joint Plan of Action
Oct 17 WHO press release