Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans
Early national study results indicate FMT safe, effective for C diff
Initial results from the FMT (fecal microbiota transplantation) National Registry indicate that FMT is highly effective for treating Clostridioides difficile infection (CDI), with a good safety profile, US researchers reported yesterday in Gastroenterology.
The FMT National Registry is an ongoing, prospective, observational, multicenter registry of North American patients who receive FMT for any indication, designed to assess FMT methods of delivery, as well as the safety and effectiveness of the procedure. Data are collected by participating sites at baseline and at 1 month, 6 months, 1 year, and 2 years after the procedure. The primary outcome analyzed in this study was cure of CDI at 1 month. Safety outcomes included patient symptoms, infections, hospitalizations, deaths, and changes in current medical conditions or development of new conditions.
Of the first 259 participants enrolled at 20 sites, 222 completed follow-up at 1 month, and 123 had follow-up at 6 months. All procedures were performed for CDI, and 249 (96%) used stool from an unknown donor, primarily a stool bank. The primary method of delivery was colonoscopy (221 patients, 85%). Of the 222 patients with 1-month follow-up, 200 (90%) had CDI cure, with 197 (98%) requiring only one treatment to achieve cure. Among 112 with initial cure who were followed to 6 months, 4 (4%) had CDI recurrence.
Severe symptoms reported within 1 month of FMT included diarrhea (2 patients, 5%), abdominal pain (4 patients, 2%). Hospitalizations were reported in 27 patients (12%), but only 3 hospitalizations (1%) were possibly related to FMT. At 6 months, new diagnoses of irritable bowel syndrome were made in 2 patients (1%) and inflammatory bowel disease in 2 patients (1%).
"CDI cure rates were excellent at approximately 90% and in line with those reported in RCTs [randomized controlled trials] of FMT and in a National Pediatric FMT Registry," the authors of the study wrote. "Thus, patients can expect to achieve high rates of success with FMT for refractory CDI in standard clinical practice."
The authors say assessment of new conditions at long-term follow-up is planned as the registry grows and will be important for determining the full safety profile of FMT.
Oct 2 Gastroenterology abstract
Dutch group recommends restrictive antibiotic use in COVID patients
Originally published by CIDRAP News Oct 1
Based on available evidence and antibiotic stewardship principles, a committee of Dutch clinicians and researchers is recommending restrictive use of antibiotics in COVID-19 patients, according to guidelines published yesterday in Clinical Microbiology and Infection.
With the intention of developing evidence-based recommendations for the use of antibiotics in patients with a respiratory infection and suspected or confirmed COVID-19, the Dutch Working Party on Antibiotic Policy conducted a review and analysis of literature on COVID-19 and bacterial co-infections and secondary infections.
They set out to answer four key questions about the risk of bacterial pneumonia in patients with suspected or confirmed COVID-19, the causative bacterial species, the optimal approach to diagnosing or refuting bacterial pneumonia, and the optimal antibiotic choice.
The committee found that bacterial co-infection upon admission occurred in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred in up to 15% of patients. But not enough evidence was available to answer the other questions.
The committee agreed that clinicians should always assess the risk of a bacterial infection in patients with suspected COVID-19 and that antibiotic therapy should be considered if the clinician has a high suspicion of bacterial co-infection in a patient with radiologic findings and/or inflammatory markers compatible with bacterial co-infection.
But they also said maximum efforts should be undertaken to obtain sputum and blood culture samples and conduct pneumococcal urinary antigen testing and suggested that antibiotics be stopped if results show no signs of bacterial pathogens after 48 hours.
The committee recommended an antibiotic treatment duration of 5 days in patients with COVID-19 and suspected bacterial respiratory infection, contingent upon improvement in signs, symptoms, and inflammatory markers.
The committee says larger, prospective studies on the epidemiology of bacterial co-infections and secondary infections in COVID-19 patients are needed to confirm their conclusions.
Sep 30 Clin Microbiol Infect study
Study: California ASP mandate associated with C diff reduction, MRSA rise
Originally published by CIDRAP News Oct 1
A study today in Infection Control & Hospital Epidemiology shows that California's antimicrobial stewardship program (ASP) mandate was associated with a decrease in C difficile infection (CDI) rates and an increase in methicillin-resistant Staphylococcus aureus (MRSA) rates in acute care hospitals.
To evaluate the impact of a 2014 law that required acute care hospitals in California to adopt and implement an ASP, researchers analyzed hospital-level data covering 2013 through 2017 from the Centers for Medicare and Medicaid (CMS) Hospital Compare, Provider of Service, and Medicare Cost Reports files. They then compared the MRSA and CDI standardized infection ratio (SIR) for California acute care hospitals with those in other states.
In 2013, the average SIR in California hospitals was 0.79 for MRSA, compared with 0.94 for hospitals in other states, and the average CDI SIR was 1.01, versus 0.77 for other states. In 2015, 2016, and 2017, California hospitals had 23%, 30%, and 20% increases in MRSA SIRs compared with other states, while the CDI SIR decreased by 20%, but only in 2017.
Although the decrease in CDI SIR was expected because the ASP mandate restricted antibiotic use in California hospitals, the authors of the study say the increase in MRSA SIR may be the result of more proactive identification of antibiotic-resistant pathogens. They also note that the impact of ASPs is likely stronger for gram-negative microorganisms because most of the restricted antibiotics are for gram-negative infections (MRSA is gram-positive).
The authors add that more data on postintervention years are needed to assess the long-term impact of the California mandate and that ASP mandates in other states should be studied.
Oct 1 Infect Control Hosp Epidemiol abstract
Analysis: AMR Action Fund won't fix broken antibiotic market
Originally published by CIDRAP News Oct 1
A pharmaceutical industry effort to fund development of new antibiotics through investment in small companies could buy time for reforms to address the underlying market problems facing antibiotic development but will not fix those problems on its own, according to a new analysis in Open Forum Infectious Diseases.
The AMR Action Fund, launched in June by 20 of the world's largest pharmaceutical companies, aims to invest $1 billion in small antibiotic companies with promising products, with the goal of bringing two to four new antibiotics to market by 2030.
Although many of these large drug makers have abandoned antibiotic development because of the lack of financial return on antibiotics, the hope is that their money and technical assistance can help the smaller companies, which struggle financially, bring innovative new products to market and boost the antibiotic development pipeline.
But the analysis of the AMR Action Fund by clinicians with the University of Pittsburgh Department of Medicine and the VA Pittsburgh Healthcare System suggests that while the fund will provide a financial lifeline to struggling companies, it does not address the biggest problem—the low reimbursement for new antibiotics and the need to de-link reimbursement from numbers of prescriptions.
The analysis also highlights how the fund fails to address three particular issues that have contributed to the financial failure of new antibiotics for carbapenem-resistant bacteria: slow clinical uptake by clinicians; the relatively small number of carbapenem-resistant infections that occur in the United States; and an excess of new agents that aren't superior to current antibiotics.
"The Fund's major weaknesses are that it does not directly address the 3 issues identified in our case study, nor will it fix the broken marketplace," the authors wrote. "Its most important charge will be to buy time to convince governments to enact reimbursement reforms ('pull' incentives) or implement new antibiotic development models."
Sep 30 Open Forum Infect Dis abstract
Review shows stewardship apps increase guideline accessibility
Originally published by CIDRAP News Sep 30
A review of studies analyzing use of antimicrobial stewardship (AMS) apps found they may increase adherence to antibiotic prescribing guidelines, European researchers reported yesterday in PLOS One.
The review, led by researchers from Erasmus Medical Center in the Netherlands, included 13 studies published from 2008 to 2019 focusing on the use of AMS smartphone or tablet app use by physicians treating in-hospital patients. The aim of the study was to review the apps and evaluate their impact on antibiotic prescribing for in-hospital patients. The primary study outcomes included average monthly use, guidelines assessed, adherence to guidelines, and user experience.
In general, the studies measured different outcomes, applied different designs, and varied in quality. None of them were randomized controlled trials. In four studies, guideline-adherent antibiotic prescribing increased significantly (6.5% to 74%) after app implementation, and in one study, this resulted in significantly less resistance to some antibiotics and a decrease in total drug costs.
Most users considered the apps easy to use (77.4% to >90.0%) and useful (71.0% to >90.0%) in three studies, and preferred guideline access via app to desktop or booklet in two studies. In three studies, some physicians reported that use of apps in front of patients or colleagues felt unprofessional.
The authors of the review say that while the studies indicate that apps may increase guideline accessibility, because of the small number of studies and the limited quality of the data, they can't draw any conclusions on the advantages of AMS app use in hospital settings.
"High quality, randomized, multi-centre studies including robust clearly defined clinical, microbiological and process outcomes are needed to evaluate the impact of AMS apps on antimicrobial prescribing and its role within healthcare," they wrote.
Sep 29 PLOS One study
BARDA to fund two new antibacterial drug candidates
Originally published by CIDRAP News Sep 30
The Biomedical Advanced Research and Development Authority (BARDA) today announced advanced funding for two new drug candidates that target bacterial infections.
The two drug candidates are VE303, a live biotherapeutic product developed by Vedanta Biosciences that focuses on restoring the normal balance of beneficial bacteria in the digestive tract to prevent recurrence of C difficile, a bacterial infection associated with antibiotic use. The other is Locus Biosciences' LBP-EC01, which uses CRISPR-Cas3 technology and bacteriophages to treat urinary tract infections caused by Escherichia coli, including those that are antibiotic resistant.
BARDA, part of the Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response, will provide an initial $7.36 million and up to $76.9 million over 9.5 years to Vedanta to support development of VE303 and an initial $11 million and up to $77 million to Locust for LBP-EC01. The funding will support phase 2 and phase 3 trials of the drugs.
The Centers for Disease Control and Prevention has identified C difficile and antibiotic-resistant E coli as serious and urgent health threats.
"Healthcare providers need tools at-the-ready to prevent or combat secondary bacterial infections, particularly those that impact a patient's successful recovery following antibiotic usage in a public health emergency," BARDA Acting Director Gary Disbrow, PhD, said in a press release. "Infections associated with long-term antibiotic use are a growing concern and are often costly to treat which makes developing novel drugs and technologies for prevention and treatment all the more urgent for U.S. health security."
Sep 30 HHS press release
Study highlights changing epidemiology of carbapenem-resistant bacteria
Originally published by CIDRAP News Sep 29
Highlighting trends that could be reflected on a national level, a study today in Clinical Infectious Diseases shows that rates of carbapenem-resistant gram-negative bacteria (CRGNB) increased from 2000 through 2017 at a Pittsburgh hospital, and mortality was high among patients with CRGNB infections, but clinical outcomes improved over time.
To evaluate the changing epidemiology and clinical impact of CRGNB over time, a team led by researchers at the University of Pittsburgh School of Medicine looked at data and microbiology records on all patients at the University of Pittsburgh Medical Center with a positive clinical culture from 2000 through 2017. Carbapenem resistance was defined as non-susceptibility to carbapenem based on 2017 breakpoints and applied across the study period. The researchers assessed overall carbapenem resistance rates, pathogen-specific incidence rates, rates of antibiotic consumption, and patient outcomes.
The researchers evaluated a total of 94,888 isolates from 64,222 patients over the study period and found 10.4% of those isolates were carbapenem-resistant, accounting for a total 5,450 cases from 4,038 unique patients. Overall rates of carbapenem resistance increased from 6% to 11%, and they increased significantly for each pathogen over the study period. Pseudomonas aeruginosa was the most common CRGNB each year, but the second most common CRGNB varied over time (Acinetobacter spp. from 2007-2010, Klebsiella pneumoniae from 2011-2012, and Enterobacter spp. from 2013-2014). Isolation of CRGNB was common among transplant recipients and patients with multiple comorbid conditions.
The rate of CRGNB isolation increased from 0.81 to 1.65 per 1,000 patient-days over the study period, and carbapenem defined daily doses increased from 6.5 to 35.1 per 1,000 patient-days.
Evaluation of patient outcomes showed that overall 30- and 90-day mortality among CRGNB patients was 19% and 31%, respectively, with higher rates (27% and 38%) for CRGNB bloodstream infections. But the 30-day mortality rate declined from 24% in 2000 to 17% in 2017. The median lengths of total and post-CRGNB isolation hospital stays were 26 days and 13 days, respectively.
"CRGNB emerged in waves over time causing high rates of mortality," the authors wrote. "Despite increasing rates of CRGNB, overall patient outcomes have improved, suggesting that recognition and novel therapeutics have made a major impact."
Sep 29 Clin Infect Dis abstract
FDA approves cefiderocol for hospital-acquired, ventilator-associated pneumonia
Originally published by CIDRAP News Sep 28
Japanese drug maker Shionogi, with US headquarters in Florham Park, New Jersey, announced today that the Food and Drug Administration (FDA) has approved the company's supplemental New Drug Application for cefiderocol.
The FDA's approval means that cefiderocol, sold under the brand name Fetroja, can be used to treat patients who have hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by gram-negative pathogens. The antibiotic was initially approved for treatment of complicated urinary tract infections.
The expanded indication is based on the results of a phase 3 APEKS-NP trial, which showed that cefiderocol was non-inferior to meropenem for treating HABP/VABP patients.
"Nosocomial pneumonia is one of the most common hospital-acquired infections and a rising number are caused by difficult-to-treat, multidrug-resistant pathogens, which can be a deadly threat for patients," lead trial investigator Richard Wunderink, MD, of Northwestern University's Feinberg School of Medicine, said in a company press release. "The results from the APEKS-NP study show that cefiderocol is a much-needed additional option for the treatment of patients with HABP and VABP due to multidrug-resistant gram-negative bacteria."
Cefiderocol is a cephalosporin antibiotic with a novel mechanism of penetrating the tough outer membrane of gram-negative bacteria with and the ability to overcome resistance mechanisms used by gram-negative pathogens to evade antibiotics.
Sep 28 Shionogi press release
Fecal transplant provides long-term C diff protection despite exposures
Originally published by CIDRAP News Sep 28
Mayo Clinic researchers report that FMT was 78% effective at preventing CDI recurrence at 1 year despite subsequent exposure to the toxoid in 460 FMT patients.
The retrospective study, published late last week in Clinical Infectious Diseases, found that 76.8% of adult patients were exposed to the healthcare system after FMT, and 78.1% of 374 patients with risk factor exposure had a durable response at 1 year.
The most common underlying diseases in the patients were inflammatory bowel disease (21.9%), chronic liver disease (12.8%), cancer (11.7%), and chronic kidney disease (3.9%). In total, 31.3% of patients received antibiotics for their infections, while 21.7% received acid suppressants. In multivariable analysis, use of antibiotics was independently tied to a less durable response (hazard ratio, 0.27).
The authors concluded, "Majority of patients had a durable response to FMT despite exposure to CDI risk factors." They called for larger studies to identify predictors of durable response in patients who have and have not taken antibiotics.
CDI, the leading cause of diarrhea in hospital patients is one of the most common infections associated with exposure to the healthcare system. FMT, which involves the transfer of stool from a healthy donor into the colon of an infected patient, is reserved for patients who have had several CDI bouts that didn't respond to antibiotic treatment.
Sep 25 Clin Infect Dis abstract