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ASP Scan (Weekly) for Jun 04, 2021

ASP Scan (Weekly) for Jun 04, 2021

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

US hospital data show nearly 80% of COVID-19 patients get antibiotics

Nearly 80% of US patients hospitalized for COVID-19 received antibiotics from March through October 2020, researchers from the Centers for Disease Control and Prevention (CDC) reported yesterday in Open Forum Infectious Diseases.

Using data from the Premiere Healthcare Database Special COVID-19 Release, the researchers found that 77.3% of 213,338 COVID-19 patients treated at 716 US hospitals received at least one antibiotic during their stay, and 81.3% of those who received an antibiotic were started on admission.

The antibiotic use rate in COVID-19 patients was 889 days of therapy (DOT) per 1,000 patient-days (PD), with a rate of 932 DOT/1,000 PD among patients admitted to critical care and 988 DOT/1,000 PD among those requiring invasive mechanical ventilation. The proportion of COVID-19 patients receiving antibiotics was lower during September through October (71.3%) than during March through May (80.2%).

Approximately half (49.7%) of COVID-19 patients received ceftriaxone, 44.3% received azithromycin, and 35.6% received a combination of both. Larger proportions of patients admitted to critical care or requiring invasive mechanical ventilation received vancomycin, cefepime, piperacillin-tazobactam, and meropenem.

But the data also showed that median hospital-wide antibiotic use was significantly lower during March through October 2020 compared with March through October 2019, falling from 932 to 917 DOT/1,000 PD.

“Antibiotic stewardship programs can leverage their infrastructure to address challenges that the COVID-19 pandemic has presented to healthcare professionals in the hospital setting,” the study authors wrote. “Ensuring resiliency and continuity of hospital stewardship programs is critical to optimize the treatment and outcomes of all inpatients and those with COVID-19.”
Jun 3 Open Forum Infect Dis abstract


Surveillance data indicate potentially improper treatment for candidemia

Analysis of surveillance data showed that a substantial proportion of candidemia patients initially received fluconazole, resulting in potentially inappropriate treatment of the opportunistic fungal infection, US researchers reported yesterday in Clinical Infectious Diseases.

In 2016, because of rising levels of fluconazole resistance, the increasing frequency of non-albicans Candida species (which tend to be more resistant to antifungals), and evidence that echinocandins are more effective than fluconazole, the Infectious Diseases Society of America (IDSA) changed its treatment guidelines to recommend echinocandins for initial treatment of candidemia. To assess adherence to those guidelines, researchers with the Emerging Infections Program, a collaboration between the CDC and state health departments, analyzed candidemia surveillance data from nine US sites. To identify instances of potentially inappropriate treatment, they compared the first antifungal drug received with species and antifungal susceptibility testing (AFST) results.

The analysis found that 2,415 candidemia cases occurred among 2,271 adult patients. Of these patients, 1,835 received an antifungal drug, with 68.6% receiving an echinocandin and 29.6% receiving fluconazole. Over half (56%) of the patients treated with fluconazole grew a non-albicansspecies, and among 265 patients who were treated with fluconazole and had AFST results, 10.6% had a fluconazole-resistant isolate.

Multivariable logistic regression modeling found that cirrhosis, recent hospitalization, and surveillance site were the only factors significantly associated with receipt of an echinocandin versus fluconazole, with cirrhosis patients more than twice as likely to receive an echinocandin (adjusted odds ratio, 2.06; 95% confidence interval, 1.29 to 3.29). In addition, patients at certain surveillance sites had over twice the odds of receiving an echinocandin compared with other sites, suggesting that geographic location and regional practices play a stronger role in initial candidemia therapy.

“Our findings highlight opportunities for closer adherence to IDSA guidelines on antifungal drug selection and AFST utilization, as well as the need for improved candidemia diagnostic tools,” the study authors concluded. “Further research regarding how clinicians choose antifungal drugs for candidemia and barriers to use of IDSA guidelines is also needed.”
Jun 3 Clin Infect Dis abstract


Antibiotic guidelines for COVID patients linked to reduced prescribing

Originally published by CIDRAP News Jun 3

Guidelines for antibiotic initiation and discontinuation for community-acquired bacterial pneumonia (CABP) in COVID-19 patients at a Chicago hospital were associated with reduced antibiotic prescribing and DOT, researchers reported yesterday in BMC Infectious Diseases.

Researchers at University of Chicago Medicine evaluated the duration of antibiotic therapy from Mar 1 to Apr 25, 2020, in COVID-19 patients who received at least one antibiotic for CABP before and after the Mar 28 implementation of the guidelines, which were developed by the hospital’s antimicrobial stewardship program in conjunction with infectious diseases providers. Indications to initiate empiric antibiotics included the presence of leukocytosis, fever, or chest imaging suggestive of a bacterial infections. The researchers also assessed the rate of patients receiving empiric antibiotics, hospital length-0f-stay, 30-day readmissions, and in-hospital mortality.

The retrospective study involved 506 patients, with 102 in the pre-intervention period and 404 in the post-intervention period. Prior to the guidelines, 74.5% of patients with COVID-19 received antibiotics, compared with 42% after implementation of the guidelines. The median DOT in the post-intervention group was 1.3 days shorter than the pre-intervention group, and the DOT of antibiotics directed at atypical bacteria was reduced by 2.8 days. In addition, more patients in the post-intervention group were initiated on empiric antibiotics based on criteria consistent with the guidelines (68% vs 87%). No differences in clinical outcomes were observed between the two groups.

“To our knowledge, this is the first report of an antimicrobial stewardship intervention to reduce the prescribing of empiric antibiotics for CABP in COVID-19 patients,” the study authors wrote. “Reductions in antibiotic use have important implications and can potentially reduce antimicrobial resistance and antibiotic-related toxicities.”

The authors add that further studies are needed to examine the potential clinical impact of stewardship interventions targeting antibiotic prescribing for CABP in COVID-19 patients.
Jun 2 BMC Infect Dis study


UK government to invest in antibiotic development, improved access

Originally published by CIDRAP News Jun 3

The British government today announced a £1 million ($1.4 million USD) investment to help the Global Antibiotic Research and Development Partnership’s (GARDP’s) efforts to develop and expand access to treatments for drug-resistant infections.

The money from the Global Antimicrobial Resistance Innovation Fund, part of the UK Department of Health and Social Care (DHSC), will support GARDP’s pipeline of new antibiotics and contribute to the development of SECURE, a new antibiotics initiative from GARDP and the World Health Organization. SECURE’s mission is to expand global access to new antibiotics that treat drug-resistant infections and to existing antibiotics that are not widely available or suffer from supply-chain disruptions or shortages.

“We are extremely pleased by the UK’s increased contribution at a time when COVID-19 has demonstrated the critical importance of preventing and preparing for pandemics, including the pandemic of drug-resistant infections,” GARDP Director of Research and Development Seamus O’Brien, PhD, said in a DHSC press release. “By investing an additional £1 million, the UK is again demonstrating leadership in efforts to accelerate the development and delivery of life-changing and life-saving treatments for every person who needs them.”

The UK government to date has committed £13 million to GARDP.
Jun 3 DHSC press release


Study identifies metrics tied to respiratory infection antibiotic overuse

Originally published by CIDRAP News Jun 2

More than two thirds of antibiotics prescribed for respiratory tract infections at primary care practices within an academic health system were inappropriate, with unnecessary prescribing strongly linked to respiratory infections that almost never require antibiotics, researchers reported today in Infection Control & Hospital Epidemiology.

The retrospective study by researchers with the University of Pennsylvania and the CDC looked at antibiotic prescribing for respiratory tract diagnoses (RTDs) at 32 primary care practices within the University of Pennsylvania Health in 2016. The researchers reviewed the medical records for 1,200 randomly selected office visits in which an antibiotic was prescribed for an RTD, then evaluated RTD metrics to determine their association with appropriateness. They also looked at provider characteristics associated with inappropriate prescribing.

Overall, 69% of all antibiotic prescriptions for RTDs were determined to be inappropriate, with a range of 15% to 100% for individual providers. In univariate analysis, the individual RTD metric that was most strongly associated with inappropriate prescribing was the proportion of prescribing for visits in which a tier 3 RTD was coded. Tier 3 RTDs represents conditions for which antibiotics are almost never indicated, like bronchitis. There was also a strong association between inappropriate prescribing and the proportion of prescribing for all RTDs.

Provider characteristics associated with inappropriate prescribing included advanced practice provider versus physician (72% vs 58%), family medicine providers compared with internal medicine providers (76% vs 63%), board certification in 1997 or later compared with board certification before 1997 (75% vs 63%), nonteaching versus teaching practice (73% vs 51%), and nonurban compared with urban practice (77% vs 57%).

The study authors say identifying RTD metrics associated with inappropriate prescribing can help healthcare systems track and monitor antibiotic use and highlight provider prescribing patterns.

“These findings could inform design of interventions to improve prescribing and could represent an efficient way to track inappropriate prescribing,” they wrote.
Jun 2 Infect Control Hosp Epidemiol abstract


FDA approves antifungal for vaginal yeast infections

Originally published by CIDRAP News Jun 2

Biotechnology company Scynexis announced today that the Food and Drug Administration (FDA) has approved the novel antifungal ibrexafungerp for treatment of vulvovaginal candidiasis (vaginal yeast infection).

Ibrexafungerp, sold under the brand name Brexafemme, represents the first approved drug in a novel antifungal class in more than 20 years. The first representative of a class of structurally distinct glucan synthase inhibitors known as triterpenoids, it has been granted Qualified Infectious Disease Product (QIDP) and Fast Track designations by the FDA for treatment of a variety of fungal infections caused by the Candida and Aspergillus species, including drug-resistant strains, but this is the first approved indication. The New Drug Application (NDA) was approved yesterday by the FDA.

The approval was based on the results from two phase 3 studies in which oral ibrexafungerp demonstrated efficacy and a favorable tolerability profile in women with vulvovaginal candidiasis.

“The FDA approval of Brexafemme is the culmination of years of work and a significant milestone for Scynexis, marking our evolution to a commercial-stage antifungal company. We are pleased with the approved label, highlighting the unique attributes of Brexafemme, and thrilled to be able to offer a new treatment option to women with vaginal yeast infections,” Scynexis President and CEO Marco Taglietti, MD, said in a company press release.

Scynexis says it’s completing a study of ibrexafungerp for the prevention of recurrent vaginal yeast infections, and will be submitting a supplemental NDA in 2022. Studies evaluating the efficacy in patients with invasive Candida auris infections are ongoing.
Jun 2 Scynexis press release

CARB-X funds novel antibiotics for multidrug-resistant pathogens

Originally published by CIDRAP News Jun 1

CARB-X announced today that it is awarding Swiss pharmaceutical company BioVersys up to $4.35 million to develop a new class of antibiotics to treat life-threatening infections caused by multidrug-resistant bacteria.

The award from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) will help BioVersys develop BV300, a novel class of small molecules called pyrrolocytosines that target the ribosome, which is an unexploited binding site in bacterial pathogens. The molecules have demonstrated coverage of both gram-negative and gram-positive bacteria in preclinical testing, including the ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).

Multidrug-resistant ESKAPE pathogens are common causes of severe and life-threatening infections, particularly in immune-compromised patients, patients on ventilators, and infants and young children in low- and middle-income countries (LMICs).

“Novel classes of broad-spectrum antibiotics with demonstrated in vitro and in vivo activity against all ESKAPE clinical isolates are like rare gems,” BioVersys Chief Scientific Officer Sergio Lociuro, PhD, said in a CARB-X press release. “We are excited to tackle the challenges of developing this totally new chemical class, potentially providing the first truly broadly active new class of antibiotics since decades.”

BioVersys acquired the molecules from Melinta Therapeutics, which filed for bankruptcy in 2019. The company could be eligible for an additional $10.98 million if the project achieves certain milestones.

The CARB-X portfolio currently has 61 active projects focused exclusively on drug-resistant bacteria. 
Jun 1 CARB-X press release


Surveys show rising antibiotic use in sick children in LMICs

Originally published by CIDRAP News Jun 1

Surveys from LMICs found an increase in antibiotic use in sick children under 5, with increases mainly driven by gains among groups often underserved by formal health services, according to a study last week in the International Journal of Infectious Diseases.

Researchers from Uppsala University and the University of Gothenburg in Sweden analyzed 132 Demographic and Health Surveys and Multiple Indicator Cluster Surveys conducted from 2005 through 2017 in 73 LMICs to better understand the access-excess divide in antibiotic consumption within countries. The primary outcome was the proportion of children under 5 with reported symptoms of fever, diarrhea, or cough with fast or difficult breathing who received antibiotics in the 2 weeks preceding the surveys. Reported antibiotic use was broken down by user characteristics, including rural/urban residence, maternal education, household wealth, and healthcare source visited.

Across all 73 LMICs, modelled estimates showed the greatest relative increases in rural areas, the poorest wealth quintiles, and populations with the lowest maternal education levels. In low-income countries in particular, rural areas had a greater relative increase compared with urban areas (72% vs 29%), as did the poorest wealth quintiles versus the wealthiest (67% vs 24%) and children of mothers with the lowest education levels in comparison with children of mothers with the highest education levels (72% vs 40%). Relative gains in reported antibiotic use in poor and rural children and those with mothers with low education levels were greater in Southeast Asian countries than in African countries.

Despite these observed increases, reported antibiotic use in sick children under 5 in each year of the study period was consistently highest in urban areas, the wealthiest quintiles, and populations with the highest maternal education.

The study authors say economic growth and declining poverty in many LMICs, along with increased availability of antibiotics in underserved settings, could explain the findings. They add that further research is needed to determine the appropriateness of this increased antibiotic use in sick children.
May 28 Int J Infect Dis study

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