ASP Scan (Weekly) for May 28, 2021

News brief

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

GARDP urges nations to strengthen response to drug resistance

The Global Antibiotic Research and Development Partnership (GARDP), on behalf of the Drugs for Neglected Diseases initiative, issued a statement this week that called on World Health Organization (WHO) member states to strengthen their responses to antimicrobial resistance (AMR).

The statement, presented at the 74th annual World Health Assembly, said the consequences of the COVID-19 pandemic highlighted the need for investment and international cooperation to prepare for and address the ongoing impacts of AMR.

"Like COVID-19, drug-resistant bacteria can infect anyone, of any age, in any country," GARDP said in the statement. "Unlike COVID-19, we can prepare now. The drug-resistant microbes are known, and meaningful change can be achieved with sufficient political will and resources."

Citing a recent WHO review that concluded the antibiotic pipeline is insufficient to address AMR, GARDP called the current global response to rising drug resistance "off course" and urged immediate action. The group called on member states to invest in the development of medical countermeasures for priority infections; develop and fund mechanisms to accelerate equitable and affordable access to diagnostics, treatments, and vaccines; and expand global cooperation across geographies and sectors within a One Health framework.

GARDP also said member states should ensure that low- and middle-income countries are equal partners in a comprehensive global response.
May 26 GARDP statement

CARB-X to fund development of CRISPR-based drug for E coli infections

Originally published by CIDRAP News May 27

CARB-X announced today that it is awarding up to $3.9 million to a Danish microbiome biotechnology company to develop a CRISPR-based drug to prevent Escherichia coli infections in cancer patients.

The award will help Copenhagen-based SNIPR BIOME ApS develop its lead drug candidate, SNIPR001, which uses CRISPR/Cas DNA editing technology to selectively eradicate E coli bacteria in the gut and prevent translocation of the bacteria to the bloodstream while sparing other beneficial bacteria in the patient's microbiome.

Cancer patients with hematologic malignancies are often at increased risk of bloodstream infections because of the disease and chemotherapy treatment, with E coli posing a heightened risk. They are typically treated with broad-spectrum antibiotics.

"There is an increasing awareness of the importance for human health of microbial diseases and anti-microbial resistance," SNIPR BIOME Chief Medical Officer Milan Zdravkovic, MD, PhD, said in a CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) press release. "We see that SNIPR001 has the potential to contribute to addressing unmet medical needs in a novel way in people at high risk of severe E. coli infections, and we look forward to working with CARB-X in bringing SNIPR001 into clinical trials."

SNIPR BIOME may be eligible for an additional $6.3 million if the project achieves certain milestones. The company hopes to begin a first in-human study in the first half of 2022.

Since its launch in 2016, CARB-X has announced 90 awards to product developers in 12 countries. The awards are worth more than $337 million.
May 27 CARB-X press release

New WHO guidance aims to help nations implement stewardship steps

Originally published by CIDRAP News May 27

The WHO has published new guidance for countries on how to implement antimicrobial stewardship (AMS) activities in healthcare facilities in an integrated, comprehensive manner.

The guidance, which was requested by member states and is intended for policy makers at national ministries of health and national AMR coordinating bodies, was developed by WHO staff with input from an international group of experts, including those from the University of Minnesota's Centers for Infectious Disease Research and Policy, publisher of CIDRAP News.

The guidance is organized into five key pillars and 12 interventions that countries need to consider to implement comprehensive and integrated AMS activities in healthcare facilities. The WHO defines AMS as a coherent set of integrated actions that promote responsible and appropriate use of antimicrobials and help improve patient outcomes across the continuum of care.

The five key pillars of the guidance are: (1) Establish and develop national coordinating mechanisms for antimicrobial stewardship and develop guidelines; (2) ensure access to and regulation of antimicrobials; (3) improve awareness, education, and training; (4) strengthen water, sanitation, and hygiene and infection prevention and control (IPC); and (5) conduct surveillance, monitoring, and evaluation.

Interventions include establishing a national coordination mechanism for AMS activities that can function at national, subnational, and district levels, developing national treatment and stewardship guidelines, regulating responsible and appropriate use of antimicrobials, implementing IPC core components in health facilities, and establishing surveillance systems for antibiotic use and AMR.

"AMS activities are best implemented in an integrated manner to optimize antimicrobial prescribing and ensure patient and public safety," the guidance states. "It is important that the central coordination unit takes the lead, involving all relevant stakeholders in national policy development and strategic planning processes to identify the priority objectives, inputs and resources required and, finally, to implement the policy."

The guidance also advises that the central coordination unit should consider national and local context and the structure of the health system in carrying out AMS activities, prioritize activities that are likely to provide the greatest benefit, and ensure strong links between relevant areas and disciplines related to AMR.
May 20 WHO policy guidance

Study examines inadequate antibiotics in patients tested for COVID-19

Originally published by CIDRAP News May 27

Inadequate antibiotic therapy (IET) in hospital patients with positive bacterial cultures who were tested for SARS-CoV-2 was associated with a significant increase in mortality and longer hospital stays compared with those who received adequate therapy, US researchers reported yesterday in Open Forum Infectious Diseases.

The multicenter retrospective study, conducted by scientists with Merck & Co. and Becton, Dickinson and Company, looked at in-hospital mortality and hospital and intensive care unit (ICU) length of stay (LOS) in patients who were tested for SARS-CoV-2 and had a positive bacterial culture at 201 US hospitals from March to November 2020. While high rates of empiric antibiotic use have been reported in COVID-19 patients throughout the pandemic, little research has been conducted on the impact of IET—defined as therapy not active against the identified bacteria or no antibiotic therapy in the 48 hours following culture—on patient outcomes.

Of the 438,888 patients who were tested for COVID-19, 39,203 (8.9%) had positive bacterial cultures. Among the patients with positive cultures, 3,764 (9.4%) were SARS-CoV-2–positive, 74.4% had a gram-negative pathogen, and 25.6% had a gram-positive pathogen. Overall, 17,295 (44.1%) of these patients received IET, with the absence of empiric treatment within 48 hours more common than antibiotic therapy that was not active against the identified bacteria.

In multivariable analysis, IET was associated with a 21% increase in mortality (odds ratio, 1.21; 95% confidence interval, 1.10 to 1.33) compared with adequate antibiotic therapy, and a significant increase in hospital LOS (16.1 days vs 14.5 days). The difference in ICU LOS was not statistically significant (8.2 days vs 8.0 days). Both mortality and hospital LOS findings remained consistent for patients who tested positive for SARS-CoV-2 and those who tested negative.

"Our data indicate that underlying gram-positive and gram-negative bacteria continue to play an important role in hospital outcomes during the COVID19 pandemic, and one with the potential to be adequately managed to help ensure more favorable outcomes," the authors wrote, adding that they hope the study enables stewardship programs to educate and contain IET in hospitals for all patients with bacterial infections.
May 26 Open Forum Infect Dis abstract

More US nursing homes using antibiotic stewardship elements

Originally published by CIDRAP News May 26

An analysis of US nursing home surveys shows substantial progress in antibiotic stewardship element implementation, researchers with the Centers for Disease Control and Prevention (CDC) reported today in Infection Control & Hospital Epidemiology.

Looking at 7,506 National Healthcare Safety Network (NHSN) Long-Term Care Facility Component annual surveys conducted from 2016 through 2018, the researchers found that 1,323 nursing homes (71% of those enrolled in NHSN) reported implementing all seven of the CDC's core elements of antibiotic stewardship in 2018, a 28% increase from 2016.

Among the core elements, the greatest increases in implementation were in education of staff, residents, and families ( 19%); reporting information on antibiotic use (18%), and access to drug expertise (15%)—all of which had the lowest reported implementation in 2016. Pharmacist involvement in improving antibiotic use increased by 27% since 2016.

A multivariable analysis found that nursing homes that reported at least 20 hours of infection prevention control activity per week were 14% more likely to implement all seven core elements, when controlling for facility ownership and affiliation.

The study authors say the increase in implementation of the core elements was likely driven by antibiotic stewardship requirement imposed by the Centers for Medicare & Medicaid Services in November 2017 but may also reflect greater awareness and additional resources.

"Further research should evaluate the barriers facing nursing homes in implementing successful antibiotic stewardship policies and should identify the stewardship activities that are most feasible, sustainable, and effective in improving prescribing practices and resident outcomes in nursing home settings," they wrote.
May 26 Infect Control Hosp Epidemiol abstract

In India, 47% of bacterial infections in COVID patients multidrug-resistant

Originally published by CIDRAP News May 25

A retrospective study of COVID-19 patients in India found a low prevalence of secondary bacterial or fungal infections, but gram-negative pathogens predominated, high rates of antibiotic resistance were observed, and mortality was high, Indian researchers reported yesterday in Infection and Drug Resistance.

Of the 17,534 COVID-19 patients admitted to the intensive care units and wards of 10 Indian hospitals from June to August 2020, 640 (3.6%) patients developed secondary bacterial infections (585/640, 91.4%) or fungal infections (35/640, 5.4%), with a range of 1.7% to 28% across hospitals. Among those patients, 78% acquired the infections in the hospitals (48 hours or more after admission), and the median number of days to develop an infection varied from 3 to 15 days.

Of the pathogens isolated from blood, respiratory specimens, and urine, 78.3% were gram-negative bacteria, and Klebsiella pneumoniae (29.3%) and Acinetobacter baumannii (21.1%) were the most commonly isolated pathogens. Candida spp were isolated from 6% of patients with secondary fungal infections, with 13 Candida auris (1.3%) isolates found.

Among the patients with secondary infections, 47.1% were infected with multidrug-resistant organisms. High levels of carbapenem resistance were detected in K pneumoniae (72.8%) and A baumannii (92.6%), and A baumannii isolates showed high resistance to nearly all antibiotics tested. Extremely drug-resistant K pneumonia and A baumannii accounted for nearly 50% of the gram-negative isolates. While overall mortality in COVID-19 patients in the 10 hospitals was 11.6%, mortality among patients with secondary infections was 56.7%.

The study authors say the prevalence of highly resistant pathogens, and the fact that most of the infections were hospital-acquired suggests poor infection control practices and irrational use of broad-spectrum antibiotics. Most of the antibiotics prescribed came from the WHO's "watch" (52.4%) and "reserve" (22.1%) categories.

"These data were captured when the COVID-19 cases were on the rise, and the findings suggest that a lot of overprescribing of antimicrobials happened during that time," they wrote. "The practice of poor infection control and empirical over-use of broad-spectrum antimicrobials also provides fertile ground for future outbreaks with highly drug-resistant pathogens."
May 24 Infect Drug Resist study

Rapid test linked to quicker optimal therapy for blood infections

Originally published by CIDRAP News May 24

Implementation of a test that provides rapid bacterial identification and susceptibility results from positive blood cultures shortened the time to optimal antibiotic therapy and reduced unnecessary antibiotic exposure in hospitalized patients with bacteremia, researchers reported late last week in the Journal of Antimicrobial Chemotherapy.

The Improving Outcomes and Antibiotic Stewardship for patients with gram-positive bloodstream infections (IOAS) study, led by scientists from Accelerate Diagnostics (which also provided funding), evaluated clinical and antimicrobial stewardship metrics at two hospitals in Arkansas and Iowa following implementation of the Accelerate PhenoTest BC Kit (AXDX), a diagnostic platform that can identify bacteria from blood cultures and provide antimicrobial susceptibility testing (AST) results up to 40 hours faster than conventional methods.

The researchers analyzed two groups of patients with gram-positive bacteremia, one that underwent traditional identification and AST (pre-AXDX) and one that underwent testing with AXDX (post-AXDX). The primary outcome was time to optimal therapy (TTOT), and secondary outcomes included time to first antibiotic modification (overall and gram-positive antibiotics) and duration on unnecessary coverage for methicillin-resistant Staphylococcus aureus (MRSA).

A total of 219 patients with gram-positive bacteremia (109 pre-AXDX and 110 post-AXDX) were included in the study. The median TTOT was 36.3 hours in the pre-AXDX group and 20.4 hours in the post-AXDX group. Analysis of secondary outcomes showed that the median time to first antibiotic modification was also reduced in the post-AXDX patients (15.9 hours vs 29.1 hours), as was the median time to first gram-positive antibiotic modification (17.2 hours vs 33.2 hours) and the median duration of unnecessary MRSA coverage (29.7 hours vs 58.4 hours).

The researchers also observed a trend toward decreased acute kidney injury in the post-AXDX group compared with the pre-AXDX group (13% vs 24%) but found no differences in clinical outcomes such as mortality, Clostridioides difficile infection (CDI), and readmission to the hospital.

"In summary, implementation of AXDX offered a comprehensive solution to replace various identification and phenotypic testing methods and had a meaningful impact on the management of patients with Gram-positive bacteraemia in the IOAS study," the study authors wrote. "TTOT and initial antibiotic modifications were significantly faster, and patients received less unnecessary antibiotic therapy compared with conventional microbiology diagnostics."
May 22 J Antimicrob Chemother study

COVID-19 Scan for May 28, 2021

News brief

Children have more complications with COVID than with flu, study finds

Hospitalization, hypoxemia, pneumonia, and other complications were found more in children who contracted COVID-19 than in those who had seasonal flu, according to a study today in Pediatrics.

The researchers drew from databases in France, Germany, Spain, South Korea, and the United States to analyze data on 242,158 youth (18 years and younger) diagnosed as having COVID-19 from January to June 2020, 4.0% of whom were hospitalized. They then compared 30-day outcomes, including hospitalization, death, pneumonia, and multi-system inflammatory syndrome in children (MIS-C), with 2,084,180 children who had the flu during the 2017-18 season.

Among the COVID-19 patients, asthma was the most common comorbidity, ranging from 10.1% in Spain to 28.1% in the United States. Obesity was the second most common condition (1.9% in France; 19.0% in US). Health conditions were more prevalent among the hospitalized: For instance, in the US IQVIA-OpenClaims database, 34.1% had asthma, 29.7% had heart disease, 18.0% were obese, 14.0% had congenital malformations, and 9.3% had cancer.

In the two US databases covering about 2,300 hospitalized patients with no prior observation, 54.2% to 57.1% of 2,267 patients were 4 or under. In the three databases with hospitalized subgroups with 1 year of prior observation (one South Korean, two American), those percentages dwindled to 17.1% to 27.3% among roughly 7,500 children.

Hospitalization rates were higher for COVID-19 than for flu in all databases save one. For example, it was 3.5% versus 0.9%, 33.2% versus 7.4%, and 30.8% versus 3.7% in three US databases. In the OPTUM-EHR-US system, though, hospitalization rates were 7.6% for COVID-19 and 10.6% for flu.

"Overall, all outcomes were more frequent in children/adolescents with COVID-19 diagnosis than those with a diagnosis of seasonal influenza in 2017-2018, suggesting more severe disease prognosis in children with COVID-19 than influenza," the researchers write.

Despite this, the researchers said they were reassured that 30-day mortality was negligible and that particular complications were low, such as MIS-C : 0.5% to 3.1% in non-hospitalized groups but up to 7.6% in hospitalized groups. Because shortness of breath, loss of smell or taste, and gastrointestinal symptoms were more pronounced in the COVID-19 cohort than the flu cohort, they add that those symptoms may help with diagnosis.
May 28 Pediatrics study

Colchicine lowers hospitalization, death rate in COVID-19 outpatients

Outpatients with lab-confirmed COVID-19 who received colchicine had lower hospitalization and death rates than those given a placebo, according to a randomized, controlled trial yesterday in The Lancet Respiratory Medicine. The anti-inflammatory drug has been used for ailments such as gout, pericarditis, and coronary disease.

The phase 3 study consisted of 2,235 outpatients who took 0.5 milligrams (mg) of colchicine twice a day for 3 days, then once a day for 27 days. These were matched with 2,253 outpatients who received a placebo. Participants were enrolled a median of 5.3 days after symptom onset from Mar 23 to Dec 22, 2020, and they hailed from Brazil, Canada, Greece, South Africa, Spain, and the United States.

All participants were above 40 years and had at least one high-risk criterion, such as being above 70 or being obese. The median age was 53 years, and 55.4% were women.

Hospitalization and death were not linked significantly with the colchicine intervention overall, but when the analysis was narrowed to outpatients confirmed by polymerase chain reaction (PCR) tests, data showed a 25% reduced likelihood (4.6% vs 6.0%; 95.1% confidence interval [CI], 0.57 to 0.99 odds ratio).

Serious adverse events occurred in 4.9% of colchicine patients and 6.3% of placebo recipients. Pneumonia was less prevalent in the intervention group (2.9% vs 4.1%), but diarrhea was more common (13.7% vs 7.3%). Overall, the researchers say that 24.2% of adverse events in the colchicine group and 15.5% in the placebo group were related to the trial.

"Is colchicine likely to become a first-line treatment for community management of early COVID-19? The answer is probably not," Clark D. Russell, BmedSci, MBChB, of the University of Edinburgh, writes in a commentary. "This trial does however add proof of principle of two important therapeutic concepts—progression of COVID-19 lung injury can be inhibited to prevent hospital admission and anti-inflammatory therapy can achieve this."
May 27 Lancet Respir Med study and commentary
Feb 5 CIDRAP News scan on small colchicine study

Black people have less trust in medicine, COVID vaccines, survey says

A survey of 1,835 Michigan residents found higher levels of medical mistrust and lower levels of COVID-19 vaccine acceptance in Black people, according to a JAMA Network Open study yesterday.

The survey was conducted from June to December 2020 with a convenience sample. Most respondents (79.3%) were women, and 52.4% were White. Black people made up the second largest racial/ethnic group, with 21.5%. Participants' mean age was 49.4 years, and they were fairly split between three income levels.

Overall, 75.0% reported a low willingness to participate in COVID-19 vaccination trials, and 51.5% had a low willingness to receive the vaccine in general. Black people displayed the most medical mistrust among the racial/ethnic groups: On a Likert scale where 1 was "definitely yes" and 5 was "definitely no," the mean value for medical trust was 1.84, but Black people reported 2.35, followed by Hispanic people (who made up 4.6% of respondents), with 2.22.

Less vaccine trial rejection was found among men, those with lower medical mistrust scores, and those with at least a college degree. Those with income less than $35,000 a year were more likely to reject COVID-19 vaccines in general compared with those who made $35,000 to $75,000.

"In this survey study, racial/ethnic group-based medical mistrust partially mediated the association between Black race and lower acceptance of COVID-19 vaccine trial participation and actual vaccination," the researchers write.
May 27 JAMA Netw Open study

News Scan for May 28, 2021

News brief

GARDP urges nations to strengthen response to drug resistance

GARDP also said member states should ensure that low- and middle-income countries are equal partners in a comprehensive global response.
May 26 GARDP statement

Pennsylvania confirms CWD on hunting preserve near New York border

A white-tailed deer on a Warren County, Pennsylvania, hunting preserve—located in the northwestern part of the state just 5 miles from New York state—has tested positive for chronic wasting disease (CWD), a fatal prion disease that affects cervids like deer, elk, and moose.

"Pennsylvania has taken CWD very seriously, taking aggressive steps to contain the disease, using a scientific, fact-based approach," said Pennsylvania State Veterinarian Kevin Brightbill, DVM, in a PA Media press statement. "We will continue to investigate and implement rigorous controls on any business whose deer may have been exposed, and we are working with New York state regulatory partners to mitigate the threat."

According to the Pennsylvania Department of Agriculture, remaining deer at the hunting preserve were euthanized and CWD was not detected in any of the samples. The preserve is under quarantine for 5 years.

The state also said the detection will prompt a new CWD Disease Management Area (DMA) established in Warren County, which means it will be illegal to rehabilitate injured deer, possess or use cervid urine–based attractants, and feed free-ranging deer in that zone.
May 27 PA Media press release

Variant H1N2 flu case reported in Ohio child

The Centers for Disease Control and Prevention (CDC) today reported a variant H1N2 (H1N2v) infection in an Ohio child, marking the nation's first such case of the year.

In its weekly FluView report, the CDC said the child, whose age was not reported, was not hospitalized and has recovered from his or her illness. The investigation found that the patient lives on a farm where pigs are present. No human-to-human transmission was found.

Sporadic H1N2v cases have been reported in North America, including Canada, and in other countries such as Brazil.

The US reported its last H1N2v cases in 2018, when 13 infections were reported in the summer across three different states. Nearly all involved swine exposure at fairs at which closely related swine H1N2 viruses were found. One patient had no links to fairs or pig exposure, hinting at possible human-to-human transmission. The new illness lifts the US H1N2v total to 26.
May 28 CDC FluView report
CDC background

Six African countries report more vaccine-derived polio cases

Six African nations reported more polio cases this week, all involving vaccine-derived types, according to the latest weekly update from the Global Polio Eradication Initiative (GPEI).

Burkina Faso reported a circulating vaccine-derived poliovirus type 2 (cVDPV2) case from Dori in the country's northeast, its first case of 2021. The Republic of Congo also reported one cVDPV2 case, its second of the year, involving a patient in Niari department in the west.

Meanwhile, the Democratic Republic of the Congo (DRC) reported five more cases in three provinces—South Ubangi, North Ubangi, and Mongala—putting its total at seven for the year. Guinea reported one more case, with no details. Mali reported another cVDPV2 case, which involves a patient from Kayes in the west and is included in its total for 2020, which is now 48.

In another development, Madagascar reported 3 circulating vaccine-derived poliovirus type 1 (cVDPV1) cases, 2 in Boeni and 1 in South East, lifting its 2021 total to 4.
May 27 GPEI update