ASP Scan (Weekly) for Jul 02, 2021

News brief

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

Intervention linked to reduced prescribing for respiratory infections

A provider-focused antibiotic stewardship intervention was associated with reduced antibiotic prescribing for respiratory tract infections (RTIs) at 31 primary care practices, with no impact on prescribing for infections that require antibiotics, researchers reported today in Clinical Infectious Diseases.

The intervention, implemented in the University of Pennsylvania Healthcare System in October 2017, consisted of a one-time educational session on appropriate prescribing for RTIs and patient communication strategies, along with monthly electronic feedback to providers on their prescribing performance for respiratory tract diagnoses (RTDs). Feedback was based on metrics that grouped RTDs into three tiers of appropriateness: tier 1 (antibiotic almost always indicated), tier 2 (may be indicated), and tier 3 (rarely indicated).

To assess the impact of the intervention, researchers conducted a stepped-wedge cluster randomized study comparing the proportion of patient visits with antibiotic prescriptions before and during the intervention.

Across 30 practices and 185,755 unique office visits, the proportion of visits with an antibiotic prescription declined from 35.2% pre-intervention to 23% during the intervention period. In a multivariable analysis, the intervention was associated with reduced odds of antibiotic prescribing for tier 2 diagnoses (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.52 to 0.62) and tier 3 diagnoses (OR, 0.57; 95% CI, 0.53 to 0.61), but not for tier 1 diagnoses (OR, 0.98; 95% CI, 0.83 to 1.16).

"This differential impact suggests that the study intervention was able to reduce inappropriate antibiotic prescribing without adversely impacting appropriate prescribing," the authors wrote. They add that assessing the sustainability of the intervention, along with patient outcomes and any unintended negative outcomes, will be important.
Jul 2 Clin Infect Dis abstract

Antibiotic sales increased during India's first COVID wave

India saw a significant increase in sales of non–child-appropriate formulation (CAF) antibiotics during the first wave of the COVID-19 pandemic, Indian researchers reported yesterday in PLOS One.

Using an interrupted time series (ITS) design, the researchers examined sales volumes of total antibiotics, azithromycin alone, and hydroxychloroquine in India's private sector from January 2018 to December 2020. They focused on non-pediatric formulations and adjusting to seasonal and non-seasonal trends as well as the effects of the lockdown.

India's unregulated private sector accounts for 75% of healthcare delivery and 90% of antibiotic sales in the country, leading to speculation that the surge in patients seeking care for COVID-19 may have led to increased sales of antibiotics, particularly azithromycin, which was being used in combination with hydroxychloroquine in many countries during the early months of the pandemic.

More than 16.2 million doses of antibiotics were sold in India in 2020, which is slightly less than the amount in 2018 and 2019. But the proportion of non-CAF antibiotics rose from 72.5% in 2019 to 76.8% in 2020, and the ITS analysis found that COVID-19 likely contributed to 216.4 million excess doses of non-CAF antibiotics and 38 million excess doses of non-CAF azithromycin from June through September 2020 (after the lockdown and until the first wave peak).

The study authors say the findings have important implications for global antimicrobial resistance, particularly in low- and middle-income countries (LMICs), where overuse of antibiotics is common and similar patterns of antibiotic use among presumptive or confirmed COVID-19 cases likely exist. They also note that if antibiotic use followed the same pattern during India's second wave of COVID-19, which was substantially more devastating, the impact could be even worse.

"Policy makers in India and other LMICs should recognize this substantial overuse of antibiotics induced by COVID-19," they wrote. "Considering the ongoing trends, the very low vaccination coverage level, and the amount of time necessary to eventually vaccinate the entire population, immediate action is needed to reduce the overuse of antibiotics for COVID-19."
Jul 1 PLOS One study

Global prevalence of vanco-resistant Staph has more than tripled: study

Originally published by CIDRAP News Jul 1

The global prevalence of vancomycin-resistant Staphylococcus aureus (VRSA) has more than tripled in the past two decades, according to a systematic review and meta-analysis yesterday in Antimicrobial Resistance & Infection Control.

The review of 62 published studies on VRSA prevalence rates, conducted by a team of Chinese and Iranian researchers, found that prevalence increased from 2% of 466 isolates before 2006 to 6% of 6,692 isolates from 2006 through 2014 and 7% of 5,798 isolates from 2015 through 2020. Prevalence was highest in Africa (16%) and Asia (5%), followed by North America (4%), South America (3%), and Europe (1%). The frequencies of VRSA isolates from clinical, non-clinical, and mixed samples were 6%, 7%, and 14%, respectively.

Analysis of the genetic backgrounds of VRSA strains found that 71% and 26% were positive for vanAand vanB resistance genes, respectively, and 4% contained the vanC1 gene.

The first case of VRSA, which tends to be multidrug-resistant, was reported in 2002. The study authors suggest the increased prevalence and detection of VRSA could be attributed to more frequent use of vancomycin for treatment of methicillin-resistant S aureus infections, better diagnostics, and a change in vancomycin resistance breakpoints since 2006.

"This study clarifies that the rigorous monitoring of definite antibiotic policy, regular surveillance/control of nosocomial-associated infections and intensive surveillance of vancomycin-resistance are required for preventing emergence and further spreading of VRSA," they wrote.
Jun 30 Antimicrob Resist Infect Control study

AHRQ publishes antibiotic stewardship toolkit for long-term care

Originally published by CIDRAP News Jun 29

The Agency for Healthcare Research and Quality (AHRQ) yesterday released a toolkit to improve antibiotic use in long-term care facilities.

The toolkit consists of presentations, slides, posters, and other documents that provide guidance on how to create a culture of safety around antibiotic prescribing, develop and improve antibiotic stewardship programs, and learn and disseminate best practices for common infectious disease syndromes in long-term care settings. It also includes an explanation of the "Four Moments of Antibiotic Decision Making," a step-by-step approach that clinicians can use to achieve optimal antibiotic prescribing.

This is the third antibiotic stewardship toolkit published by AHRQ, which has also developed them for acute care hospitals and ambulatory care settings.

The toolkit is based on the experiences of more than 400 US hospitals that took part in AHRQ's Safety Program for Improving Antibiotic Use, a 5-year project to improve stewardship and antibiotic prescribing in acute care, ambulatory care, and long-term care facilities across the country.
Jun 28 AHRQ toolkit

Thai hospital study finds alarming levels of critical antibiotic resistance

Originally published by CIDRAP News Jun 29

A large-scale surveillance study of hospitals in Thailand found high levels of critical antibiotic resistance in clinically important gram-negative bacteria, researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

The analysis of 187,619 isolates of four gram-negative bacterial species (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii complex [ABC], and Pseudomonas aeruginosa) submitted by 47 hospitals found that 50% were critically drug-resistant. E coli was the most commonly isolated bacteria. The prevalence of extended-spectrum cephalosporin resistance was higher in E coli than in K pneumoniae, but carbapenem resistance was 4.5-fold higher in K pneumoniae (17.2%) than in E coli (3.8%). Critical drug resistance in ABC ranged from 66.4% to 78.7% across all specimens, with 41.9% of isolates found to be extensively drug-resistant (XDR) and 35.7% multidrug-resistant (MDR).

Molecular analysis of 12,915 isolates found that the blaCTX-M, blaNDM, and blaOXA-48-like resistance genes were prevalent among extended-spectrum cephalosporin-resistant and carbapenem-resistant E coli and K pneumoniae, while blaOXA-23-like was the most common carbapenemase gene in XDR/MDR A baumannii, and blaIMP was the most common in XDR/MDR P aeruginosa.

The study authors note that carbapenem resistance in E coli and K pneumoniae has more than tripled in Thailand in less than a decade and is now significantly higher than in other Southeast Asian countries. They link the increase to inappropriate prescribing of carbapenems in the country's hospitals, and suggest that widespread over-the-counter antibiotic use is playing a role in rising resistance to other antibiotics.

"The threat of bacterial resistance should be critically addressed in Thailand and in the region for the necessity of appropriate antimicrobial prescription in clinical practice," they wrote. "In addition, the public policy regarding the self-consumption of antibacterial agents should be emphasized to reduce the risk of acquiring drug-resistant infections."
Jun 28 Antimicrob Agents Chemother abstract

Chinese study finds lower prevalence of MCR-1 in healthy residents

Originally published by CIDRAP News Jun 28

The prevalence of the colistin-resistance gene MCR-1 in healthy residents of a Chinese city declined following China's ban on colistin as a growth promoter in livestock in 2017, researchers reported today in Clinical Microbiology and Infection. But seafood may be an emerging risk factor for MCR-1 colonization.

In a study led by researchers from the Shenzhen Center for Disease Control and Prevention, 719 healthy volunteers from Shenzhen were recruited from March 2018 through December 2019 to investigate the prevalence of MCR-1, a mobile gene that confers resistance to the last-resort antibiotic colistin, in the human intestine. Researchers collected fecal samples from the volunteers, then conducted whole-genome sequencing to detect the presence of the gene. They also conducted a case-control study to determine risk factors for MCR-1 positivity.

Overall, 56 samples (7.8%) were positive for MCR-1, with the prevalence of MCR-1 significantly higher among volunteers enrolled in 2018 (11.5%) than among those enrolled in 2019 (2.4%). All isolates containing the gene were E coli. Analysis of risk factors for MCR-1 positivity showed that pork and chicken meat were no longer a risk factor, but a higher intake of seafood (more than 75 grams per day) was associated with a higher risk of MCR-1 carriage (OR, 2.18; 95% confidence interval [CI], 1.05 to 4.52). Increased intake of whole grains (more than 150 grams per day) was associated with a lower risk of MCR-1 carriage (OR, 0.05; 95% CI, 0.004 to 0.58).

The study authors theorize that the significant decline in colistin use in livestock following the 2017 ban resulted in significantly less MCR-1–positive bacteria in animal-derived food. The ban on the use of colistin as a growth promoter came after researchers first identified MCR-1 in Chinese pigs, pork products, and people in 2015. But colistin is still used for treating sick animals in China, and the authors suggest that colistin- and MCR-1–contaminated manure may be getting into waterways and spreading into aquaculture.

"Aquaculture is considered as a significant reservoir and a potential origin of mobile colistin resistance," they wrote. "Hence, a complete surveillance system for antimicrobial resistance in aquatic environment, especially colistin resistance, should be established."
Jun 28 Clin Microbiol Infect study

Stewardship / Resistance Scan for Jul 02, 2021

News brief

Intervention linked to reduced prescribing for respiratory infections

Antibiotic sales increased during India's first COVID wave

India saw a significant increase in sales of non–child-appropriate formulation (CAF) antibiotics during the first wave of the COVID-19 pandemic, Indian researchers reported yesterday in PLOS One.

News Scan for Jul 02, 2021

News brief

Pain associated with worse COVID-19 in sickle cell disease

A history of pain in sickle cell disease (SCD) patients—the disease's most common complication—is associated with worse COVID-19 outcomes in children and adults, according to a Blood Advances study yesterday. SCD-related organ comorbidities were also related to worse COVID-19 outcomes in children.

The researchers looked at 750 international patients with COVID-19 and SCD from March 2020 to 2021. Almost half (48.5%) were children, median age 11, and the remaining were adults, median age 31. About 91% were Black and 7% were Latino.

Most had prior acute care visits for pain (55.5% children, 78.5% adults), and almost one in three had acute chest syndrome in the previous 3 years (29.4% children, 29.5% adults). The most common COVID-19 symptoms were pain (35.2% children, 67.4% adults) and acute chest syndrome (14.8% children, 29.5% adults), which made the researchers question if COVID infection triggered pain episodes.

Data showed that in children, their risk of severe COVID-19 increased with renal comorbidities (risk ratio [RR], 3.67), a history of pain (RR, 3.09), or heart or lung comorbidities (RR, 1.76), with the latter two conditions also connected with increased hospitalization risk (RRs, 2.15 and 1.61, respectively). In adults, the risk of COVID-19 severity increased with a history of pain (RR, 1.94).

Half of the patients were on hydroxyurea, a drug meant to reduce pain episode frequency, but the researchers did not find a link with COVID-19 hospitalization or severity. It was, however, associated with a lower risk of pain in adults.

"This study tells us that all individuals with sickle cell disease are not at equal levels of risk," said study author Lana Mucalo, MD, of the Medical College of Wisconsin, in an American Society of Hematology (ASH) press release. "Patients with a history of pain, as well as individuals with coexisting organ conditions, need to be even more careful to avoid COVID-19 infection than those without any comorbidities."
Jul 1 Blood Adv study
Jul 1 ASH press release

COVID risk from patient encounters appears low in emergency responders

COVID incidence for emergency medical service (EMS) workers was not affected by work encounters with a COVID-19 patient, according to an Emerging Infectious Diseases study yesterday.

The researchers looked at EMS responses in King County, Washington, from Feb 16 to Jul 31, 2020, and found that about 1% of all encounters were with a COVID-19 patient (1,115), of which about one in six needed an aerosol-generating procedure (AGP), the most common being nonrebreather masks. (Over the study period, EMS workers received COVID-related protocols, including personal protective equipment guidelines. For instance, anytime an AGP was performed, the workers needed to don N95 respirators.)

By the end of the study period, 30 workers had tested positive for COVID-19, with only one linked with a COVID-19 patient encounter within the patient's incubation period(the patient had also needed at least one AGP). As for the other workers, 18 received positive diagnoses outside of their most recent COVID-19 patients' incubation period, and 11 never encountered a COVID-19 patient through work. EMS worker incidence for COVID-19 infection acquired anywhere was 0.57 infections per 10,000 person-days, and no significant change of incidences were attributed to a COVID patient encounter or not.

"We observed that the large majority of COVID-19 illness was a consequence of encounters not with patients but in the community or occupational settings," the researchers write. "These findings support efforts to screen workplaces for provider symptoms or initiate point-of-care provider testing to limit on-the-job exposure as well as to practice guideline-directed social distancing, masking, and hygiene recommendations outlined for the general public, acknowledging that vaccination may affect these directives."

Overall, about 55% of the region's first responders had contact with a COVID-19 patient, and while this includes patients beyond their transmission period, one third also didn't display common symptoms. Across 8,582 person-days, 705 EMS workers performed at least one AGP on COVID-19 patients within their viral incubation period, and across 26,583 person-days, 1,389 workers treated a COVID-19 patient within their incubation period who did not need an AGP.
Jul 1 Emerg Infect Dis study

FDA announces plan to prevent Cyclospora-related foodborne disease

The Food and Drug Administration (FDA) yesterday published a new prevention, response, and research action plan to help the agency prevent Cyclospora contamination of foods, and respond quickly to outbreaks.

Cyclospora is a parasite that can cause intestinal illness in people when ingested. It was first identified in domestically grown herbs in the United States in 2018. Since then, infections have been rising, and there have been 6,000 domestically acquired cases of Cyclospora over the past 3 years.

"Given the emerging nature of Cyclospora contamination in domestic produce, a large number of action items in this plan are aimed at addressing knowledge gaps," the FDA said. The FDA created a Cyclospora Task Force in 2019, and that group authored the new action plan. In a press release, the FDA said the plan is modeled after the Leafy Greens Shiga toxin–producing Escherichia coli (STEC) Action Plan.

The plan expands laboratory capacity across the FDA, state, foreign partners and academia to sample and test for Cyclospora, the FDA said. The FDA will also work with the Centers for Disease Control and Prevention to better understand the case distribution of cyclosporiasis across the country.
Jul 1 FDA plan and press release

Nigeria reports 10 more vaccine-derived polio cases

Only one country reported new polio cases this week: Nigeria, which reported 10 infections involving circulating vaccine-derived poliovirus type 2 (cVDPV2), according to the latest weekly update from the Global Polio Eradication Initiative (GPEI).

Of its cases, 3 are in Jigawa state, 3 in Yobe, and 1 each in Borno, Kano, and Zamfara states, boosting the country's total for the year to 21 cases.

Nigeria's total for 2021 has already passed the 8 cases reported for all of 2020.
Jul 1 GPEI update

Maine confirms its first Powassan virus case of the year

Health officials in Maine this week reported the state's first Powassan virus case of the year, which involves a resident of Waldo County, located in the east central part of the state.

In a statement, the Maine Department of Health and Human Services (MDHHS) said the person contracted the virus in Maine and is recovering after spending time in the hospital. The detection marks Maine's ninth Powassan virus case since 2010.

Powassan virus is spread by ticks, and infections are rare, with the United States averaging about 25 cases a year. There is no treatment for the illness, which can be severe. Symptoms range from headache to fever to encephalitis.
Jun 29 MDHHS statement