News Scan for Aug 13, 2021

News brief

Higher COVID-19 transmission tied to crowded households

COVID-19 transmission among households was three times more likely if the household had a high living density, according to a study yesterday in Clinical Infectious Diseases. Higher living density is defined as having more than three household members but fewer than six rooms.

The researchers looked at 100 COVID-19 index patients, all adults, and household contacts of all ages from April to October 2020 in North Carolina. Participants were enrolled in the study a median of 6 days after the index patient's symptom onset or diagnosis. On days 7, 14, and 21 from symptom onset, the household submitted nasal swabs, and on day 28, they underwent a seroconversion test, although the researchers note that 38% of households did not have complete participation.

Overall secondary attack rate was 32% (95% confidence interval [CI], 22% to 44%). However, it was higher in households with high living density (51% vs 19%), indicating that those members were 3.3 times more likely to get COVID-19 (95% CI, 1.02 to 10.9). The researchers say this could be a factor in the disproportionate effect of COVID-19 among minorities. For instance, in their cohort, 42% of non-White index patients lived in a higher living density situation vs 12% of White index patients.

"Households with non-White index cases were more likely to experience incident transmission in the household, despite there being no difference in index case viral loads by race/ethnicity," the researchers write. "Household crowding in the context of high-inoculum infections may amplify the spread of COVID-19, potentially contributing to disproportionate impact on communities of color."

The researchers were unable to assess associations with age, mask-wearing, and symptoms during transmission, nor did they analyze index case viral loads.
Aug 12 Clin Infect Dis study

Significant decline noted in outpatient antibiotic use in British Columbia

Outpatient antibiotic use in British Columbia has declined by more than 23% over the last two decades, driven by significant decreases in pediatric use, Canadian researchers reported yesterday in JAC-Antimicrobial Resistance.

The retrospective cohort study looked at all antibiotic prescriptions extracted from BC PharmaNet, a centralized database linked to all pharmacies in the province, from 2000 to 2018. The study period included 5 years prior to the 2005 launch of the Community Antimicrobial Stewardship (CAS) program, a province-wide effort to educate the public about judicious antibiotic use and encourage stewardship. Researchers examined overall oral antibiotic use, antibiotic use by class and age, and trends over time to evaluate the impact of the program.

More than 51 million outpatient antibiotics were dispensed over the study period, at an overall average rate of 609 prescriptions per 1,000 population. Outpatient prescribing declined by 23.1%, from 652 to 503 prescriptions per 1,000 population. Declining use was observed for penicillins (–27%), macrolides (–43%), sulphonamides and trimethoprim (–58%), quinolones (–22%), and other beta-lactams (–12%). The sharpest declines were seen among pediatric patients, with a negative association between increasing age and decreasing magnitude of antibiotic reduction. Upper respiratory tract infections were the most prescribed indication in 2018.

The analysis found that antibiotic prescribing for common infections declined by 4% (rate ratio [RR], 0.96; 95% confidence interval [CI], 0.96 to 0.97) from 2005 to 2013 (era 1) compared with the pre-stewardship period. From 2014 to 2018 (era 2), when a focus on judicious prescribing for urinary tract infections was added to the CAS, prescribing declined by 24% (RR, 0.76; 95% CI, 0.76 to 0.76) compared with the pre-stewardship period. Antibiotic prescribing for children 0 to 2 years of age declined by 54% (RR, 0.46; 95% CI, 0.46 to 0.46) in era 2, while prescribing in patients over 80 increased by 12% (RR, 1.12; 95% CI, 1.11 to 1.12).

"Although this study cannot attribute causation, a substantial decline in antibiotic use was observed in our 19 year study period, with temporal correlations between targeted stewardship eras and related optimizations in antibiotic use," the study authors wrote. "Despite this progress, prescribing in our eldest cohorts is increasing, and optimizing prescribing to our most vulnerable population remains a provincial target."
Aug 12 JAC-Antimicrob Resist study

Study shows zanamivir might be most effective antiviral for influenza

For healthy adults and children, zanamivir may be the most effective antiviral used to shorten the duration of influenza symptoms, according to a new study in JAMA Network Open.

The study reviewed 26 trials that looked at antiviral drugs at high or low doses. The trials included 11,897 participants with a median age of 32.5, and 52.9% of them were men. Primary outcomes were the time to alleviation of influenza symptoms (TTAS), complications of influenza, and adverse events (total adverse events, nausea, and vomiting).

The studies measured how well flu was treated with neuraminidase inhibitors (oseltamivir, peramivir, zanamivir, or laninamivir) or an endonuclease inhibitor (baloxavir), compared with a placebo.

High-quality evidence showed zanamivir, commonly known by the brand name Relenza, as associated with the shortest TTAS (hazard ratio, 0.67; 95% CI, 0.58-0.77), while baloxavir was associated with the lowest risk of influenza-related complications (risk ratio [RR], 0.51; 95% CI, 0.32-0.80.). But the evidence for baloxavir was of moderate quality. Baloxavir had the lowest risk of total adverse events.

"To our knowledge, this is the first study to simultaneously compare the efficacy of baloxavir and 3 neuraminidase inhibitors, the 4 drugs most commonly used for patients with influenza in current clinical practice," the authors said. "Network meta-analysis studies such as this may have utility in informing treatment guidelines for viral conditions, like influenza, when few direct comparisons between individual therapies are available."
Aug 13 JAMA Netw Open study

Three African nations report more vaccine-derived polio cases

Three African countries reported more polio cases this week, all involving circulating vaccine-derived poliovirus type 2, the Global Polio Eradication Initiative (GPEI) said in its latest weekly update.

Ethiopia reported 1 case, which involves a patient from Oromiya state in the central part of the country, bringing its total for the year to 7. Mali reported 2 cases, one in Mopti and the other in Sikasso, which are included in its 2020 total—now at 50.

Also, Nigeria reported 3 new cases in different states: Kebbi, Nasarawa, and Rivers. The country now has 68 cases this year.
Aug 12 GPEI weekly update

ASP Scan (Weekly) for Aug 13, 2021

News brief

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

Significant decline noted in outpatient antibiotic use in British Columbia

Study of internet searches finds public AMR awareness lagging

Originally published by CIDRAP News Aug 12

An analysis of Google Trends suggests World Antimicrobial Awareness Week has not improved public awareness of antimicrobial resistance (AMR).

In a study published yesterday in the International Journal of Infectious Diseases, researchers analyzed trends in the search volume of the terms "antimicrobial resistance," "antibiotics," and "antibacterials" in Japan, the United States, the United Kingdom, and worldwide from 2015—when World Antimicrobial Awareness Week was introduced—through 2020. Using relative search volume (RSV) on Google Trends as a surrogate, they performed a joinpoint regression analysis to identify a statistically significant time point of a change in trend.

The results showed that World Antibiotic Awareness Week did not have a significant impact on general public interest in AMR or antibiotics in Japan, the United States, or the United Kingdom, although some increase in RSV was noted worldwide in 2017 and 2020. In addition, the RSV for antibiotics in every country or region significantly declined in 2020 during the COVID-19 pandemic.

"This study implies that we need to develop a more effective method to improve public awareness to fight against AMR," the study authors concluded.
Aug 11 Int J Infect Dis study

Dutch paper: Antibiotics in hospital wastewater a growing problem

Originally published by CIDRAP News Aug 12

A new white paper by Dutch experts is calling for solutions to the problem of antimicrobial residues and resistant bacteria in hospital wastewater.

Citing data from recent research in the Netherlands, the paper from the Dutch Consortium on Antibiotics and Pharmaceutical Residues from Water estimates that 40% of antibiotic residues in the country's wastewater originates from Dutch hospitals, exposing bacteria in the water to concentrations of antibiotics—many of them "last-resort" antibiotics—that are high enough to promote resistance but not high enough to kill the bacteria. The resistant bacteria can then pass on their resistance to other bacteria through the transfer of plasmids that harbor resistance genes.

To address this problem, the consortium calls for a three-pronged approach that removes the antibiotic residues from the water, disinfects the treated water, and removes plasmids containing the resistance genes—both at the source (hospitals) and through "end-of-pipe" solutions at sewage treatment facilities. While many sewage treatment facilities are able to remove antibiotics residues from treated water, additional purification techniques will be needed to remove plasmids, the authors of the paper note.

"In other words: we will not prevent AMR if only the antibiotic residues are removed from wastewater," they write. "We will have to do more."

The authors say the problem demands a targeted joint approach and calls for cooperation between hospitals, water companies, the pharmaceutical sector, and the government.
Aug 10 Dutch white paper

Canadian surveillance shows rise in multidrug-resistant pathogens

Originally published by CIDRAP News Aug 11

The proportion of multidrug-resistant Escherichia coli and Klebsiella pneumoniae found in Canadian hospital patients increased substantially from 2007 through 2018, according to a surveillance study published today in the Journal of Antimicrobial Chemotherapy.

The findings are from an analysis of bacterial isolates collected through CANWARD, an ongoing national surveillance study that analyzes isolates from hospitals in 8 of Canada's 10 provinces for antibiotic resistance. Researchers conducted antimicrobial susceptibility tests to confirm phenotypic resistance and performed whole-genome sequencing to detect production of extended-spectrum beta-lactamase (ESBL) enzymes, which confer resistance to multiple antibiotic classes.

Of the 9,588 E coli isolates collected from 2007 through 2018, 7.0% (671) were ESBL producers, and the proportion of ESBL-producing E coli climbed from 3.3% in 2007 to 11.2% in 2018. Of the 3,056 K pneumoniae isolates collected, 4.6% (141) were ESBL producers; the proportion of ESBL-producing K pneumoniae rose from 1.3% to 9.3%. Overall, 97.2% of ESBL-producing E coli and K pneumoniaewere multidrug-resistant (MDR). The most common ESBL enzyme in E coli (62.3% of isolates) and K pneumoniae (48.9%) was bla_CTX-M-15.

The most frequent sequence types (STs) were ST131 for E coli (62.4%) and ST11 (7.8%) and ST147 (7.8%) for K pneumoniae.

"Increases in the proportion of infections caused by ESBL-producing Enterobacteriaceae, especially specific STs, are detrimental to patient care and public health because they result in increased use of carbapenems, which may in turn drive the emergence and increased isolation of carbapenem-resistant Enterobacteriaceae," the authors write. "Prospective surveillance of these evolving MDR pathogens is imperative."
Aug 11 J Antimicrob Chemother abstract

UN, India team up to boost understanding of AMR in the environment

Originally published by CIDRAP News Aug 11

The United Nations Environmental Programme (UNEP) has launched a collaboration with Indian researchers to address the environmental dimension of AMR.

The collaboration between UNEP and the Indian Council of Medical Research aims to strengthen the environmental aspects of national- and state-level AMR action strategies and plans, according to a UNEP press release. It will conduct secondary research and stakeholder consultations to better understand the role the environment plays in harboring and transmitting resistant pathogens.

Among the areas the project will likely explore is the effects of discharging antibiotics and other antimicrobial compounds into natural environments, which has the potential to drive the evolution of resistant bacteria. India is a major manufacturer of antibiotics, and studies have found high concentrations of antibiotics and high levels of AMR genes in waterways in and around Hyderabad, the country's pharmaceutical manufacturing hub.

"AMR in the environment is an issue inadequately recognized by the stakeholders," said Lav Aggarwal, a member of India's Ministry of Health and Family Welfare. "It is critical to understand that we have to engage with the environment as a critical part of our AMR response."
Aug 9 UNEP press release

Study finds high number of AMR genes in healthy Vietnamese kids, adults

Originally published by CIDRAP News Aug 10

A small genomic study in Vietnam found a high abundance of AMR genes in the gut microbiomes of healthy adults and children, with very young children having the highest abundance, researchers reported today in the Journal of Infectious Diseases.

Hypothesizing that the gut microbiome could be a major reservoir of AMR genes in Vietnam, a country with high rates of resistant pathogens, the researchers performed shotgun metagenomic sequencing on 42 fecal samples from 21 children and 21 adults in Ho Chi Minh City. Participants had no known viral, bacterial, or parasitic gastrointestinal infection, no record of diarrheal episodes in the previous 6 months, and no antimicrobial use in the previous 3 months. Participants were separated into three groups for analysis: 0 to 23 months, 2 to 5 years, and adults.

In total, 132 AMR genes were identified, with MLS (macrolide, lincosamide, and streptogramin) and tetracycline resistance genes identified in more than 95% of samples, and 48 different beta-lactamase genes identified. Several genes associated with extensively drug-resistant pathogens, including the bla_CTX-Mgene, were detected. An overall comparison of AMR gene abundance found that children in the 0 to 23-month group displayed lower microbial diversity but possessed a greater number of AMR genes compared with the other age groups, with a median number 31 AMR genes, compared with 25 in the 2 to 5-year-old group and 21 in the adults.

The study authors suggest that children under 2 may have the highest abundance of AMR genes because they are the most likely to receive antimicrobials when ill and the most likely to be infected with an enteric pathogen.

"Our data highlight the high abundance of AMR genes in the gut microbiome of healthy adults and children, which may play a role in driving antibiotic resistance in enteric pathogens," they write. "We need to better understand the mechanisms driving microbial diversity and the selective pressure maintaining resident AMR genes in those from LMICs [low- and middle-income countries]."
Aug 10 J Infect Dis abstract

Survey examines caregiver attitudes on antibiotic use

Originally published by CIDRAP News Aug 9

A survey of US caregivers found that more than 1 in 10 either planned or had already administered a nonprescription antibiotic (NPA) to their child, researchers reported last week in the Journal of the Pediatric Infectious Diseases Society.

Among the 396 caregivers of children younger than 18 who answered all the questions in the survey, which was conducted from January 2019 through July 2019, 119 (30%) caregivers requested antibiotics from a clinician, 65 (16%) reported storing antibiotics currently in the home, and 47 (12%) reported intent to use an antibiotic without a clinician's directive or had already done so. Amoxicillin was the most common antibiotic stored in the home, followed by amoxicillin/clavulanate, cephalexin, and ciprofloxacin.

Further analysis of the respondents in the NPA group found that 40% reported requesting antibiotics from a clinician, and those with an annual income of over $75,000 were more than twice as likely as other caregivers (odds ratio, 2.04; 95% confidence interval [CI], 1.01 to 4.14) to store and use antibiotics without a clinician's directive. Nineteen percent of the NPA group agreed with the statement "It's okay to use antibiotics that were given to a friend or family member as long as it was used to treat a similar illness," compared with 3% of other caregivers.

"Our data highlight that the issue of antibiotic misuse by caregivers of children is complex and must be tackled systematically," the study authors wrote. "Future antibiotic stewardship efforts should include education for clinicians, pharmacists, and the public about leftover medication and nonprescription antibiotic use."
Aug 7 J Pediatric Infect Dis Soc abstract

Study finds COVID surges linked to increase in hospital infections

Originally published by CIDRAP News Aug 9

An analysis of US hospital data found that surges in COVID-19 hospitalizations were associated with elevated rates of healthcare-associated infections (HAIs) and drug-resistant pathogens, researchers reported today in Clinical Infectious Diseases.

Using data collected from 148 hospitals in 17 states from March through September 2020, the researchers found that increased relative rates of central line-associated bloodstream infections (CLABSIs), catheter-associated urinary tract infections (CAUTIs), and methicillin-resistant Staphylococcus aureus (MRSA) bacteremia increased as the COVID-19 burden increased.

Over 7 months, there were 60% more CLABSIs, 43% more CAUTIs, and 44% more cases of MRSA bacteremia than expected based on predicted HAIs had there been no COVID-cases.

Microbiology data from a subset of 81 hospitals with microbiology and cluster data through December 2020 confirmed those findings. Over 10 months, COVID-19 surges were temporally associated with a 24% increase in hospital-onset bloodstream infections and multidrug-resistant organisms, including a 30% increase in hospital-onset MRSA infections, a 44% increase in hospital-onset vancomycin-resistant Enterococci infections, and 27% increase in infections caused by multidrug-resistant gram-negative organisms. In addition, clusters of hospital-onset pathogens increased as the COVID-19 burden increased.

The findings support the researchers' hypothesis that routine HAI prevention practices, such as central line and urinary catheter care, may have been negatively impacted by disruptions to infection prevention and control measures during the pandemic.

"Although the per-patient risk of a hospital-onset infection remained very low, HAI rates increased during COVID-19 surges," the study authors write. "Further research is necessary to elucidate the specific ways in which the COVID-19 burden is affecting HAI rates, but our results identify a need to build capacity in infection prevention and control."
Aug 9 Clin Infect Dis abstract