January 24, 2022
AMR is a leading cause of death worldwide, primarily affecting low-resource settings. In the most comprehensive assessment of the global AMR burden to date, researchers analyzed 471 million individual records or isolates from 23 pathogens and 88 pathogen-drug combinations across 204 countries. Predictive statistical modeling estimates approximately 1.27 million deaths attributable to bacterial AMR in 2019, revealing AMR as a leading cause of death from an infection after COVID-19 and tuberculosis. Although data comes primarily from high-income countries, low resources settings seem to carry the highest burden, with western sub-Saharan Africa having the highest AMR attributed death rates at 27.3 deaths per 100 000. In a Comment to this article, CDDEP’s director, Ramanan Laxminaryan, emphasizes that the overlooked AMR pandemic is fueled by the excessive and inappropriate use of antibiotics co-existing with the problem of insufficient access. According to Dr. Laxminaryan, significant gains can be made by investments to prevent infections in the first place, using existing antibiotics appropriately, and bringing new antibiotics to market [The Lancet].
Pfizer boosters reduce COVID-19 incidence in fully vaccinated Israeli healthcare workers. A prospective cohort study that explored the effectiveness of booster administration in 1928 younger individuals and healthcare workers (aged 36-52) showed that a third dose of the Pfizer vaccine significantly lowered the rate of SARS-CoV-2 infection in the short term. Over a median 39-day follow-up, SARS-CoV-2 infection incidence was 116 per 100,000 person-days among participants that had received two doses compared to 12.8 per 100,000 among booster immunized participants. [JAMA]
The threat of AMR needs to be addressed alongside other pandemic threats. As international organizations work towards developing a mechanism to ensure a coherent and unified pandemic response, experts emphasize the importance of developing a legal framework for addressing AMR alongside other pandemic threats. Both pandemic and AMR prevention require global cooperation across multiple sectors, equitable resource allocation, effective surveillance and enforcement, and improved legal frameworks to support accountability. In addition to scaling up investments in research and development, human resources, infection prevention measures, countries must also be prepared to assist each other, share data samples and sequences, pool procurement for essential goods, and conduct global risk assessments. [Journal of Law, Medicine & Ethics]
A new antimicrobial phenylpropanol was found to inhibit pathogenic gram-negative bacteria. A chemical investigation of the leaves of Tabernaemontana inconspicua Stapf. led to the isolation of the new phenylpropanol derivative (irisdichototin G) along with nine other known compounds. Irisdichototin G, 10-hydroxycoronaridine, and vobasine were found to have significant antimicrobial effects against Haemophilus influenzae. Irisdichototin G and vobasine also showed significant antimicrobial effects against Pseudomonas aeruginosa, as did 10-hydroxycoronaridine against Klebsiella pneumoniae. [Antibiotics]
Antivirals and monoclonal antibodies are the COVID-19 therapeutics of the Omicron era. In a recent Viewpoint, researchers from the United States summarize currently available therapeutics for non-hospitalized patients in the context of the Omicron variant. Nirmatrelvir-ritonavir is the preferred treatment due to its efficacy, with FDA Emergency Use Authorization for mild-to-moderate COVID-19 in high-risk adults and children (12+). However, nirmatrelvir-ritonavir can have serious drug interactions, making the anti-spike monoclonal antibody sotorvimab the next preferred option. Remdesivir is FDA-approved for treatment of hospitalized COVID-19 patients, but is also used off-label for high-risk non-hospitalized patients. Finally, molnupiravir has been granted FDA Emergency Use Authorization when all other options are not appropriate, but this therapeutic cannot be used in children or pregnant women. [JAMA]
Oral antivirals molnupiravir and Paxlovid have both been granted FDA Emergency Use Authorization. Molnupiravir promotes errors in the replicating SARS-CoV-2 virus until it can no longer survive, while Paxlovid blocks a protease involved in viral replication. Clinical trials for these drugs have looked at efficacy in unvaccinated individuals at high risk. Their effectiveness on vaccinated populations is not yet known, though new trials will assess this and their ability to prevent transmission. Regardless, there are concerns as treatment effectiveness is based on rapid response, which can be problematic for low- and middle-income countries with high proportions of unvaccinated individuals and limited diagnostics. [The Lancet Respiratory Medicine]
COVID-19 has prompted hospitals to refine best practices and improve management of oxygen use. Many countries experienced medical oxygen shortages in 2021, and some areas are already preparing for similar issues in the face of COVID-19, influenza, and respiratory syncytial virus cases. High-volume oxygen is often required for both critically ill and COVID-19 patients. However, logistics issues, supply chain limitations, and hospital setups limit stockpiling surplus. Redesigning or reconfiguring systems, reevaluating oxygen delivery guidelines, determining supply needs in advance, establishing conservation strategies, and strengthening delivery systems are needed to resolve this long-term challenge. [JAMA]
SARS-CoV-2 has overcome barriers that prevent the success of most pathogens. An epidemiological phylogenomic analysis explored the diversity of SARS-CoV-2 genomes to evaluate the distribution, relationships, and mutations of viral lineages in zoonotic and abiotic niches. 128 lineages were identified across 16 sources, with 30.7% Delta, 12.9% Alpha, and 12.7% B.1.1.298 variant representations, while SARS-CoV-2 reference strain Wuhan-01 was linked to a bat viral cluster. As host switching nurtures mutations, genomic surveillance should be used to monitor variant routes and respond to novel variants of concern. [One Health]
Azithromycin mass drug administration may increase macrolide resistance. A cluster-randomized trial in 30 communities in Malawi’s Mangochi District assessed if macrolide resistance is associated with azithromycin mass drug administration. Either 20 mg/kg azithromycin or a placebo was biannually administered to 1-59 month-old children between 2015-2017. At baseline, over 85% of both groups carried Streptococcus pneumoniae, with 28% resistance to macrolides. At 12 months, macrolide resistance increased to 36.9% vs. 21.6% in azithromycin and placebo groups, respectively. At 24 months, respective values were 43.9% vs. 32.8%, showing significantly increased resistance in the azithromycin group. [The Lancet Microbe]
Short but non-trivial quarantines can be as effective as travel bans during the COVID-19 pandemic. In-country transmission without travel restrictions was compared to transmission during a travel ban to identify quarantine and testing strategies that do not increase case burden. A model considering country-specific prevalence, daily incidence, vaccination coverage, travel flow, immunity, and age demographics was developed for 26 European countries. Nearly half of origin-destination pairs did not require quarantine or testing to prevent transmission increases. For the majority, testing without quarantine sufficed, and for the majority of pairs requiring controls, a short quarantine with testing could be as effective as a complete travel ban. [The Lancet Regional Health Europe]
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