News Scan for Sep 15, 2021

News brief

NDM-producing Enterobacterales levels rising in Switzerland

Researchers in Switzerland have identified an increase in New Delhi metallo-beta-lactamase (NDM)–producing Enterobacterales, according to a report published today in Emerging Infectious Diseases.

Of the 532 carbapenemase-producing Enterobacterales (CPE) samples obtained from Swiss hospitals and clinics in 2019 and 2020, 141 were confirmed to be NDM-positive—accounting for more than 25% of all CPE submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA). NDM enzymes are capable of conferring resistance to nearly all beta-lactam antibiotics, including carbapenems, and treatment options for infections caused by NDM-producing Enterobacterales are limited, as they frequently harbor additional resistance genes.

Most of the NDM-positive isolates were either Klebsiella pneumoniae (59 of 141) or Escherichia coli (52 of 141), and more than 50% were obtained from screening swab samples. Among the 108 isolates that were sequenced, NDM-1 was the most prevalent, occurring in 56 isolates, mostly K pneumoniae (34 of 56). NDM-5 was the next most common, occurring in 40 of 49 E coli isolates, and other variants included NDM-4 and NDM-7. Fourteen of the isolates co-produced a second carbapenemase, predominantly an OXA-48-like enzyme, and almost one third of the isolates produced a 16S rRNSA methylase conferring high-level resistance to aminoglycosides.

Further molecular analysis found that the E coli and K pneumoniae isolates harbored multiple plasmids and belonged to sequence types and clonal complexes that have been identified in hospital outbreaks in other parts of the world. The authors of the study suggest these successful lineages are likely responsible for the observed increase in NDM-producing Enterobacterales.

"This 2-year study gives a snapshot of the epidemiology of NDM producers in Switzerland and illustrates how the use of [whole-genome sequencing] is both an essential and informative tool for surveillance and for monitoring emerging resistance," the study authors write. "Our findings underpin the importance of the surveillance of NDM-producing bacteria and particularly the monitoring of successful clonal lineages and plasmids."
Sep 15 Emerg Infect Dis study

Global flu stays low, though H3N2 rising in South Asia

In a global flu update that covers the last half of August, the World Health Organization (WHO) this week said overall activity remained very low in both hemispheres, though levels continue to increase in India and Nepal. The agency included its usual caveat that flu activity and detection are likely affected by COVID-19 measures and the pandemic's impacts on surveillance.

Flu circulation in India and Nepal is dominated by H3N2. Elsewhere, locations in the Americas, including the Caribbean, Central America, and Mexico, reported sporadic influenza B cases, and parts of Africa continue to report sporadic flu cases.

Of the few respiratory specimens that were positive for flu during the end of August, 62.2% were influenza A, and of the subtyped influenza A viruses, 93.3% were H3N2. Of characterized influenza B viruses, all but two belonged to the Victoria lineage.
Sep 13 WHO global flu update

COVID-19 Scan for Sep 15, 2021

News brief

Face coverings offer modest source control for COVID-19, study finds

Cloth or surgical facial masks reduced SARS-CoV-2 RNA 77% in exhaled coarse aerosol particles and 48% in exhaled fine aerosol particles, offering "modest" source control, according to a Clinical Infectious Diseases study yesterday. The study also found that the Alpha (B117) COVID-19 variant contained 43-fold more fine-aerosol viral RNA compared with earlier virus strains.

The study used breath samples collected using a Gesundheit II machine, which was developed by senior study author Donald Milton, MD, PhD, of the University of Maryland. The machine measures viral shedding in exhaled breaths during talking and other vocalizations. "Source control" refers to covering the mouth and nose to reduce expelled pathogens and thus the likelihood of disease transmission.

To conduct the study, Milton and colleagues had 49 COVID-19 case-patients provide paired breath samples at two visits 2 days apart, first while wearing a mask and then without. At one visit, a surgical mask was provided; at the other visit, the participants wore their own masks. Participants recited the alphabet, sang, and yelled during their visit. All cases were asymptomatic or mild at the time of study, and no one was taking antiviral medications.

Alpha variant infection was associated with a 100-fold and a 73-fold increase in coarse- and fine-aerosol RNA shedding, respectively (95% confidence intervals [CIs], 16- to 650-fold and 15- to 350-fold). Surgical masks did not outperform cloth masks, and there was an overall reduction of 77% (95% CI, 51% to 89%) coarse and 48% (95% CI, 3% to 72%) fine aerosols.

"Alpha variant infection yielded one to two orders of magnitude more viral RNA in exhaled breath when compared with earlier strains and variants not associated with increased transmissibility. Our observation of increased aerosol shedding, even after controlling for the increased amounts of viral RNA in the nose and mouth, suggests that evolutionary pressure is selecting for SARS-CoV-2 capable of more efficient aerosol generation," the authors write.

The team was also able to culture live SARS-CoV-2 from 2 of 66 fine-aerosol samples, 1 of which was the Alpha variant.

They conclude, "Loose-fitting masks provide significant but only modest source control. Therefore, until vaccination rates are very high, continued layered controls and tight-fitting masks and respirators will be necessary."
Sep 14 Clin Infect Dis study

Remdesivir did not improve COVID-19 death rate, outcomes in trial

Remdesivir treatment did not significantly affect mortality, clinical outcomes, or time to improvement in patients hospitalized with severe COVID-19, according to a study published in The Lancet Infectious Diseases yesterday.

The data included results from the DisCoVeRy trial, which the researchers say is the fifth large, randomized, controlled trial to include remdesivir thus far. The cohort was recruited from 48 sites in Europe, with 39 sites in France. Exclusion criteria included elevated liver enzymes, severe chronic kidney disease, and pregnancy.

From Mar 22, 2020, to Jan 21, 2021, 857 adults were randomly assigned to either standard of care or standard of care plus remdesivir.

By day 15, clinical outcomes were not significantly better in the intervention group (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.77 to 1.25). No significant difference was seen in 28-day mortality (OR, 0.98; 95% CI, 0.57 to 1.52) or time to improvement.

The only significant association was in a subgroup of patients without mechanical ventilation or extracorporeal membrane oxygenation (ECMO), in which those given remdesivir had a 34% (95% CI, 0.47 to 0.91) lower risk of new mechanical ventilation, ECMO, or death.

The median time from symptom onset to treatment was 9 days.

"[Time to treatment] might explain why no effect of remdesivir on viral clearance was seen in any of these studies," write Iwein Gyselinck, MD, and Wim Janssens, MD, PhD, in a related commentary, noting that the treatment may still have use in specific populations. Still, they conclude, "As findings from DisCoVeRy show an absence of effect on late clinical status and mortality, there is no reason to advocate remdesivir use outside of clinical trials."
Sep 14 Lancet Infect Dis study and commentary

Daily school COVID testing, isolation have similar efficacy, study says

Daily antigen testing of close COVID-19 contacts was shown to be comparable to 10-day isolation periods, according to a study yesterday in The Lancet.

The researchers looked at 201 English schools for ages 11 to 18 years from Apr 19 to Jun 27, 2021. About half the schools (99) were assigned to be the control group, implementing a 10-day isolation period for any student or staff member who was in close contact with a COVID-19 index patient, while close contacts in the intervention schools received COVID-19 antigen testing every weekday until five negative tests or a positive test occurred.

The prevalence of confirmed COVID-19 infections was 59.1 per 100,000 people per week in the control group and 61.8 per 100,000 people per week in the intervention group. COVID-related absences were similar as well, with the control group having 1.6% of their person-school-days marked as absent, versus 1.3% of the intervention group. Overall, 1.6% of contacts in the control group were identified as asymptomatically infected, compared with 1.5% in the intervention group.

"One might argue that, regardless of the lack of difference in the transmission outcomes, the inability to show reduction in school absence means that the intervention failed to reduce educational disruption, greatly reducing its usefulness," write Russell M. Viner, MBBS, PhD, and Archana Koirala, MBChB, DCH, MIPH, in a related commentary.

"However, the lack of a change in school absence at the 0.05 significance level probably reflects a lack of power, as the [confidence intervals] were consistent with reduced absences at a lower significance," they continued. "Moreover, daily testing regimens provide increased flexibility and choice for families and schools."

The researchers note that not all individuals who were eligible for the daily testing intervention chose to participate and that the intervention couldn't be applied in some absence-related situations (eg, household contacts were ineligible). The daily antigen tests themselves showed 53% sensitivity and 99.9% specificity rates.
Sep 14 Lancet study and commentary