Stewardship / Resistance Scan for Jun 09, 2022

News brief

PAHO issues alert on extremely drug-resistant Shigella

The Pan American Health Organization (PAHO) this week issued an alert on the potential emergence and spread of extremely drug-resistant (XDR) Shigella sonnei in Latin America and the Caribbean.

Although to date cases of shigellosis caused by S sonnei have been reported only in countries with high surveillance capacity and high water, sanitation, and hygiene standards, the alert notes that cases of gastrointestinal infection caused by XDR S sonnei in men who have sex with men (MSM) have been rising in the United Kingdom and several other European countries. While shigellosis—one of the leading causes of severe infectious disease worldwide—is mainly caused by consumption of contaminated food and water, it can be transmitted through oral and anal sex and is considered a sexually transmitted disease.

Because millions of people in the Americas still lack access to clean drinking water and safe facilities for the disposal and elimination of feces, PAHO is concerned that if XDR S sonnei is introduced into the region in travelers returning from endemic areas, including MSM, there will be an increased risk of a major outbreak of diarrheal diseases that could be lethal in the main risk groups, including children under 5 years.

"Also of concern is the possible contribution of S. sonnei XDR to the spread of antibiotic resistance in the community through horizontal transfer of mobile genetic elements such as plasmids to other bacterial species," PAHO said.

Given this risk, PAHO is recommending that national authorities in the region strengthen surveillance and epidemiologic investigation of XDR S sonnei, strengthen the ability of clinical labs to identify and monitor resistance in S sonnei, continue efforts to provide access to safe water and adequate sanitation, boost infection prevention and control measures in healthcare settings, and work to prevent and minimize sexual transmission of the pathogen.
Jun 6 PAHO epidemiologic alert

Phage therapy shows promise in patients with non-TB Mycobacterium

Compassionate use of bacteriophage therapy in a small cohort of patients with antibiotic-resistant non-tuberculosis Mycobacterium (NTM) infections was well-tolerated and produced favorable responses in more than half, an international team of researchers reported today in Clinical Infectious Diseases.

For the study, a team led by researchers from the University of Pittsburgh and the University of California San Diego screened 200 isolates from patients with antibiotic-refractory NTM infections for susceptibility to bacteriophages. NTM infections, particularly those caused by Mycobacterium abscessus, are increasingly common among patients with cystic fibrosis and chronic bronchiectatic lung diseases and have become challenging to treat because of intrinsic antibiotic resistance. Based on two previous case reports of successful compassionate use of bacteriophages in NTM patients, the researcher wanted to further explore the potential.

Screening identified lytic phages for 55 isolates, and 20 patients who met the eligibility criteria were selected to receive personalized adjunctive phage therapy intravenously or by aerosolization. In 11 cases, only a single phage candidate was identified; in others, two or more phages were combined into a cocktail. The patients were monitored for adverse reactions, clinical and microbiologic responses, the emergence of phage resistance, and phage neutralization in serum, sputum, or bronchoalveolar lavage fluid.

No adverse reactions attributed to therapy were seen in any patient, and favorable clinical or microbiological responses were observed in 11 patients, with infections largely resolved in 5. Some patients, however, saw little clinical benefit. Neutralizing antibodies were identified in serum after initiation of phage delivery intravenously in 8 patients, potentially contributing to lack of treatment response in 4, but were not consistently associated with unfavorable responses in others. No phage resistance was observed in any of the 11 patients who received a single phage.

The study authors say further research into optimal routes of administration, dosage, pharmacodynamics, and tissue penetration is needed.

"This series of 20 patients treated with phages on a compassionate-use basis provides support for further evaluation of phages for treatment of mycobacterial infections," they wrote. "Although phage treatment of mycobacterial infections shows promise, this cohort illustrates some key limitations and lessons."
Jun 9 Clin Infect Dis abstract

News Scan for Jun 09, 2022

News brief

Risk of COVID-related syndrome lower in kids after breakthrough Omicron

The risk of COVID-19–related multisystem inflammatory system in children (MIS-C) was significantly lower among vaccinated versus unvaccinated Danish children after infection with the Omicron variant rather than with previous strains, according to a research letter published yesterday in JAMA Pediatrics.

A team led by Aarhus University researchers used Danish COVID-19 surveillance registries to prospectively study 0- to 17-year-old patients diagnosed as having MIS-C at all of the country's 18 Danish pediatric healthcare units from Jan 1 to Mar 15, 2022. They were infected from Jan 1 to Feb 1, 2022, when Omicron made up 95% of variants in that country.

Of the 583,618 children and adolescents estimated to have had COVID-19, 267,086 were vaccinated. Among those with COVID, 1 vaccinated and 11 unvaccinated MIS-C patients were identified.

Amid Omicron, the risk of MIS-C was 89% lower in vaccinated versus unvaccinated patients (risk ratio [RR], 0.11; 95% confidence interval [CI], 0.01 to 0.83). The risk was 88% lower in unvaccinated patients during Omicron than during the Delta wave (RR, 0.12; 95% CI, 0.06 to 0.23) and 86% lower than during the wild-type virus wave (RR, 0.14; 95% CI, 0.07 to 0.29). There was no difference in MIS-C signs and symptoms between Omicron and previous variants.

The authors said the findings may be attributed to Omicron's reduced ability to cause hyperinflammation, because it is less likely to trigger the immune system.

"The lower risk could also partly be explained by a reduced risk after reinfection, although only 6% of our included infected individuals had confirmed reinfection, and such a reduced risk after reinfection has not yet been reported," they wrote, acknowledging that the study was limited by the few MIS-C patients.

The lower risk of MIS-C after Omicron reinfection in vaccinated patients may also be due to the high effectiveness of the COVID-19 vaccine, the researchers said. "This may be caused by vaccine-induced modulation of the immune system, rendering it less prone to cause hyperinflammation after SARS-CoV-2 infection," they wrote.
Jun 8 JAMA Pediatr research letter

Avian flu turns up in Washington, DC, and Arizona

Marking the first highly pathogenic avian flu detection in the nation's capital, the National Park Service (NPS) yesterday said the virus has been detected in mallard ducklings in the Lincoln Memorial's reflecting pool. Also, Arizona reported its first detection in wild birds, cormorants at a park in Scottsdale.

The NPS said avian flu had been detected earlier in domestic and wild birds in states surrounding Washington, DC—Delaware, Maryland, and Virginia. It said though the virus poses a low risk to humans, visitors should avoid handling live or dead birds or coming in contact with their droppings.

In Arizona, highly pathogenic H5N1 was found in three nestling cormorants found dead in Eldorado Park in Scottsdale, according to a statement from the Arizona Game and Fish Department. So far, no outbreaks have been reported in Arizona poultry.

In related developments, federal officials today reported four more outbreaks in poultry in three states, all involving backyard flocks. According to updates from the US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS), Indiana reported two outbreaks in Allen County, Oregon reported an outbreak in Polk County, and Washington reported another in King County.

Though outbreaks in poultry have slowed, the virus continues to be reported broadly across the United States. APHIS continues to report dozens of H5N1 detections in wild birds each week, with 1,422 reported since the middle of January.
Jun 8 NPS statement
Jun 8 Arizona Game and Fish statement
USDA APHIS poultry outbreak updates

Connecticut reports fatal Powassan virus infection

Connecticut this week reported its second Powassan virus case of the year, involving a patient from New London County in the southeastern corner of the state who died from her infection.

In a statement, the Connecticut Department of Health (CDH) said the woman in her 90s and became ill in early May, about 2 weeks after she was bitten by a tick. Over the next 2 weeks, her condition worsened, and she died on May 17. Lab tests conducted by the Centers for Disease Control and Prevention (CDC) confirmed antibodies to Powassan virus.

Connecticut's first case of the year was in a man in his 50s from Windham County in the state's northeastern corner who was sick in late March after a tick bite. He was hospitalized with neurologic symptoms but was discharged and recovered at home.

From 2017 through 2021, Connecticut reported 12 Powassan virus cases, 2 of them fatal. Last year, the state reported 3 of those cases.

The disease, mainly spread by black-legged (deer) ticks, causes symptoms that range from headache to encephalitis. There is no treatment. Most cases are reported from Great Lakes and northeastern states. The CDC typically receives reports regarding a dozen or more Powassan virus cases affecting the nervous system each year, with the most—39 cases—in 2019.
Jun 7 CDH statement