A study conducted in a New York City health system identified several patients infected with dual-carbapenemase–producing organisms (DCPOs), researchers reported late last week in JAC-Antimicrobial Resistance.

In the study, researchers at Icahn School of Medicine at Mount Sinai used rapid molecular testing to identify 26 DCPO isolates from 13 patients treated at Mount Sinai Hospital from 2018 through 2021. Twenty-four of the isolates were from the Enterobacterales order (22 Klebsiella pneumoniae, 1 Escherichia coli, and 1 Enterobacter isolate) and 2 were Pseudomonas aeruginosa. The most common carbapenemase combination was bla_NDM/bla_OXA-48-like, which was found in 16 isolates, and whole-genome sequencing revealed that the DCPOs were located on distinct plasmids.

All 26 isolates were resistant to penicillins, cephalosporins, ampicillin/sulbactam, and piperacillin/tazobactam, and 7 were non-susceptible to all antibiotics tested.

Previous hospitalization, antibiotic exposure common

Analysis of patient data showed that 11 of the patients had been hospitalized in the prior year (7 in the intensive care unit) and had received antibiotics within the last month, 7 were from foreign countries, and all had at least one underlying condition. High blood pressure, kidney disease, and diabetes were the most frequently seen comorbidities. Six of the patients died, with two of the deaths directly attributed to the DCPO infection.

The study authors say the findings are concerning, because DCPOs further compromise the already limited treatment options for carbapenemase-producing organisms and could threaten the utility of newer antibiotics. Furthermore, their location on plasmids could facilitate horizontal gene transfer and lead to multispecies dissemination of DCPOs.

"Infectious diseases physicians should be aware of this threat, as our study shows high mortality in patients infected or colonized with DCPOs," they wrote. "Further research into appropriate management of infections caused by DCPOs is needed."

Invivyd, a biotechnology company based in Massachusetts, today announced that it has submitted a request with the US Food and Drug Administration (FDA) for an emergency use authorization (EUA) for its monoclonal antibody to prevent COVID-19.

The drug, called VYD222, is a broadly neutralizing, half-life extended monoclonal antibody for pre-exposure use in immunocompromised adults and adolescents. In a statement, the company said the EUA filing is supported by a phase 3 trial and ongoing in vitro studies to assess its activity against SARS-CoV-2 variants such as JN.1. The clinical trials have been testing a 4,500-milligram dose given by intravenous infusion.

No approved monoclonal antibodies

Currently, there are no monoclonal antibodies authorized or approved by the FDA. In January 2023, the FDA pulled its EUA for an earlier monoclonal antibody preventive called Evusheld after data suggested that it was unlikely to be active against certain SARS-CoV-2 variants.

Dave Hering, MBA, Invivyd's chief executive officer, said, "We believe that the demonstrated durability of VYD222 is reflective of our strategy to select antibody candidates that target conserved epitopes to achieve our stated goal of keeping pace with viral evolution." He added that many immunocompromised people don't achieve full benefit from COVID-19 vaccines, and pre-exposure treatments can provide an important new prevention option.

If the drug is authorized, the company hopes to make VYD222 rapidly available soon afterward.

Yesterday in the Journal of Infectious Diseases, researchers described a 2016 mpox outbreak that affected 20 captive chimpanzees at a sanctuary in central Cameroon.

At the time of the clade 1 outbreak in August through October, the sanctuary housed about 300 chimpanzees, gorillas, and monkeys in 18 groups. Mpox affected 20 of 23 adult and younger chimpanzees (14 male and 9 female) in one group. No animals had been moved into or out of the group in the previous 6 months.

Better monitoring, control measures needed

From August to September, 3 chimpanzees were confirmed to have mpox, and 17 had probable cases, for an 87% attack rate. The most common signs were rash (90%), lethargy (85%), and facial or peri-laryngeal swelling (70%). Two of the animals died, for a case-fatality rate of 10%. The rest of the chimpanzees recovered and were considered no longer infectious by late October.

Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures.

After the first mpox case was detected, the sanctuary reported it to the Cameroon Epidemiological Network for Animal Diseases, and the onsite veterinarian documented daily signs, dates of onset and death, movements between cages, and treatment in the affected group. Nose-throat and rectal swabs were collected from chimpanzees who died or were immobilized for treatment.

For the 17 unaffected groups, caretakers visually inspected each animal each day for mpox signs, behavioral changes, and night shelter use, and a veterinarian did the same at least twice a week. Animals were quarantined if they showed mpox signs or had direct or indirect contact with the affected group.

Animal caretakers were monitored daily for mpox signs for 17 days; none developed a characteristic rash or fever.

"There is a need for increased awareness and a One Health approach to preparation for outbreaks in wildlife rescue centers in primate range states were MPXV [mpox virus] occurs," the researchers wrote. "Control measures should include quarantining affected animals, limiting human contacts, surveillance of humans and animals, use of personal protective equipment, and regular decontamination of enclosures."