A study conducted at two Rhode Island hospitals found that exposure to opioids was associated with a nearly four-fold risk in vancomycin-resistant Enterococci (VRE) colonization, researchers reported this week in the American Journal of Infection Control.

The matched case-control study, led by researchers at Brown University, aimed to identify specific non-antimicrobial medications associated with VRE rectal colonization. While antimicrobial exposure is one of the main factors contributing to the emergence and spread of VRE and other multidrug-resistant organisms (MDRO), a recent meta-analysis found that more than 16% of patients who acquired an MDRO had no antimicrobial exposure. Cases and controls were defined as patients with and without VRE rectal colonization at hospital admission, respectively, none of whom had received antimicrobials in the prior 12 months.

Opioid exposure only significant risk factor

Among 59,986 admissions to the two hospitals from April 15 to November 12, 2019, 2,919 patients (4.8%) were identified with VRE colonization on admission. Among these patients, 27 were confirmed as having no previous antimicrobial exposure, and they were matched to 63 control patients.

Multivariate analysis found that of the 17 different classes of medications patients had been exposed to, opioids (oxycodone) were the only significant and independent risk factor associated with VRE colonization (adjusted odds ratio, 3.8; 95% confidence interval, 1.4 to 10.8).

"This is a novel finding as previous studies of factors associated with VRE colonization have not focused on non-antimicrobial medications," the study authors wrote.

The authors explain that opioids have been shown to induce gut microbiome dysbiosis, which can reduce microbial diversity and lead to an increased risk of MDRO colonization in the gut. Although more research is needed to elucidate the mechanisms behind the association, they say there may be a need to implement infection prevention strategies aimed at limiting the acquisition and spread of MDROs among opioid users.

This is a novel finding as previous studies of factors associated with VRE colonization have not focused on non-antimicrobial medications.

Two stroke centers in Canada and the United States saw a significant reduction in monthly hospital presentations and workflow speeds in the first two waves of the COVID-19 pandemic, finds a study published today in Scientific Reports.

Researchers at Harvard Medical School and the University of Calgary analyzed changes in stroke rates, hospital systems of care, and treatment times at two comprehensive stroke centers in Boston and Calgary before and during the pandemic (January 2018 to May 2021). The study period was divided into period 1 (pandemic wave 1), period 2 (lull), and period 3 (wave 2).

No significant rise in hospital stroke deaths

Of the 3,816 patients seen at the Calgary clinic, 69.3% had an ischemic stroke before the pandemic, and 30.7% had one during the pandemic; 80.0% were hospitalized. At the Boston center, 2,400 patients had an ischemic stroke, 66.1% of them prepandemic and 33.9% amid the pandemic; only 1% had the same admit and release date.

During wave 1, monthly stroke counts fell significantly, and both centers noted reductions in therapies to restore blood flow, which gradually rose but not to prepandemic levels before dropping again during wave 2.

Strategies must be taken to continue to motivate patients to seek care even during pandemic and stroke protocols should accommodate measures to mitigate inefficiencies.

Both centers had in-hospital workflow delays that resulted in slower stroke diagnosis and treatment during waves 1 and 2 and the lull period, likely due to hospital SARS-CoV-2 infection-prevention mandates (eg, donning personal protective equipment, additional cleaning processes, relocation of services). There were no significant changes in rates of in-hospital deaths due to stroke.

The study authors said that physical-distancing messages could have inadvertently led patients with emergent conditions such as strokes to avoid hospitals. Lockdowns and disruptions to services and support networks for older people and those with disabilities may also have been barriers to seeking care for emergencies.

"Strategies must be taken to continue to motivate patients to seek care even during pandemic and stroke protocols should accommodate measures to mitigate inefficiencies," they concluded.

Pennsylvania-based Venatorx Pharmaceuticals announced yesterday that it has received a $167 million contract from the Biomedical Advanced Research and Development Authority (BARDA) to develop a novel oral antibiotic for complicated urinary tract infections (cUTIs).

The BARDA award will support development of ceftibuten-ledaborbactam etzadroxil, which combines a cephalosporin antibiotic with a novel, broad-spectrum boronic acid beta-lactamase inhibitor. Venatorx says the combination may offer a new oral treatment option for outpatient therapy to treat cUTIs and other serious bacterial infections caused by multidrug-resistant Enterobacterales.

An estimated 2.8 million cUTI cases are diagnosed annually in the United States, and cUTIs caused by drug-resistant bacteria are on the rise.

"Currently, there are no approved oral antibiotics that are effective in the treatment of drug-resistant gram-negative bacterial infections to help address increasing drug-resistant bacterial infections globally," Venatorx President and CEO Christopher Burns, PhD, said in a company press release. "We believe that oral ceftibuten-ledaborbactam etzadroxil could play an important role in treating drug-resistant gram-negative infections, preventing unnecessary hospitalizations, and saving lives."

Ceftibuten-ledaborbactam etzadroxil has been granted Qualified Infectious Disease Product and Fast Track designation by the US Food and Drug Administration (FDA) and has recently completed phase 1 clinical studies. The drug will advance directly to phase 3 trials under the BARDA contract.

NDA approved for ceftobiprole

In other antibiotic-development news, Swiss biopharmaceutical company Basilea Pharmaceutica announced last week that the FDA has approved its New Drug Application (NDA) for ceftobiprole. The company is seeking approval for treating patients with Staphylococcus aureus bacteremia (SAB), acute bacterial skin and skin structure infections, and community acquired bacterial pneumonia.

"We are pleased with the FDA's acceptance of our New Drug Application, which is another important step towards bringing ceftobiprole to patients with severe bacterial infections in the US, as there is a high medical need for new antibiotic treatment options, especially in complicated SAB," Basilea Chief Medical Officer Marc Engelhardt, MD, said in a press release.

Following the detection of two recent human H5N1 avian flu infections in Cambodia, genetic sequencing led by scientists at the Pasteur Institute in Phnom Penh revealed that the virus belongs to the 2.3.2.1c clade, similar to viruses that have been circulating in the region over the past decade. Lab scientists announced their findings today on Twitter.

Earlier this week, Cambodia reported two human H5N1 cases, including a fatal infection in a 2-year-old girl from Prey Veng province and an illness in a 50-year-old man from neighboring Svay Rieng province. In both instances, poultry deaths were reported near their homes.

In February, Cambodia reported two similar H5N1 cases, which also involved the earlier clade. That clade is different than the 2.3.4.4b clade circulating widely in wild birds and poultry, with sporadic spillovers to mammals and humans who had contact with sick poultry or contaminated environments.

• Florida Health has recorded 15 more locally acquired dengue cases, raising the season's total to 53. Cases have been concentrated in Miami-Dade County (47 cases) and Broward County (3 cases), with single cases reported in Palm Beach, Hardee, and Polk counties.
• Today, the World Health Organization (WHO) announced that European groups and the Gates Foundation are putting together a finance package of 1.1 billion Euros to support the polio vaccination of 370 million children, with the goal of disease eradication. “We are about to wipe polio off the face of the Earth. The European Commission, the EIB [European Investment Bank] and the Bill & Melinda Gates Foundation are partnering to get through the final stretch,” said European Commission President Ursula von der Leyen in a press release. Half of the funds will be made available to the Global Polio Eradication Initiative, which will oversee the vaccination of 370 million children. The second half of the funding will be used to expand vaccine-delivery innovation for low- and middle-income countries
• John-Arne Rottingen, a Norwegian medical scientist, is the new CEO of the Wellcome Trust, one of the world’s largest private funders of medical research. Rottingen is replacing Jeremy Farrar, who now serves as the WHO’s chief scientist. Røttingen previously worked as the founding chief executive officer of the Coalition for Epidemic Preparedness Innovation (CEPI) and currently is Norway’s ambassador for global health.