Transplant patients who receive a heart from a COVID-19–infected donor may be at greater risk for death at 6 months and 1 year, finds a study published yesterday in the Journal of the American College of Cardiology.

Researchers from Montefiore Medical Center and the Albert Einstein College of Medicine identified 27,862 donors in the United Network for Organ Sharing who underwent COVID-19 testing and had data on organ disposition from May 2020 to June 2022. Donors were tested multiple times before procurement.

Donors were considered to have COVID-19 if they tested positive during hospitalization and then were subclassified as having active infection if they tested positive within 2 days of organ procurement or having recently resolved COVID-19 if they tested positive and then negative before procurement.

There is no clear consensus on the evaluation and use of COVID-19 donor hearts for transplant, the authors said.

Double the risk of death at 1 year

Of the 1,445 COVID-19 donors, 1,017 had active infections, and 428 had recently resolved cases. A total of 309 heart transplants used organs from COVID-19 donors, and 239 (150 with active infections and 89 with recently resolved cases) met the study criteria. Relative to uninfected donors, those with COVID-19 were younger, and about 80% were male.

Recipients of organs from donors with active COVID-19 infections had a higher death rate than recipients of hearts from uninfected donors at 6 months (7% vs 13.8%; hazard ratio [HR], 1.74; 95% confidence interval [CI] 1.02 to 2.96; P = 0.043) and 1 year (23.2% vs 9.2%; HR, 1.98; 95% CI, 1.22 to 3.22; P = 0.006), while recipients of organs from uninfected and recently resolved donors had similar death rates at 6 months (7% vs 8.5%) and 1 year (9.2% vs 13.6%, respectively).

These early trends should be concerning enough.

The researchers noted that SARS-CoV-2 can cause endothelial (cell layer lining blood vessels) dysfunction and heart damage that may not be detected before transplant.

"These early trends should be concerning enough such that heart transplantation centers need to thoroughly evaluate and continue to weigh the risks/benefits of using hearts from active COVID-19 donors," lead author Shivank Madan, MD, MHA, said in an American College of Cardiology news release.

Researchers with Johns Hopkins University School of Medicine reported yesterday that they identified what they believe is the first clinical case in the United States of a patient with an infection showing resistance to all available beta-lactam antibiotic regimens.

In a case report published in Open Forum Infectious Diseases, the researchers said the 66-year-old man had traveled to India to receive a kidney transplant in January 2022 and was treated at Johns Hopkins Health System for cystitis (bladder inflammation) several time from June to September 2022. The man then developed pyelonephritis (kidney infection) caused by New Delhi metallo-beta-lactamase (NDM)-producing Escherichia coli.

Although antimicrobial susceptibility testing results indicated resistance to both cefiderocol and ceftazidime-avibactam plus aztreonam (CZA-ATM)—the preferred treatment regimens for NDM-producing infections—he was continued on CZA-ATM and experienced a relapse 3 weeks later.

Further antimicrobial susceptibility testing indicated resistance to all beta-lactams. Whole-genome sequencing (WGS) of E coli isolates collected from the patient after his kidney transplant and during treatment for the infection showed they belonged to sequence type (ST)167, which has been recognized as an international high-risk clone. The ST contained a single copy of the blaNDM-5 gene, along with genes conferring resistance to penicillins, early-generation cephalosporins, aminoglycosides, trimethoprim, sulfamethoxazole, and macrolides.

The combination of resistance and virulence makes them ripe for global dissemination.

WGS also revealed a mutation in the penicillin binding protein 3, mutant CirA proteins, and expression of the blaCMY gene—a combination the study authors say almost ensures resistance to cefiderocol and CZA-ATM. They believe the patient was likely colonized with the NDM-producing E coli while in India.

"Regardless of the likely culprits of the pan-β-lactam resistance observed, this case is worrisome given that E. coli ST167 clinical isolates harboring blaNDM-5 genes are increasingly being recognized as an international high-risk clone," they wrote. "E. coli ST167 have been associated with unique virulence factors (e.g., novel capsular synthesis gene clusters); the combination of resistance and virulence makes them ripe for global dissemination."

The TB Alliance announced yesterday that it will receive up to $3.9 million in funding from the Cystic Fibrosis Foundation to investigate a compound with the potential to treat nontuberculosis mycobacteria (NTM) infections.

The funding will be used to conduct preclinical testing on a novel oxazolidinone inhibitor that was identified by researchers with the TB Alliance and Johns Hopkins University in 2020 as having the potential to treat two types of NTM, Mycobacterium abscessus and Mycobacterium avium complex. The two species cause the vast majority of NTM lung infections in people with cystic fibrosis.

Researchers will be looking to see whether the synthetic antibiotic is more effective against NTM infections than linezolid, the antibiotic currently used to treat M abscessus infections.

Identifying this new compound will allow our researchers to potentially develop a new, improved treatment for NTM infections.

"At TB Alliance, we are focused on discovering and developing novel treatments for tuberculosis. Through this work, we found several possible compounds that had the potential to treat NTMs, which are related to the TB bacteria," Nader Fotouhi, PhD, senior vice president and chief scientific officer at TB Alliance, said in a press release. "Identifying this new compound will allow our researchers to potentially develop a new, improved treatment for NTM infections that may help people with cystic fibrosis."