Analysis of blood and urine from hospitalized patients in a large New York health system found that detection of a multidrug-resistance gene was common and associated with high mortality, researchers reported yesterday at IDWeek 2024.
The gene, blaNDM, is one of the five most prevalent carbapenemase genes found in US hospitals, which have seen a rise in carbapenemase-producing organisms (CPOs) over the last several years. The genes carried by CPOs confer resistance to carbapenems and many other classes of antibiotics, making infections caused by these organisms difficult to treat. Data from the Centers for Disease Control and Prevention suggest the blaKPC gene is the most prevalent carbapenemase gene found in CPOs in US patients.
In the retrospective study, researchers from Northwell Health, New York’s healthcare provider, analyzed blood and urine cultures that were positive for a CPO from January 2021 to December 2023, using blood culture polymerase chain reaction (PCR) results and a lateral flow immunoassay (for urine cultures) to identify carbapenemase genes. They then evaluated clinical outcomes, including mortality, length of hospital stay, and time to appropriate therapy in patients with CPOs.
“With such an urgent threat on the rise, our study really sought to provide better understanding of CPOs and how to tackle these types of infections,” study co-author Kirby An, PharmD, said in an ID Week press briefing.
Changing resistance patterns, high mortality
A total of 71 CPO-positive blood cultures and 50 CPO-positive urine cultures from 10 hospitals were included in the analysis. Most of the patients were ages 68 to 71 years, with similar baseline characteristics. Klebsiella pneumoniae was the most predominant CPO detected. Of the carbapenemase genes detected, blaNDM was found in 39% of CPOs isolated from blood and 46% isolated from urine. Other carbapenemase genes detected included blaKPC, blaOXA-48-like, and blaVIM (found only in the urine cultures).
An noted that when he and his colleagues looked at the trends over time, they found that in 2021, there was very little detection of blaNDM. But there was significant increase in blaNDM detection in blood cultures in 2022, and that trend continued in 2023. In the CPO-positive urines cultures, which were only analyzed for 2023, they found that the number of organisms carrying blaNDM and blaKPC were similar.
“This is particularly concerning because the NDM gene confers resistance to most of our antibiotics, including a majority of the newer antibiotics that have been released for the treatment of these carbapenem-resistant organisms,” he said.
Analysis of clinical outcomes showed that the overall mortality rate was 39% for bloodstream infections and 6% for urinary infections. But the presence of blaNDM in blood cultures was associated with 48% mortality. In addition, length of hospital stays in patients with CPO-positive blood cultures jumped from 14.5 days in 2021 to 24 days in 2022, when the spike in blaNDM cases began. Further analysis showed patients with blood infections carrying blaNDM had hospital stays of up to 30 days.
This is particularly concerning because the NDM gene confers resistance to most of our antibiotics, including a majority of the newer antibiotics that have been released for the treatment of these carbapenem-resistant organisms.
While the shifting trend in antibiotic-resistance mechanisms is worrisome, the researchers note that mortality for CPO-producing bloodstream infections did decline to 33% in 2023—still “really, really high,” An said—and that time to appropriate antibiotic therapy declined from around 10 hours in 2021 to around 2 hours in 2023. They attribute this in part to a better understanding of the resistance mechanisms they were dealing with, as well as a tele-antimicrobial stewardship service staffed by infectious disease pharmacists who can respond quickly to culture results and tailor the antibiotic treatment.
“There’s no one-size-fits-all treatment for CPO infections — you have to know exactly what you’re treating, all the way down to the genetics,” Aya Haghamad, PharmD, pharmacy advisor at Northwell Health and lead author of the study, said in an IDWeek press release. “Our study underscores how important it is to be able to identify carbapenemases — doing so allowed our team to improve patient outcomes and ensure appropriate prescribing of antimicrobial therapies.”
IDWeek is the joint annual meeting of the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the HIV Medicine Association, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists.
