Carbapenems commonly used in Enterobacterales infections despite guidance
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Key takeaways:
- Carbapenems were prescribed as targeted therapy in 58.3% of all infections.
- Highlighting patient populations that receive carbapenems may help with efforts to reduce exposure.
Carbapenems were commonly prescribed as targeted therapy for extended-spectrum cephalosporin-resistant Enterobacterales infections despite significant changes in updated guidance, data show.
“Following the publication of the MERINO trial there was a movement towards using carbapenems for treatment of all extended spectrum beta lactamase (ESBL) producing Enterobacterales infections,” Morgan K. Walker, MD, a fellow in the critical care medicine department at the NIH Clinical Center, told Healio. “Since that time, some evidence suggests that carbapenem-sparing therapies may be reasonable alternative options for treatment of non-severe ESBL-E infections.”
With this evidence came guidance from multiple agencies recommending specific usage of carbapenems.
The 2020 version of the Infectious Diseases Society of America expert practice guidance for antibiotic-resistant Gram-negative infections recommended “liberal use” of carbapenems for complicated UTIs and
pyelonephritis and all ESBL-producing Enterobacterales infections outside of the urinary tract, “irrespective of illness severity,” Walker and colleagues wrote.
The 2021 European Society for Clinical Microbiology and Infectious Diseases guidelines then recommended limiting the use of carbapenems to “severe manifestations” of extended-spectrum cephalosporin-resistant (ECR) Enterobacterales infections, including septic shock or bacteremia.
Updated IDSA recommendations from 2023 favored carbapenem stewardship and removed carbapenems from the list of first-line options for complicated UTIs and pyelonephritis caused by ESBL-producing Enterobacterales.
To better understand the prevailing antibiotic therapy for these infections, and to assess if the updated guidance from IDSA impacted prescribing patterns in the U.S., Walker and colleagues conducted a retrospective cohort study, assessing all adults admitted to hospital with ECR Enterobacterales infections in the PINC AI database.
The researchers assessed antibiotic regimens during empirical and targeted treatment periods and by infection severity and site. They also determined the likelihood of receiving targeted carbapenems over time, as well as before or after initial release of the IDSA guidance on Sept 8, 2020.
The researchers identified 30,041 inpatient encounters with extended-spectrum cephalosporin-resistant (ECR) Enterobacterales infections at 168 U.S. hospitals between Jan. 1, 2018, and Dec. 31, 2021. Among these patients, 5,324 (17.7%) received carbapenems empirically; however, many received them as targeted treatment (17,518; 58.3%), including subgroups of patients without septic shock (3,031; 45.6%) and patients with UTIs without septic shock (1,845; 46.8%).
Additionally, carbapenems were the main choice to treat ECR Enterobacterales infections over time (adjusted OR = 1; 95% CI, 1-1), with no additional immediate change (aOR = 1.07; 95% CI, 0.95-1.2) or sustained change (aOR = 0.99; 95% CI, 0.98-1) after the updated IDSA guidance release.
“By understanding the prevailing antibiotic treatment of these infections and the impact of current guidance recommendations, we were able to highlight a population where focused efforts may reduce carbapenem exposure and, consequently, carbapenem selective pressure,” Walker told Healio.
Erika J. Ernst, PharmD, associate professor of pharmacy practice and science at the University of Iowa College of Pharmacy, wrote in an accompanying commentary that based on these findings, the study “perhaps unsurprisingly” did not show any impact from the IDSA guidance on the rate of carbapenem use.
“No immediate or sustained effects were observed, nor were there effects when looking at subgroups of sepsis, no sepsis, or genitourinary infections without sepsis, in sensitivity analyses that included complete-case records only or a washout period, and in a traditional interrupted time series analysis,” she wrote. “Perhaps the level of evidence was not high enough or the disparate guidance was too confusing to overcome the influence of the widely disseminated MERINO trial.”
She added that the move away from guidelines towards more rapidly available guidance documents is a step in the right direction but warned that rapidly changing guidance could lead to “uncertainty and inertia.”
References:
- Ernst EJ. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00231-7.
- Walker MK, et al. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00149-X.
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Walker MK, et al. Lancet Infect Dis. 2024;doi:10.1016/S1473-3099(24)00149-X.
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