Study: New antibiotics underprescribed for difficult-to-treat infections

Key takeaways:

• The FDA approved eight next-generation gram-negative antibiotics since 2014.
• More than one-third of 619 hospitals examined in the study never used these newer antibiotics.

BOSTON — More than 40% of patients with difficult-to-treat pathogens were prescribed older, generic agents despite the FDA approval of several new gram-negative antibiotics, findings showed.

According to Sameer S. Kadri-Rodriguez, MD, MS, a staff clinician at the NIH, and colleagues, eight next-generation gram-negative antibiotics have been approved by the FDA since 2014, which include:

• ceftolozane-tazobactam;
• ceftazidime-avibactam,
• meropenem-vaborbactam;
• plazomicin;
• eravacycline;
• imipenem-cilastatin-relebactam;
• cefiderocol; and
• sulbactam-durlobactam.

During the plenary session at the ACP Internal Medicine Meeting, Kadri-Rodriguez said he and his colleagues conducted a study to “see how clinicians use these” antibiotics.

In the retrospective cohort pharmacoepidemiologic study — which was simultaneously published in Annals of Internal Medicine — the researchers assessed the use of recently-approved gram-negative antibiotics across 619 hospitals “using a new paradigm in defining treatment-limiting antibiotic resistance called ‘difficult-to-treat resistance (DTR).’”

“As a bedside clinician with a sick patient in front of me, I want to know, do I have at least one safe and effective antibiotic to treat the patient,” Kadri-Rodriguez explained. “If the answer to this is no, that strain I call DTR.”

Between the first quarter of 2016 and the second quarter of 2021, ceftolozane-tazobactam and ceftazidime-avibactam predominated the use of newer antibiotics, which had a “relatively sluggish uptake,” Kadri-Rodriguez and colleagues wrote.

Among 362,142 hospital encounters for gram-negative infections, 0.7% were categorized as DTR pathogens, according to the researchers.

Patients with DTR pathogens were treated exclusively with traditional generic agents in 41.5% of DTR episodes, including 79.3% of DTR episodes where “these older agents were agents with known suboptimal safety and/or efficacy such as polymyxins, aminoglycosides, and tigecycline,” the researchers noted.

Additionally, one-third of hospitals — which tended to be smaller hospitals in rural areas or in urban areas with low prevalence of resistance — never used newer antibiotics.

Kadri-Rodriguez noted that there were no significant differences in age, gender, race, ethnicity, insurance status or ICU status.

He concluded that new antibiotics “continued to be underutilized” against DTR pathogens.

“Clinicians still often prescribe toxic [and] sub-efficacious agents, often in patients with DTR infections,” Kadri-Rodriguez said. “Agents are needed with innovative mechanisms targeting pathogens without good treatment options.”

He also added that there is a need “to expand access to antibody susceptibility testing for these new agents as soon as they come out,” which could help “bridge the unmet patient need in future antibiotics.”

In a related editorial, Jessica Howard-Anderson, MD, MSc, an assistant professor of medicine at Emory University, and Helen W. Boucher, MD, a professor of medicine at Tufts University School of Medicine, pointed out that antimicrobial development can be time-consuming, costly and uncertain when it comes to success.

However, with antimicrobial resistance (AMR) estimated to contribute to 1.2 million annual deaths globally, “we need to ensure that new antibiotics are not only being developed but also effectively used,” they wrote.

Howard-Anderson and Boucher added that further efforts “to raise awareness, innovation in pathogen-specific trials, regularly updated AMR guidance, patient-centered end points, and rapid susceptibility testing will be key to appropriate and optimal use of these new antibiotics.”

References:

• Anderson-Howard J, Boucher H. Ann Intern Med. 2024;doi:10.7326/M24-0192.
• Kadri-Rodriguez SS, et al. New in Annals of Internal Medicine: Hear it first from the authors. Presented at: ACP Internal Medicine Meeting; April 18-20, 2024; Boston.
• Strich J, et al. Ann Intern Med. 2024;doi:10.7326/M23-2309.