A considerable proportion of clinicians, particularly at smaller facilities located in rural areas, are reluctant to adopt newer antibiotics, an NIH study finds.

RT’s Three Key Takeaways:

  1. Despite FDA approval of seven next-generation antibiotics designed to combat resistant gram-negative bacterial infections between 2014 and 2019, US hospitals frequently opt to use older, generic antibiotics. Researchers say these traditional antibiotics are often less effective and pose greater safety risks, with more than 40% of patients with highly resistant pathogens being treated exclusively with these older options.
  2. Among the new antibiotics, ceftolozane–tazobactam and ceftazidime–avibactam saw the most significant increase in use from 2016 to 2019. Other next-generation antibiotics like meropenem–vaborbactam and cefiderocol had much lower usage rates, with plazomicin seeing no use at all.
  3. The high cost of new antibiotics—about six times that of older drugs—coupled with reimbursement models in the US healthcare system, disincentivizes their use. Hospitals that perform antibiotic susceptibility testing are more likely to prescribe these newer agents. Clinicians prefer new antibiotics particularly for treating complex cases such as difficult-to-treat bloodstream infections or patients with high comorbidity burdens.

Despite the US Food and Drug Administration (FDA) approving seven next-generation antibiotics to fight infections caused by resistant “gram-negative” bacteria between 2014 and 2019, clinicians in the US frequently continue to treat antibiotic-resistant infections with older generic antibiotics considered to be less effective and less safe, according to a study by researchers at the National Institutes of Health’s (NIH) Clinical Center.

The study found that hospitals still treated more than 40% of patients battling highly resistant pathogens exclusively with the older, generic agents and that nearly 80% of the time these older agents are already known to be highly toxic or sub-optimally effective. 

The findings were presented at a breaking news scientific plenary session during the American College of Physician’s Internal Medicine Meeting 2024. The paper also is published in Annals of Internal Medicine.

Adoption of FDA-Approved Gram-Negative Antibiotics

Researchers retrospectively studied data from a large administrative database to determine inpatient use patterns of recently approved gram-negative antibiotics, including: 

  • ceftazidime–avibactam, 
  • ceftolozane–tazobactam, 
  • meropenem–vaborbactam, 
  • plazomicin, 
  • eravacycline, 
  • imipenem–relebactam–cilastatin, 
  • and cefiderocol.  

The researchers found that ceftolozane–tazobactam and ceftazidime–avibactam, the two first “next-generation” b-lactam/b-lactamase inhibitor antibiotics approved by the FDA, had the largest increase in use between 2016 and 2019. 

However, utilization of other next-generation antibiotics, including meropenem–vaborbactam, eravacycline, imipenem–cilastatin–relebactam, and cefiderocol was much lower, with no documented use of plazomicin (the manufacturer of which latter filed for bankruptcy).

Cost and Clinical Factors Influence Hospital Choices

Researchers also sought to identify factors associated with the preferential use of newer antibiotics over traditional generic agents. Clinicians seemed to prefer newer agents to treat patients with difficult-to-treat bloodstream infections and those with a high comorbidity burden. 

At the hospital level, some important factors associated with new versus traditional agent use were identified. For example, a third of study hospitals never used new antibiotics, and those tended to be small hospitals in rural areas or in urban areas with low prevalence of resistance. 

New antibiotics were also about six times more expensive than older agents, which could disincentivize prescribing given the way hospitals are reimbursed for care in the US. A lack of hospital access to a new agent did not seem to be a major factor for underutilization but hospitals that reported antibiotic susceptibility testing against new antibiotics tended to prescribe them more. 

Calls for Enhanced Utilization Strategies Amid Rising Antibiotic Resistance

According to the study authors, these findings underscore the need to prioritize unmet patient needs in future economic incentives for the failing antibiotic industry (such as the recent PASTEUR bill).

The authors of an accompanying editorial from Tufts University School of Medicine say that with antimicrobial resistance estimated to cause 1.2 million deaths globally per year, it’s important to ensure that new antibiotics are not only being developed but also effectively used. Getting an antibiotic to market takes 10 to 15 years and can cost up to a $1 billion. 

The editorialists commend the study authors for investigating what happens after antibiotics are approved. They suggest that continued efforts to raise awareness, innovation in pathogen-specific trials, regularly updated guidance, innovative patient-centered end points, and rapid susceptibility testing will be key to appropriate and optimal use of these new antibiotics.

Gram-negative bacteria are a class of bacteria resistant to multiple drugs and increasingly resistant to most antibiotics. According to the Centers for Disease Control and Prevention, they are able to find new paths of resistant and pass along genetic material that enables other bacteria to become drug resistant.

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