Antibiotics
Terri D’Arrigo
FDA approved seven next-generation gram-negative antibiotics between 2014 and 2019. Yet a study published in the May 2024 issue of the Annals of Internal Medicine found that between 2016 and 2021, clinicians in 619 U.S. hospitals treated more than 40% of patients who had highly antibiotic-resistant pathogens exclusively with older, generic agents. Furthermore, most of these older agents had known suboptimal safety and/or efficacy.
“Treating highly resistant pathogens with older, generic agents poses several dangers,” said study researcher Willy Li, PharmD, a critical care clinical pharmacist at the National Institutes of Health Clinical Center. Li said that polymyxins and aminoglycosides are characterized by suboptimal pharmacokinetics and a narrow therapeutic index with high rates of nephrotoxicity. He added that other older agents such as tigecycline have higher rates of treatment failure and all-cause mortality compared to other first-line options.
“Given these dangers, it’s important for clinicians to consider using newer and potentially safer agents to treat highly resistant pathogens,” Li said. “However, the decision should be based on factors such as the patient’s condition, the susceptibility of the pathogen, and the potential risks and benefits of each treatment.”
Why the slow uptake?
When making decisions on which antibiotic to prescribe, clinicians often look to the literature for evidence that one antibiotic will be more effective or safer than another. However, they may not be finding the kind of evidence they seek, said Li.
“Patients with resistant pathogens are poorly represented in the trials that led to the approval of the newer antibiotics,” Li said. “There is also a lack of evidence comparing novel agents head-to-head for treating highly resistant pathogens. Pharmaceutical companies may be hesitant to invest in such trials, especially if they perceive limited market potential or if they anticipate challenges in demonstrating [a new agent’s] superiority over other existing treatments.”
The researchers found several trends involving choice of antibiotics:
One-third of the hospitals that never used new antibiotics were smaller hospitals in rural areas or in urban areas with low rates of resistance.
Hospitals that reported antibiotic susceptibility testing for new agents were more likely to use newer agents.
Regional preferences for new agents reflected known regional differences in the epidemiology of difficult-to-treat resistant infections.
“These findings underscore a need to incentivize drug discovery, demonstrate improved outcomes in patients with resistant pathogens, and facilitate earlier/wider implementation of susceptibility testing for new agents to improve novel antibiotic uptake and utilization,” Li said.
Cost may also be a factor in antibiotic choice. The average wholesale price of the new agents in the study was $1,036.69, compared with $173.41 for traditional agents.
What pharmacists can do
Hospital pharmacists should work with other clinicians in ensuring that patients get the most appropriate antibiotics, including newer ones, but there must be a solid infrastructure to support it, said Ripal Jariwala PharmD, who was not involved in the research. Jariwala is an infectious diseases clinical pharmacist and an assistant clinical professor at the University of California, San Francisco.
“Infrastructure needs to be set up for oversight, antibiotic stewardship, and case management, with formal processes in place,” Jariwala said. “We also need to make sure our microbiology partners have the right platforms to do susceptibility testing for these newer agents and the personnel to [validate results].”
Jariwala added that pharmacists should stay abreast of the literature and refer to guidelines such as the Infectious Diseases Society of America’s 2023 Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. However, pharmacists should also communicate their own experiences both informally among their peers and formally by publishing research, she said.
“That’s where I challenge pharmacy leadership. Give staff protected time. Pay some of the publication fees for research,” she said. “Otherwise, there isn’t a lot of information, and we could be using agents that can change a patient’s course.”
Li stressed the importance of formulary management.
“Pharmacists can play a key role in formulary management by evaluating the safety, efficacy, and cost-effectiveness of new antibiotics compared to older agents,” Li said. “Depending on local resistance patterns and evidence-based guidelines, they can advocate for the inclusion of newer antibiotics and help develop restriction criteria to prevent misuse and promote stewardship.” ■