IDWeek 2024 continues to provide more and more infection control and prevention studies to improve lives. Infection Control Today (ICT) presents interviews with CSL Seqirus and Shionogi about their presentations at IDWeek.

These studies were presented at IDWeek, 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 in Los Angeles from October 16 to 19, 2024.

CSL Sequirus

According to a dynamic model, increasing vaccination rates to at least 45% could alleviate pressure on hospital systems, particularly intensive care units (ICUs), during peak flu seasons. With vaccination rates currently at approximately 35%, experts warn that the health care system faces significant strain.

The studies also demonstrated the superior effectiveness of cell-based influenza vaccines compared to egg-based alternatives. Real-world evidence (RWE) from the 2022-23 flu season revealed that cell-based vaccines were more effective at preventing outpatient-confirmed influenza across all age groups, including children as young as six months. Modeling estimates suggest switching to cell-based vaccines could significantly reduce flu-related illnesses, hospitalizations, and costs.

"In the face of declining seasonal influenza immunization rates, our dynamic model analysis shared at IDWeek 2024 highlights a pressing and critical need to elevate US vaccination rates,” said Joaquin Mould-Quevedo, the senior director of global health economic and value strategy at CSL Seqirus to ICT. “Evidence shows that higher influenza vaccination rates significantly reduce serious health consequences, including severe illness, hospitalizations, and death. Last season’s rates dropped, increasing the risk of our health care system becoming overwhelmed. These data underscore an urgent need to increase vaccination rates to at least 45% to avoid overburdening our health systems and ensure that our hospital resources, especially ICU beds, are not overwhelmed.”

Experts at CSL Seqirus emphasized the critical role of cell-based vaccines in protecting vulnerable populations and improving public health outcomes. The company’s innovative digital tools, like the Polyphonic ecosystem, aim to enhance patient monitoring and vaccination reporting. The findings underscore the importance of improving flu vaccination rates and adopting advanced vaccine technologies to ease health care system burdens and improve patient care globally.

"Real-world evidence is an important consideration in vaccine research as it provides insights that extend beyond the controlled settings of clinical trials, capturing the true impact of vaccines in diverse environments,” said Mendel Haag, the senior director of the Center of Outcomes Research & Epidemiology at CSL Seqirus. “Our data presented at IDWeek demonstrates the potential benefits that cell-based influenza vaccines can offer over traditional egg-based alternatives across all age groups. In addition, first-season findings from our study offer critical insights into the comparative effectiveness of adjuvanted and high-dose vaccines for adults aged 65 and older. This ongoing, multiseason study is pivotal in advancing our mission to enhance and protect public health on a broader scale."

Shionogi

Innovative treatments like cefiderocol have become critical in the fight against serious Gram-negative bacterial infections. Infection Control Today® (ICT®) interviewed Simon Portsmouth, MD, FRCP, senior vice president and head of clinical development at Shionogi Inc., to discuss the groundbreaking findings from the PROVE (retrospective cefiderocol chart review) study.

Portsmouth discusses the importance of real-world evidence in complementing randomized controlled trial data, the methodology behind the study, and the promising results showing the efficacy and safety of cefiderocol in treating difficult-to-treat Gram-negative infections. With insights into its effectiveness across infection types and its potential against resistant pathogens, this interview offers valuable perspectives for health care professionals tackling the challenges of antimicrobial resistance.

ICT: What was the primary motivation or research question that led you to conduct this study, and why is it important?

Simon Portsmouth, MD, FRCP: The primary goal of the PROVE (retrospective cefiderocol chart review) study was to evaluate how patients with certain serious Gram-negative (GN) bacterial infections respond to cefiderocol in real-world clinical settings.¹

While randomized controlled trials (RCTs) are the basis for approval of treatment options, they can be difficult to conduct for antibiotics and present limitations in understanding the impact of these treatments in real-life clinical settings.^2,3,4 Real-world evidence, such as that from the PROVE study, can complement clinical trial data by helping us in our clinical decision-making and a better understanding of responses to cefiderocol in diverse patient populations, including across different infection sites and pathogens.^1,5

ICT: Can you briefly explain the methodology you used in the study

SP: PROVE is a retrospective, real-world study that analyzed clinical outcomes in 1,075 seriously ill, hospitalized patients treated with cefiderocol for certain GN bacterial infections.¹ The study aimed to capture a broad, real-world patient population, reflecting the diversity of infection types and sites, disease severity, and geographic locations.¹Most participants had infections caused by bacteria in the World Health Organization’s list of priority pathogens.⁶ To be included in the study, patients had to receive at least 72 hours of cefiderocol for the first time for a documented GN bacterial infection.¹ Additionally, participants had to have information about cefiderocol starting dose, description of the GN bacterial infection, and discharge data after hospitalization.¹

By including different infection sites and pathogens, the study provided comprehensive insights into the effectiveness of cefiderocol across patient populations, complementing clinical trial data with real-world evidence.¹

ICT: What were the key findings of your study, and how do they contribute to the existing body of knowledge in your field?

SP: The key finding from the PROVE study showed the majority (75.1%) of patients had a clinical response to cefiderocol at the end of treatment.¹ Clinical response was defined as the resolution or improvement of signs and symptoms of the infection, as judged by the physician at the end of cefiderocol treatment (EOT). Looking at the breakdown by top primary infection sites, we saw high response rates, including 71.6% for respiratory tract infections, 74.1% for bloodstream infections, and 91.2% for urinary tract infections.¹ Cefiderocol was generally well-tolerated, with 13 patients discontinuing treatment due to adverse reactions.¹ Twenty-nine adverse drug reactions in 25 of 1,075 patients were reported, three of which were serious.¹ These findings further build on our clinical trial data for cefiderocol by supporting its use in seriously ill patients with certain difficult-to-treat GN infections in both controlled clinical trials and real-world settings.¹
At IDWeek, we shared in vitro studies that showed cefiderocol had activity against resistant GN bacteria that show high degrees of cross-resistance to contemporary beta-lactam/beta-lactamase inhibitor (BL/BLI) combinations.^7,8 Cross-resistance occurs when bacteria are resistant to multiple distinct antibiotics through the same mechanism(s), and it can further limit treatment options for multidrug-resistant bacteria.^9,10

We also shared in vitro studies that showed cefiderocol maintained activity against highly resistant metallo-beta-lactamase-producing bacteria.^11,12 Metallo-beta-lactamases (MBLs) are enzymes that can inactivate most beta-lactams, the most commonly used antibiotics around the world, and their increasing prevalence worldwide is adding to the growing challenge of antibiotic resistance.^13,14,15

Though in vitro activity does not necessarily correlate with clinical efficacy, we believe these data highlight the utility of cefiderocol for drug-resistant infections, including isolates that showed resistance against BL/BLI combinations or those carrying MBL genes, which have limited options and are difficult to treat.^7,8,11,12

Resources:

Cefiderocol Prescribing Information

Cefiderocol Important Safety Information

References:

1. Clancy C, et al. Real-world effectiveness and safety of cefiderocol in the treatment of patients with serious gram-negative bacterial infections: Results of the PROVE Chart Review Study. Poster presented at IDWeek 2024.
2. Redell M. Real-world evidence studies of oritavancin use in gram-positive infections augment randomized controlled trials to address clinical and economic outcomes. Drugs Real World Outcomes. 2020;7(Suppl 1):2-5.
3. Paterson DL, Sulaiman HB. "Real-world" evidence, target trial emulation, and randomized clinical trials—Which data should clinicians rely on when choosing antibiotics? JAMA Netw Open. 2024;7(1):e2352250. doi:10.1001/jamanetworkopen.2023.52250.
4. Dang A. Real-world evidence: A primer. Pharmaceut Med. 2023;37(1):25-36. doi:10.1007/s40290-022-00456-6. Epub January 5, 2023. PMID: 36604368; PMCID: PMC9815890.
5. Williams DM, et al. The evolution of real-world evidence in healthcare decision-making. Expert Opin Drug Saf. 2023;22(6):443-445. doi:10.1080/14740338.2023.2224559.
6. World Health Organization. WHO bacterial priority pathogens list, 2024. Accessed September 2024. http://iris.who.int/bitstream/handle/10665/376776/9789240093461-eng.pdf?sequence=1.
7. DeJonge B, et al. Cefiderocol retains in vitro activity against Enterobacterales non-susceptible to β-lactam-β-lactamase inhibitor combinations. Talk presented at IDWeek 2024.
8. Nguyen S, et al. Evaluation of phenotypic cross-resistance between cefiderocol and β-lactam/β-lactamase inhibitor combinations against Pseudomonas aeruginosa isolates from US medical centers. Poster presented at IDWeek 2024.
9. Colclough A, Corander J, Sheppard SK, Bayliss SC, Vos M. Patterns of cross-resistance and collateral sensitivity between clinical antibiotics and natural antimicrobials. Evol Appl. 2019;12(5):878-887. doi:10.1111/eva.12762. PMID: 31080502; PMCID: PMC6503891.
10. Anderson M, et al. Challenges and opportunities for incentivizing antibiotic research and development in Europe. Lancet Reg Health Eur. 2023;22:100586. doi:10.1016/j.lanepe.2023.100586.
11. Mendes RE, et al. Cefiderocol activity against Pseudomonas aeruginosa clinical isolates carrying metallo-β-lactamase genes in United States and European hospitals (2020–2023). Poster presented at IDWeek 2024.
12. Mendes RE, et al. Cefiderocol activity against clinical Enterobacterales isolates carrying metallo-β-lactamase genes in United States and European hospitals (2020–2023). Poster presented at IDWeek 2024.
13. Boyd SE, et al. Metallo-β-lactamases: Structure, function, epidemiology, treatment options, and the development pipeline. Antimicrob Agents Chemother. 2020;64(10):e00397-20. doi:10.1128/AAC.00397-20. PMID: 32690645; PMCID: PMC7508574.
14. Bertagnolio S, et al. Antimicrobial resistance: Strengthening surveillance for public health action. PLoS Med. 2023;20(7):e1004265. doi:10.1371/journal.pmed.1004265.
15. Kanannejad Z, et al. Diagnosis and selection of alternative antibiotics in beta-lactam hypersensitivity reactions: Current recommendations and challenges. Int Immunopharmacol. 2023;122:110573. doi:10.1016/j.intimp.2023.110573.