Editor’s Note: Klebsiella pneumoniae is a significant opportunistic pathogen capable of causing a range of infections, including pneumonia, urinary tract infections, bloodstream infections, and sepsis. In particular, infections caused by hypervirulent and multidrug-resistant strains of Klebsiella pneumoniae pose a substantial treatment challenge and have high mortality rates. Dr. Sheng Chen from the City University of Hong Kong, China, along with his team, has been dedicated to studying the mechanisms of drug resistance, epidemiological trends, and the development of new therapies for this "superbug." At the recently held 2nd One Health Microbial Resistance Control Conference (October 11-14, 2024, Hangzhou), Dr. Chen delivered a compelling report titled “Research Progress on Klebsiella pneumoniae” and shared his insights in an interview with Infectious Diseases Frontier.1. Infectious Diseases Frontier: What global challenges does Klebsiella pneumoniae, as a significant drug-resistant pathogen, pose to public health? What are the primary difficulties in controlling its infections?
Dr. Sheng Chen: Klebsiella pneumoniae infections have become a global health issue. The primary challenge stems from the pathogen’s ability to evolve into various clinical phenotypes, such as hypervirulent, multidrug-resistant (MDR), and the combination of both characteristics—creating a “superbug” known as MDR-hv Klebsiella spp. These different types of Klebsiella pneumoniae present considerable challenges for clinical treatment and control. Currently, there are fewer drugs available to effectively treat MDR-hv Klebsiella infections. Even newly introduced drugs, such as ceftazidime/avibactam, may start encountering resistance within two years, making treatment increasingly difficult.
Moreover, Klebsiella pneumoniae evolves rapidly and can mutate to adapt to different hospital infection control measures and treatment environments. Therefore, controlling its spread in the future is critical. Due to limited treatment options, infections caused by Klebsiella pneumoniae are associated with high clinical infection rates and mortality. In mainland China, Klebsiella pneumoniae is one of the most common pathogens responsible for bloodstream infections, second only to Escherichia coli. However, due to its higher virulence, Klebsiella pneumoniae infections result in much higher mortality rates, emphasizing the growing severity and urgency of this issue.
2. Infectious Diseases Frontier: At this conference, you shared some recent research advancements related to Klebsiella pneumoniae. Could you elaborate on the significant findings in terms of drug resistance mechanisms or prevalent clones?
Dr. Sheng Chen: Klebsiella pneumoniae exhibits a wide variety of serotypes and is prevalent in clinical settings. Its adaptability to different environments and the complex clonal transmission pose substantial challenges for clinical control. The rapid evolution of Klebsiella pneumoniae has led to the spread of previously uncommon clones in clinical settings. For example, serotype K1 hypervirulent Klebsiella pneumoniae (hvKp), which was not common previously, has become a leading serotype following large outbreaks in Europe.
Particularly concerning is the fact that some highly virulent strains of Klebsiella pneumoniae have acquired plasmids conferring carbapenem resistance, such as the carbapenemase-producing clonal complex 258 (CC258) group, which includes ST258, ST11, ST340, ST437, and ST512. These clones have spread rapidly in clinical settings.
However, predicting the future evolution of Klebsiella pneumoniae remains challenging. As infection control measures and environmental conditions change, Klebsiella pneumoniae could evolve into new and more easily transmissible clones. Therefore, controlling Klebsiella pneumoniae is an urgent issue in clinical settings.
3. Infectious Diseases Frontier: The clinical treatment of carbapenem-resistant Klebsiella pneumoniae (CRKP) and other drug-resistant pathogens is a major challenge. What new antimicrobial agents have shown promise in treating CRKP infections? Could you share any research advancements in this area?
Dr. Sheng Chen: The primary antimicrobial agent currently used to treat multidrug-resistant Klebsiella pneumoniae infections is ceftazidime/avibactam. Other drugs, such as tigecycline, are still in use, but their effectiveness is limited and they may even pose risks. Data shows that tigecycline could promote the persistence of Klebsiella pneumoniae in the gut, bloodstream, or environment. Colistin, another treatment option, also has poor efficacy and tends to lead to rapid resistance development.
Due to the limited treatment options, many researchers and scientists are actively developing new therapies. For example, our team has developed several new therapeutic approaches. To address colistin resistance, we developed a new colistin combined with an adjuvant (e.g., otilonium bromide), which enhances its antimicrobial activity even against colistin-resistant Klebsiella pneumoniae and reduces the likelihood of resistance developing quickly. Additionally, we have explored the combined oral use of zidovudine and rifampin, both older drugs, which has shown promising effects. We are also working on developing new drugs similar to ceftazidime/avibactam, such as new KPC-2 inhibitors that target resistant strains. Our team has identified multiple drugs that show excellent therapeutic effects and are now moving towards further clinical research and eventual clinical application.
However, even with new treatment approaches, we cannot become complacent. Klebsiella pneumoniae may evolve again, developing resistance to the newly developed drugs. Therefore, the battle against multidrug-resistant Klebsiella pneumoniae must be ongoing. We need to continuously develop new treatment methods to tackle the emerging resistance.
4. Infectious Diseases Frontier: What are your expectations for this year’s One Health Microbial Resistance Control Conference? How do you think we should push forward global efforts to control antimicrobial resistance?
Dr. Sheng Chen: I believe that making antimicrobial resistance (AMR) control the central theme of this conference is a significant breakthrough, aligning with our current needs and sending a clear call to action. In the past, much of the research on resistance focused on understanding its mechanisms and current levels. However, we must now go beyond understanding and proactively address how to control it. With a considerable understanding already in place, we must clearly target AMR control in the future.
The One Health approach underpins this conference, highlighting that controlling resistance cannot be achieved solely by hospitals. It requires a collaborative effort from all stakeholders under the One Health framework. The content of this conference is diverse and the discussions are in-depth. Even if in the first few conferences, we may not have comprehensive solutions to control resistance, I believe that as awareness deepens and researchers align their efforts towards controlling AMR, we will see diverse attempts and initiatives emerge. In a few years, we might witness the development of innovative and effective strategies to combat AMR.
