Editor's Note: In recent years, the problem of drug resistance has intensified, and carbapenem-resistant organisms (CRO), representing multiple drug-resistant bacteria, have imposed a significant disease burden globally. Patients with blood diseases are at high risk of CRO and other infections due to compromised immune function, either due to the primary disease or treatment-related factors. These infections often present with atypical clinical manifestations, unclear or hard-to-detect infection sites, and a low positive rate in pathogen culture. Metagenomic Next-Generation Sequencing (mNGS), as a high-throughput detection technology covering a broad pathogen spectrum, aids in diagnosing pathogens in blood disease infections. At the recently held Fourth China Hematology Development Conference, Professor MingGui Wang , the head of the Antibiotics Research Institute at Huashan Hospital affiliated with Fudan University, presented an excellent report titled "Global Prevalence and Antimicrobial Treatment Progress of CRO". Infectious Disease Frontline had the opportunity to interview Professor MingGui Wang at the event, where he shared insights on the value of mNGS in the pathogen diagnosis of blood disease infections, the progress of new drug research on global CRO infections, and the importance of multidisciplinary exchanges in the field of hematology.
Infectious Disease Frontline: The “Chinese Expert Consensus on the Application of Metagenomic Next-Generation Sequencing Technology in the Diagnosis of Pathogens in Blood Disease Infections” has been published. How do you view the value of mNGS in the diagnosis of pathogen infection in blood diseases? How should the results of mNGS be correctly interpreted and guide anti-infection treatment?
Professor MingGui Wang : mNGS technology has been widely used in the diagnosis of pathogens in clinical infectious diseases, especially suitable for patients with blood disease infections, as these patients often have atypical clinical manifestations of infection, unclear or hard-to-detect infection sites, and a low positive rate in pathogen culture. mNGS allows for rapid, high-throughput sequencing of samples like peripheral blood, providing more comprehensive and relatively unbiased pathogen information, which plays a positive role in diagnosing infection pathogens. The formulation of this expert consensus also facilitates the standardized application of mNGS in the diagnosis of blood disease infection pathogens.
Regarding the optimal use of mNGS, I believe the following two points are crucial: First, the indications for mNGS, it’s very important to clearly identify which patients should be tested and what samples to send for testing. At this stage, traditional microbiological testing remains the first choice for suspected infection patients. mNGS is often chosen under special circumstances, such as when traditional microbiological testing takes a long time to identify the pathogen, and in cases of severe infections and central nervous system infections where the positive rate of culture is low, potentially leading to delayed appropriate treatment and exacerbation of the infection. Regarding the samples to be tested, it’s preferable to collect directly from the infection site; if not possible, peripheral blood samples can be considered. Second, the interpretation of results, the number of detected sequences can provide some reference for the clinic, but this does not mean that high sequence detection is meaningful while low sequence detection is not. For pathogens that are clearly pathogenic and rarely colonize, low sequence detection should also be considered potentially pathogenic. In mNGS reports, we often see low sequence numbers for fungi and high numbers for bacteria like Acinetobacter baumannii. Whether these findings are clinically significant should be interpreted in the context of the patient’s underlying conditions and clinical manifestations.
Infectious Disease Frontline: At the conference, you presented an excellent report titled “Global Prevalence and Antimicrobial Treatment Progress of CRO”. What are some notable new antimicrobials globally in response to CRO infections?
Professor MingGui Wang : Overall, there has been an increase in new drugs for treating CRO infections in recent years, which is good news for professionals involved in the diagnosis and treatment of drug-resistant bacterial infections. These new antimicrobials can be categorized into three main types:
The first category includes β-lactamase inhibitor combination drugs, which have developed rapidly in recent years. Drugs that have been approved mainly have antimicrobial activity against Enterobacterales producing serine carbapenemases (like KPC enzymes), including ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam. Drugs targeting bacteria producing metallo-enzymes like NDM, such as cefiderocol-taniborbactam, have completed Phase III clinical trials and are expected to be approved for clinical anti-infection treatment soon. Another special enzyme inhibitor combination is durlobactam-sulbactam, which consists of two enzyme inhibitors; sulbactam acts as an antimicrobial, while durlobactam acts as an inhibitor. This drug shows good antimicrobial activity against carbapenem-resistant Acinetobacter baumannii (CRAB). Phase III clinical trials demonstrated its efficacy in severe infections caused by the CRAB-Acinetobacter calcoaceticus complex is not inferior to control drugs, and it has good safety. After the interim results of the clinical trial were published, the drug was approved in the United States in 2023.
The second category is tetracycline derivatives. Previously, tigecycline had been approved for treating infections caused by carbapenem-resistant Enterobacterales (CRE) and CRAB. Recently, more tetracycline drugs have been added, such as eravacycline and omadacycline. Eravacycline’s in vitro antimicrobial activity against CRE and CRAB is 2 to 8 times that of tigecycline, and it has higher tissue concentrations, making it more suitable for treating CRO infections.
The third category includes polymyxin-class drugs, which have been on the market for a long time and have been used globally. However, their clinical application in China is still on the rise due to limited drugs approved for CRO infections. Additionally, many new derivatives of polymyxins are undergoing clinical research, with a focus on optimizing their toxicity reactions, which is of clinical interest.
Additionally, cefiderocol is a new antimicrobial worth attention. It has in vitro antimicrobial activity against CRAB, CRE, and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Cefiderocol has already been approved abroad and is currently undergoing Phase III multicenter studies in China. This summarizes the current global research on new drugs for CRO infections.
Infectious Disease Frontline: During the BISC conference, you emphasized the importance of a multidisciplinary approach to bacterial and fungal infections and resistance issues. Now at a hematology conference, as an infectious disease expert, what are your thoughts and experiences?
Professor MingGui Wang : I am delighted to participate in this China Hematology Development Conference. The majority of the experts and scholars at the conference are from the field of hematology, and I am pleased to see many experts from the field of infection also participating, which is beneficial for the development of both hematology and infectious diseases. The conference included a forum on infection, discussing topics such as drug-resistant bacteria, fungi, viruses, and mNGS pathogen diagnostic methods. Therefore, it’s evident that experts from multiple disciplines like hematology, infectious diseases, respiratory medicine, and microbiological testing were present, indicating the importance the field of hematology places on research in infections. This conference provided an opportunity and platform for communication among multidisciplinary experts. I hope that through such academic exchanges, we can share new knowledge, technologies, and concepts related to infections with colleagues from various fields. By integrating different disciplines, we aim to continually optimize diagnostic and treatment strategies for infections in patients with hematologic diseases and contribute to improving clinical diagnostic and treatment levels.
