In a recent study, researchers from the Shenzhen Third People’s Hospital and BGI-Research have explored the clinical potential of phage treatment for pulmonary infection caused by Serratia marcescens (S. marcescens), a common bacterium with refractory multidrug-resistant in nature. The team has successfully identified a phage that is appropriate for S. marcescens infection and demonstrated its effectiveness by alleviating the symptoms in a patient, offering a new approach to tackling the challenge of antibiotic resistance. The findings were published in Emerging Microbes & Infections.
The study “Exploration of the feasibility of clinical application of phage treatment for multidrug-resistant Serratia marcescens-induced pulmonary infection” was published in Emerging Microbes & Infections.
S. marcescens is a common gram-negative opportunistic pathogen that can infect a wide range of hosts, including insects, plants, mammals, and humans. It often affects people with weakened immune system, such as newborns and patients in intensive care units (ICU), and may cause systemic infections, particularly those in the respiratory system, urinary tract, wounds, and bloodstream. These infections pose a significant challenge in healthcare settings because the bacterium is naturally resistant to many antibiotics, including β-lactams, aminoglycosides, fluoroquinolones, macrolides, and cationic antimicrobial peptides. Infections caused by S. marcescens can be fatal, with mortality rates ranging from 0% to 45%, according to studies.
Phages, or bacteriophages, are a diverse group of viruses commonly found in nature. These viruses exhibit remarkable specificity toward bacterial hosts, infecting and lysing specific “harmful” bacterial strains, whereas leaving “beneficial” microbiota unaffected. Some phages are considered as potential therapeutic agents due to their key characteristics such as strong lytic activity, a broad host range, and high tolerance. Phage therapy has been widely applied to address a range of challenging pathogens; however, there are no reports on the use of phages for the treatment of S. marcescens infections.
In this study, researchers utilized genome sequencing and analysis capabilities to identify a specific phage named Spe5P4, which lacks virulence, lysogenic, and antibiotic-resistance genes. These characteristics make it an ideal candidate for therapeutic use due to its safety profile.
A 59-year-old male patient with multidrug-resistant S. marcescens thoracic infection was treated using phage Spe5P4 in combination with conventional antibiotics. The treatment led to significant improvement in the patient's clinical symptoms, and lung imaging showed that the infection was effectively controlled. Throughout the treatment process, no abnormalities were observed in liver and kidney functions or immunity indexes, and no obvious adverse reactions were reported. More importantly, the study found no evidence of the target bacteria developing resistance to the phage, further confirming the stability and reliability of phage therapy.
Changes in chest CT and hydrothorax morphology before and after phage treatment:(A) Representative chest CT images before (blue) and after phage treatment (green). Blue arrows present the lung tissue, red arrows present the pleural fluid. Before phage treatment, the lung tissue (black parts marked with a blue arrow) was markedly compressed indicating notable atelectasis. These black parts recovered slowly, indicating a slow recovery of atelectasis before phage administration. The pleural fluid (marked with a red arrow) was large and remarkable. The reduction in this part was slow, indicating slow absorption of the inflammatory hydrothorax. However, after phage treatment, the lung tissue achieved fast recovery, and the pleural fluid became smaller. At the end of follow-up, the lung tissue significantly recovered, and the pleural fluid was greatly aborted. Thus, phage treatment contributed to better amelioration of pulmonary conditions. (B) Appearance of the hydrothorax collected by thoracentesis. The hydrothorax became clear.
“Phage therapy for S. marcescens infections offers a fresh approach to tackling the challenge of antibiotic resistance. It also paves the way for exploring precise treatments for other drug-resistant bacteria,” explained Professor Hongzhou Lu, co-corresponding author of the study and the President of the Shenzhen Third People's Hospital. “As this technology continues to advance and be applied, phage therapy has the potential to become a key tool in clinical anti-infection treatments, bringing real benefits to patients."
Dr. Minfeng Xiao, co-corresponding author of the study and a researcher at BGI-Research, said, “By leveraging BGI's technological strengths in genomic research, constructing a large-scale phage biobank, and employing high-throughput screening and preparation of phages, we aim to jointly explore novel therapeutic approaches for combating multidrug-resistant bacteria. We hope to advance research and clinical applications in the field of phage therapy, providing a reference solution to address the challenge of antibiotic resistance.”
This study was conducted in strict accordance with the guidelines of the World Medical Association’s Declaration of Helsinki and was approved by the ethics committee of the Third People's Hospital of Shenzhen. Written informed consent was obtained from the patient.
This study can be accessed here: https://doi.org/10.1080/22221751.2025.2451048
Source:
Zivkovic Zaric, Radica, Milan Zaric, Marija Sekulic, Nenad Zornic, Jelena Nesic, Vesna Rosic, Tatjana Vulovic, Marko Spasic, Marko Vuleta, Jovan Jovanovic, and et al. 2023. "Antimicrobial Treatment of Serratia marcescens Invasive Infections: Systematic Review" Antibiotics 12, no. 2: 367. https://doi.org/10.3390/antibiotics12020367