SINGAPORE - A century-old treatment that uses viruses to attack bacteria was successfully used in 2024 to save the life of a Singapore General Hospital (SGH) patient who had exhausted all care options for an antibiotic-resistant infection.
This made her the first patient in South-east Asia to benefit from phage therapy, which uses viruses called bacteriophages (or phages) to selectively target and kill bacteria, the hospital said on March 25.
The treatment was popularised in the early 20th century, but the mass production of antibiotics led to its demise in Western medicine. With antimicrobial resistance a major global health threat, there is now growing interest in this old approach as a promising treatment for difficult-to-treat infections.
Dr Jasmine Chung, a senior consultant at SGH’s department of infectious diseases, said such infections could be due to superbugs or bacteria that are well shielded in biofilm and often grow on implanted medical devices, making it difficult for antibiotics to reach them.
Associate Professor Andrea Kwa (left), SGH deputy director of pharmacy (research and innovation), alongside Dr Jasmine Chung, senior consultant in SGH’s department of infectious diseases.ST PHOTO: NG SOR LUAN
The SGH patient, Ms A, who is in her 30s and has congenital heart disease, had developed a hard-to-treat infection in her chest cavity and blood after undergoing complex surgery to put in a vascular and heart valve implant in January 2024. It was her fifth operation.
The culprit bacteria was Pseudomonas aeurginosa, a common organism known to cause serious, difficult-to-treat infections.
That left the patient, a mother of an infant and toddler, with two bleak choices. The first was to undergo an extremely risky operation to remove the infected implant.
The second was to remain on intravenous antibiotics – administered through a silicone tube placed in a vein in her arm – for the long term, and live with a chronic infection.
Ms A opted to be placed on a prolonged course of intravenous antibiotics, and was hospitalised repeatedly in 2024.
She kept having recurrent infections as the source of the infection could not be removed by the antibiotics.
To treat her, the SGH team used phage therapy in combination with antibiotics.
While it was difficult for antibiotics to reach the culprit bacteria that were shielded in biofilm, phages were able to do so by breaking down the biofilm, Dr Chung said.
The treatment was administered intravenously, and the two-week course treated the infection effectively. It meant that Ms A did not need high-risk surgery and was able to move from intravenous to oral antibiotics.
“Phages are like little soldiers,” said Associate Professor Andrea Kwa, deputy director of pharmacy (research and innovation) at SGH.
When they find a bad bacterium, they infiltrate it and “hijack the bacterial machinery”, replicating themselves within the cell walls. Eventually, the bacterium bursts open and dies, she said.
Phages are highly host-specific, targeting only the harmful bacteria they are programmed to eliminate and leaving other bacteria alone, unlike antibiotics, she said.
A challenge with phage therapy is finding the right phages that can precisely target the harmful bacterial strains, Dr Chung said.
Another key challenge is purifying and producing the phages, she added.
Senior medical laboratory scientist Thong Shuhua collecting a soil sample on SGH grounds to test for phages.ST PHOTO: NG SOR LUAN
Phages, which do not infect human cells, are the most abundant commonly occurring natural entities, existing in bodies of water and soil and even on humans and animals.
The SGH team treating Ms A had started building its library of more than 100 catalogued phages and complex production processes in 2021, as it was preparing to use the therapy for a small but growing group of patients with difficult-to-treat infections.
Samples of phages at Singapore General Hopsital. The hospital currently has more than a hundred samples.ST PHOTO: NG SOR LUAN
When the team was ready for the first patient, it had to match her unique bacterial strains against the SGH library of more than 100 catalogued phages and the phages collected by the team’s research collaborators from other institutions.
In all, the phage screen, test and production of the safe phage formulation took the team about five months. The treatment was given to Ms A in September 2024.
“We developed a cocktail of three phages that could work synergistically with the antibiotics she was put on to increase the latter’s potency and fight the infection,” said Prof Kwa.
“This prevents further emergence of bacterial resistance and ensures thorough eradication of the culprit bacteria.”
Elsewhere in South-east Asia, there is interest in the therapy – with research being done in Malaysia, for instance – but the SGH team is the first to use it clinically in the hospital, Prof Kwa added.
The SGH team has administered phage therapy to two other patients since 2024 and will be administering it to two more patients in April. They have mostly implant-related infections involving similar bacterial strains.
Currently, phages are used here on compassionate grounds when all other treatments have been exhausted.
Dr Chung and Prof Kwa said they are working with the regulatory authorities to develop a framework for phage therapy to be used in more patients.
