Singapore, 25 March 2025 – Refractory infections – those that do not respond to conventional treatments like antibiotics – can lead to a slew of issues, including increased morbidity and mortality, fewer treatment options and compromised medical procedures. But a treatment popularised in the early 20th century before the advent of antibiotics might provide an answer to treating such infections. A patient at Singapore General Hospital (SGH) was the first in Southeast Asia to have benefited from this century-old treatment as she no longer had other standard of care options.
Known as phage therapy, it is a special treatment that uses viruses called bacteriophages (or phages) to fight bacteria. Phages are like little soldiers. 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 in a process known as lysis. Phages are highly specific, targeting only the harmful bacteria they are programmed to eliminate and leaving other bacteria alone. This makes them highly efficient at eradicating bacteria that is difficult to clear.
Dr Jasmine Chung, Senior Consultant, Department of Infectious Diseases, SGH, said, “In tackling refractory infections, phage therapy has emerged as a promising alternative. Particularly for patients who have exhausted all conventional treatments when trying to combat difficult-to-treat infections. This could be due to superbugs, or bacteria which are well shielded in biofilm (tissue) that often grows on implanted or indwelling medical devices, making it difficult for antibiotics to reach them.”
Ms A, in her 30s, had undergone a complex heart surgery due to a pre-existing health condition in January 2024. Unfortunately, she developed a serious infection in her chest cavity and blood. The culprit bacteria was Pseudomonas aeurginosa, a common organism known to cause serious infections. This infection was difficult to treat and eradicate, causing recurrent blood infections in Ms A. She had to be placed on a prolonged course of intravenous antibiotics and was hospitalised for a significant period of time. Coupled with her pre-existing condition which requires lifelong cardiac care and her complex surgical history, she had two bleak choices – undergo an extremely risky surgery to try to root out the infection or remain on intravenous antibiotics for the indeterminate future. Phage therapy, which the team had developed, when used in combination with antibiotics, served as a promising alternative treatment strategy, with a better patient outcome.
Phages exist everywhere – in bodies of water, soil, even on humans and animals. As they are host-specific, it is necessary to find phages that could precisely target the pseudomonas strains that infected Ms A. The team got started on this hunt, working to match the bacteria against their library of over 100 catalogued phages and searching for more in the environment.
After the bacteria are cultured, phage screening (using phage spot test) was performed. When there is a successful match between phage and bacterium, the phage is extracted for propagation and DNA sequencing to confirm that it is suitable and effective.
Associate Professor Andrea Kwa, Deputy Director, Pharmacy (Research & Innovation), SGH, said, “We isolate and identify the specific phages that target the patient’s unique bacterial strains. For the patient, 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. This prevents further emergence of bacterial resistance and ensures thorough eradication of the culprit bacteria.”
One of the three phages was obtained from the Singapore River. The phage screen, test and production of the safe phage formulation took the team about five months.
The treatment was administered intravenously, and the two-week course treated the infection effectively. Because of phage therapy, Ms A avoided the need for high-risk surgery and was able to move from intravenous to oral antibiotics, which indicates significant improvement in the patient’s condition. Because of this, she finally had her long-term vascular access catheter (a silicone tube placed in her vein) removed as antibiotic administration was no longer required. Her need for hospital visits was greatly reduced, and there was vast improvement in quality of life. She was also able to travel overseas with her young family.
While not new, phage therapy is an emerging field and is considered experimental in most countries. In Singapore, as in other countries where this therapy has been administered, the team had to seek approval from the relevant health authorities including the clinical ethics committee, as well as informed consent from the patient in order to proceed. This thorough process ensures patient safety remains paramount, even as we push the boundaries and explore novel treatments for antibiotic-resistant infections.
Since then, the team has also administered phage therapy to two other patients.
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For media enquiries, please contact:
Candice Lee
Communications Department
Singapore General Hospital
Email: Candice.lee.l.f@sgh.com.sg