Phage therapy combo to combat antibiotic resistance

A preclinical study led by Monash University has found that using a combination of phages and antibiotics may be far more effective against bacterial infections than using the agents individually. The results, published in the journal EBioMedicine, have wide-ranging implications for the future treatment of antibiotic-resistant bacterial infections.

Phage therapy is the use of bacterial viruses to clear a bacterial infection. In recent years there has been growing interest in the use of phage therapy as a potential treatment to combat antibiotic-resistant infections; however, questions remained around the efficacy of phage therapy as a treatment option.

“This has been obfuscated by the fact that clinical phage therapy is almost always administered alongside antibiotics, making it difficult to determine the efficacy of phage therapy,” said study author Dr Jeremy Barr.

The Monash researchers used a phage-antibiotic combination against the world’s leading antibiotic-resistant superbug, Acinetobacter baumannii. The team had previously shown that phages can kill antibiotic-resistant A. baumannii, but in doing so they found that phage-resistant mutants emerged.

“We found that while A. baumannii rapidly became phage-resistant, in doing so they were also resensitised to the same antibiotics they use to resist,” said lead study author Fernando L Gordillo Altamirano.

“Applying this knowledge, we conducted a preclinical trial using animal models and found that the combined use of phages and antibiotics led to significantly improved treatment outcomes than either antibiotics or phage therapy alone.”

The researchers hypothesised that the success of the combination therapy in vivo was due to the emergence of phage-resistant mutants exhibiting antimicrobial resensitisation, followed by targeted treatment with the resensitised antibiotic. According to Barr, “We have been able to confirm that, even in complex living systems, treatment with our characterised phages can reliably steer bacteria towards a phage-resistant variant that is resensitised to antibiotics.

“We believe further research in the field is likely to lead to the discovery of innovative uses of combination therapies using phages and antibiotics in combination, rather than proposing phages as a substitute to antibiotics.”

Image caption: Colourised scanning electron microscopy image of phage FG02 (orange) infecting Acinetobacter baumannii bacteria (green). Image credit: Denis Korneev.

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