Intranasal Bacteriophage Shows Promise Against S. Aureus Chronic Rhinosinusitis

By Will Boggs MD

June 27, 2019

NEW YORK (Reuters Health) - Intranasal bacteriophage therapy appears to be safe and well tolerated and has promising preliminary efficacy in patients with chronic rhinosinusitis (CRS) due to Staphylococcus aureus, according to results from a phase 1 first-in-human, single-arm trial.

Bacteriophage therapy was proposed as an antibacterial treatment more than a century ago, but the development of effective antimicrobials outpaced it. The emergence of antibiotic-resistant strains of bacteria has triggered renewed interest.

Dr. Peter-John Wormald of the University of Adelaide, in Australia and colleagues tested twice-daily intranasal irrigation with AB-SAO1, a mixture of three natural lytic phages capable of killing a wide range of clinical S. aureus strains, in their study of nine adults with recalcitrant CRS.

All nine participants reported that the irrigations were well-tolerated, and the six treatment-emergent adverse effects reported by six participants were all of mild severity and resolved by the end of the study.

All patients had reduction in S. aureus growth, and two had negative cultures after treatment, the researchers report in JAMA Otolaryngology-Head and Neck Surgery, online June 20.

Bacteriophage treatment had an inconsistent effect on symptom scores, but there was a consistent trend toward improvement in endoscopic scores.

Four patients with persistence of symptoms after treatment who elected not to receive antibacterial treatment after cessation of the study showed a continuing trend toward further improvement in all outcome measures at three-month follow-up.

"The results of our phase 1 study will guide a phase 2 trial in which a randomized, double-blind, placebo-controlled group will be used to evaluate efficacy," the researchers note.

Dr. Joanna Szaleniec of Jagiellonian University Medical College, in Krakow, Poland, who recently reviewed the potential of phage therapy for treating CRS, told Reuters Health by email, "Phage therapy can be a promising alternative for patients with sinonasal infections who do not benefit from antibiotic therapy. The safety of phage preparations seems to be well established. Its efficacy requires further investigation."

"We have to keep in mind that the role of bacteria in CRS is not clear," cautioned Dr. Szaleniec, who was not involved in the trial. "Antimicrobial treatment is indicated primarily in acute bacterial exacerbations of CRS. In patients without signs of bacterial exacerbations, the bacteria that constantly dwell in the sinuses may actually have no impact on the course of the disease."

"Therefore, antimicrobial treatment (including phage therapy) can alleviate the symptoms of exacerbation, but may not cause improvement in the patients' underlying chronic condition," Dr. Szaleniec said. "Better understanding of bacterial dysbiosis in patients with CRS would be required to manipulate the sinonasal microbiome and achieve permanent improvement."

AmpliPhi Biosciences Corporation supported the study. One of the authors was employed by the company.

Dr. Wormald did not respond to a request for comments.


JAMA Otolaryngol Head Neck Surg 2019.