Abstract
Background
Bacteriophages are natural viruses of interest in the field of PJI. A paper previously reported the PhagoDAIR procedure (use of phages during DAIR) in three patients with PJI for whom explantation was not desirable. As the need to isolate the pathogen before surgery to perform phage susceptibility testing is a strong hindrance for the development of this procedure, we developed post-operative phage injections using ultrasound, in patients infected with S. aureus and/or P. aeruginosa who were eligible for the PhagoDAIR procedure, but for whom phages were not available at the time of surgery.
Materials/Methods
We performed a single center, exploratory, prospective cohort study including patients with knee PJI who received phage therapy with ultrasound after performance of a DAIR or a partial prosthesis exchange. All patients had PJI requiring conservative surgery and suppressive antimicrobial therapy (SAT) as salvage procedure. Each case was discussed in multidisciplinary meetings in agreement with French health authority, based on the clinical presentation, and the phage susceptibility testing. The cocktail of highly concentrate active phages (5 mL; about 10e9 PFU/mL) was extemporaneous prepared and administered three times directly into the joint using sonography (1 injection per week during 3 weeks) during the postoperative period, before switching antibiotics to SAT.
Results
Seven patients received phages under sonography after the DAIR, and one after a partial exchange (mean age 71 years). All had resection prosthesis or constrained knee prosthesis. Among these seven patients, three were infected with S. aureus (including one MRSA), two were infected with P. aeruginosa (one was a multidrug-resistant isolate), one was infected with both S. aureus and P. aeruginosa and the last one was infected with MRSA, S. epidermidis and Corynebacterium spp.. All patients received a cocktail of active phages provided by Pherecydes Pharma targeting S. aureus or P. aeruginosa. No adverse event was recorded during or after the local injections. All patients were switched to SAT after a primary postoperative antimicrobial therapy of three months. Under SAT, the patient with S. epidermidis co-infection developed a relapse due to the S. epidermidis. With a mean follow-up of 13 months after surgery (from 9 to 24 months), the outcome was favorable for all patients without any sign of infection; none of them had abnormal pain, joint effusion or loosening.
Conclusions
Postoperative administration of phages using sonography is a potentially useful procedure in patients with complex PJI for whom a conservative approach is desirable.