Abstract
Aim
Antibiotics have limited activity in the treatment of multidrug-resistant or chronic biofilm-associated infections, in particular when implants cannot be removed. Lytic bacteriophages can rapidly and selectively kill bacteria, and can be combined with antibiotics. However, clinical experience in patients with surgical infections is limited. We investigated the outcome and safety of local application of bacteriophages in addition to antimicrobial therapy.
Method
8 patients (2 female and 6 male) with complex orthopedic and cardiovascular infections were included, in whom standard treatment was not feasible or impossible. The treatment was performed in agreement with the Article 37 of the Declaration of Helsinki. Commercial or individually prepared bacteriophages were provided by ELIAVA Institute in Tbilisi, Georgia. Bacteriophages were applied during surgery and continued through drains placed during surgery three times per day for the following 5–14 days. Follow-up ranged from 1 to 28 months.
Results
Median age was 57 years, range 33–75 years. Two patients were diagnosed with a persistent knee arthrodesis infection, one chronic periprosthetic joint infection (PJI), one cardiovascular implantable electronic device (CIED) infection and four patients with left ventricular assist device (LVAD) infection. The isolated pathogens were multi-drug-resistant Pseudomonas aeruginosa (n=3), methicillin-sensitive Staphylococcus aureus (n=4), methicillin-resistant Staphylococcus aureus (MRSA) (n=1) and methicillin-resistant Staphylococcus epidermidis (MRSE) (n=1). 4 infections were polymicrobial.
5 patients underwent surgical debridement with retention of the implant, 1 patient with PJI underwent the exchange of the prosthesis and one patient with LVAD infection was treated conservatively. All patients received intravenous and oral antibiotic therapy and local application of bacteriophages. At follow-up of 12 month, 5 patients were without signs or symptoms of infection, whereas in one patient with LVAD infection, a relapse was observed with emergence of phage-resistant Pseudomonas aeruginosa. In this patient, no surgical revision was performed.
Conclusions
Bacteriophage therapy may represent a valid additional approach, when standard antimicrobial and surgical treatment is not possible or feasible, including in difficult-to-treat infections. In our case series, 5 of 6 patients were infection free after 1 year. Further studies need to address the optimal bacteriophage administration route, concentration, duration of treatment and combination with antimicrobials.
