Bacteriophage therapy for a chronic MRSA prosthetic joint infection

This is the case of a 72-year-old man with a chronic methicillin-resistant Staphylococcus aureus prosthetic joint infection. After the third dose of intravenous bacteriophage therapy, an unusual reversible transaminitis led to the discontinuation of bacteriophage therapy. Despite this, the treatment was successful, and the patient’s severe chronic infection was eradicated.

According to the conclusions of this research team, this is the first case of bacteriophage therapy successfully used as an adjuvant therapy to cure chronic MRSA PJI. Two other successful bacteriophage treatments for MSSA and Pseudomonas PJI have been reported [10,11]. A unique aspect of our case is that no chronic suppressive antibiotics were used. Little is known about the optimal duration of treatment or routes of administration in PJI. A longer treatment was planned, but therapy was discontinued when significant transaminitis occurred. Nevertheless, effective sterilization of the patient’s joint and devitalized bone was achieved with IA bacteriophage therapy and 3-day IV bacteriophage therapy, in combination with standard IV antibiotics for 6 weeks. Considering the ability of bacteriophages to self-replicate, only a few days of bacteriophage therapy might be needed as a complement to surgical debridement. Clinical trials are needed to determine an adequate duration of bacteriophage therapy under these conditions [10,11].

So far, surgical debridement has been necessary in all PJI patients successfully treated with bacteriophages [10,11]. This intervention allows for manual biofilm removal, ensures that the prosthesis is salvageable, and permits the instillation of bacteriophages directly onto the biofilm. Local dosing of bacteriophages may be crucial for eliminating biofilm infections, but data beyond case reports are limited [10,11,12]. With repeated IA doses, no adverse events occurred, likely due to limited systemic absorption. Future studies will be needed to determine appropriate routes of administration in PJI.
The most peculiar aspect of our case was the transaminitis that appeared after the third IV dose of bacteriophages. This appeared to be caused by bacteriophage therapy. No other liver function abnormalities were found, and the transaminitis was reversible and not life-threatening. Figure 2 shows the trend of liver function during bacteriophage therapy.

The patient presented with hepatomegaly, but non-alcoholic fatty liver disease was not radiologically demonstrated, and biopsy was postponed. Over 99% of IV bacteriophage therapy is rapidly cleared by the liver and spleen [13,14,15]. This research team’s theory is that underlying steatosis induced hepatic macrophages to trigger a dysregulated local cytokine response when faced with a large number of bacteriophages to clear at the hepatic level. This local reaction could have caused inflammatory changes in hepatocytes, leading to increased AST and ALT. This is supported by studies examining the role of hepatic macrophages in steatosis and, in older studies, in hepatic clearance of bacteriophages [13,14,15]. It is unknown whether mild to moderate elevations of liver enzymes frequently occur after bacteriophage administration. Furthermore, it is unknown whether continued IV bacteriophage administration would have worsened the transaminitis or led to adaptation and resolution. For now, intravenously administered bacteriophages should be used with caution in patients with underlying liver disease, and liver enzymes should be closely monitored. This case is limited because we did not study our patient’s cytokine response to bacteriophage therapy. Future studies should evaluate this response to better understand the normal human cytokine response to bacteriophage therapy.

In summary, salvage of the patient’s prosthesis was not possible due to severe bone erosion. However, we were able to sterilize the patient’s severe chronic MRSA PJI with a single virulent bacteriophage, administered via IA and IV for three days in combination with IV antibiotics. Further studies on PJI are needed to define the optimal duration and mode of phage administration. Bacteriophage therapy has enormous potential for curing PJI, but phase 1 and 2 clinical trials must be conducted.

Translated from source:
https://www.mdpi.com/2079-6382/9/5/241/htm
Salvage Bacteriophage Therapy for a Chronic MRSA Prosthetic Joint Infection
by James B. Doub,*, Vincent Y. Ng, Aaron J. Johnson, Magdalena Slomka, Joseph Fackler, Bri’Anna Horne, Michael J. Brownstein, Matthew Henry,