Staphylococcal PJI can be difficult to eradicate given its propensity to develop biofilms.

Endolysins are bacteriophage-derived hydrolases with rapid bactericidal activity andanti-biofilm activity.

LYSG101 (formerly ClyO) is an investigational anti-staphylococcal endolysin designedfor local intra-articular delivery.

We report the first-in-human intra-articular use of LYSG101 in two patients who hadexhausted standard surgical, antimicrobial, and prior bacteriophage options.

Two patients with chronic total knee arthroplasty PJI received ultrasound-guided intra-articular LYSG101 injections under single-patient expanded-access investigational protocols.

Both had persistent infection despite multiple surgeries, prolonged antimicrobials, and prior bacteriophage therapy; amputation was the only remaining standard option.

Serial clinical assessments (including analgesic use), inflammatory markers, synovial leukocyte counts, and cultures were used toevaluate safety and treatment response.

Adverse events were monitored and reported. Multiply recurrent methicillin-resistant Staphylococcus epidermidis(MRSE) PJI after seven prior surgical procedures.

• Initial arthroplasty > 2-stage exchange > 2-stage exchange > DAIR x2 >DAIR + intra-articular and intravenous lytic phage

• Three ascending intra-articular LYSG101 doses over three consecutive days (dose escalation protocol); no local or systemic adverse events.

• Rapid improvement after two doses with near-complete pain resolution and discontinuation of daily analgesics.

• Synovial culture became negative at day 30 before recurrence 50days later consistent with persistent chronic biofilm-associatedinfection.

• Repeat LYSG101 treatment with intensified dosing schedule paired ith intensified antimicrobials with dalbavancin and rifampin:

• Week 1: Doses 1-5 given once every 24 hours

• Week 2: Doses 6-8 given once every 48 hours

• Week 3: Dose 9

• Week 7: Dose 10

• Week 11: Dose 11

• Week 15: Dose 12

• Chronic Staphylococcus lugdunensisPJI with four draining sinustracts in the setting of post-surgical lymphedema and no remainingsurgical options.

• DAIR > 2-stage exchange > intra-articular and intravenous lytic phage

• Four intra-articular doses of LYSG101 were administered over twoweeks; treatment was generally well tolerated.

• A transient self-limited systemic reaction followed the first dose anddid not recur.

• Infection parameters remained microbiologically positive during early follow-up.

   

  • Microbiologic clearance and rapid symptom improvement in one patientsupport biologic activity of locally delivered endolysin therapy despite chronicity of biofilm-associated infection.

   

  • Findings support prospective investigation as an adjunctive strategy for device-associated musculoskeletal infection.

• • First-in-human local LYSG101 therapy was feasible and generally well tolerated in patients lacking standard limb-salvage options.