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Table 2 Recent studies demonstrating the therapeutic success of phage therapy in treatment of bone and joint infections

From: Novel therapeutic interventions towards improved management of septic arthritis

Outline of Study

Major Findings

Reference

Therapeutic efficacy of cocktail of five phages against S. aureus given intraperitoneally at a dose of 108 PFU/ml in a rat model of joint infection (alone as well as along with vancomycin)

• Phage treatment alone led to 5-fold reduction in bacterial load in the peri-implant tissue.

• When given in combination with vancomycin, 6.2 fold reduction occurred.

• 22.5 fold decrease in bacterial burden in the joint tissue unlike sham treated animals.

• Phage treated animals showed marked reduction in swelling and joint inflammation.

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• Therapeutic efficacy of MRSA phage MR-5 given single as well as co-therapy with linezolid in resolving MRSA mediated implant infection in mouse model of post arthroplasty joint infection.

• Phage MR-5 alone as well as mixed with linezolid was encapsulated in biodegradable HPMC gel and coated onto K-wires.

• Coated and uncoated K-wires inserted into the mice femur followed by MRSA inoculation.

• Dual Hydrogel based system exhibited release of both agents i.e phage and linezolid in a slow sustained manner in the joint tissue

• Combination therapy showed synergistic effects.

• Highest decrease in bacterial burden, improvement in joint mobility and lowered cytokine levels seen in combination group.

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• To evaluate efficacy of S. aureus specific bacteriophage cocktail formulations against MRSA employing rabbit model of osteomyelitis.

• Phage therapy initiated 3-6 weeks post development of experimental osteomyelitis.

• Test animals received four repeated doses of seven MRSA phages in a cocktail mix given at the interval of 48 h.

• Test rabbits recovered from the infection within two weeks with marked decline in local oedema, erythema and induration.

• Phage treated group showed new bone formation and improved histopathology.

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• Clinical case study of salvage phage therapy in a 72 year old male with a chronic MRSA prosthetic joint infection.

• Infection persisted even after two DAIR procedures.

• Patient administered three doses of 2.7 × 109 PFU through i.v route along with daptomycin.

• Phages were able to sterilize the patient’s severe chronic MRSA joint infection with a single virulent bacteriophage given i.v for three days giving negative cultures.

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Clinical case:

• 42-year old man with multidrug-resistant left tibial infection was positive for multidrug resistant strains of Klebsiella pneumoniae and Acinetobacter baumannii.

• Patient received combination therapy of bacteriophage (intravenous bacteriophage therapy at 107 PFU/mL titers) and antibiotics.

• Within days of phage administration, the patient showed improved wound healing, decrease in the chronic bone pain.

• Negative bacterial cultures obtained for both the causative bacteria and patients’ leg was thus saved from amputation surgery.

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