Table 2.

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

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.	[151]
• 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.	[126]
• 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.	[152]
• 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.	[153]
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.	[154]