Phage therapy of staphylococcal chronic osteomyelitis in experimental animal model

Abstract

Background & objectives: Methicillin resistant Staphylococcus aureus (MRSA) are the commonest cause of osteomyelitis. The aim of this study was to evaluate the role of an alternative therapy i.e. application of S. aureus specific bacteriophages in cases of osteomyelitis caused by MRSA in animal model.

Methods: Twenty two rabbits were included in this study. The first two rabbits were used to test the safety of phage cocktail while the remaining 20 rabbits were divided into three groups; group A (n=4) to assess the establishment of osteomyelitis; group B (n=4) osteomyelitis developed but therapy started only after six weeks; and group C (n=12) osteomyelitis developed and therapy started after three weeks. Groups B and C rabbits were treated with four doses of cocktail of seven virulent bacteriophages at the interval of 48 h. Comparison between three groups was made on the basis of observation of clinical, radiological, microbiological, and histopathological examinations.

Results: Experimental group rabbits recovered from the illness in the subsequent two weeks of the therapy. Appetite and activity of the rabbits improved, local oedema, erythema and induration subsided. There were minimal changes associated with osteomyelitis in X-ray and histopathology also showed no signs of infection with new bone formation. Control B group rabbits also recovered well from the infection.

Interpretation & conclusions: The present study shows a potential of phage therapy to treat difficult infections caused by multidrug resistant bacteria.

Fig. 1

Exposure and inoculation of S. aureus through drill hole (a) and (b) in distal femur and frank pus discharge (c).

Fig. 2

Pus culture showing positive result in 2^nd (a) and 5^th (b) week, negative result in 7^th week (c) in group B rabbits.

Fig. 3

X-ray of group C rabbits showing sclerosis and osteolysis at 3^rd week (a), periosteal reaction with sequestrum formation (b1) and arthritis (b2) at 5^th week, similar features but decrease in sclerosis and ostelysis at 7^th week (c).

Fig. 4

Histopathological slides of group C rabbits showing minimal inflammation at 3^rd week (a) and no inflammation with new formation at 6^th week (b). Stain H & E, magnification 10x.