Experimental phage therapy against haematogenous multi-drug resistant Staphylococcus aureus pneumonia in mice

BACKGROUND Community-acquired haematogenous Staphylococcus aureus pneumonia is a rare infection, though it can be acquired nosocomially. Currently, antibiotics used against S. aureus pneumonia have shown reduced efficacy. Thus, there is need for an alternative therapy against multidrug-resistant S. aureus (MDRSA) strains in the community. OBJECTIVE We sought to determine the efficacy of environmentally-obtained S. aureus lytic phage against haematogenous MDRSA pneumonia in mice. METHODS Phages and MDRSA were isolated from sewage samples collected within Nairobi County, Kenya. Isolated S. aureus bacteria were screened for resistance against ceftazidime, oxacillin, vancomycin, netilmicin, gentamicin, erythromycin, trimethroprim-sulfamethoxazole and cefuroxime. Thirty BALB/c mice aged six to eight weeks were randomly assigned into three groups: the MDRSA-infection group (n = 20), the phage-infection group (n = 5) and the non-infection group (n = 5). Mice were infected with either MDRSA or phage (108 CFU/mL) and treated after 72 hours with a single dose of clindamycin (8 mg/kg/bwt) or 108 PFU/mL of phage or a combination therapy (clindamycin and phage). The efficacy of phage, clindamycin or clindamycin with phage combination was determined using resolution of lung pathology and bacterial load in lung homogenates. RESULTS The viable MDRSA count was 0.5 ± 0.2 log10 CFU/gm in the phage-treated group, 4.4 ± 0.2 log10 CFU/gm in the clindamycin-treated group and 4.0 ± 0.2 log10 CFU/gm in the combination-treated group. The efficacy of phage therapy was significantly different from other therapeutic modes (p = 0 < 0.0001). Histology showed that the mice treated with phage did not develop pneumonia. CONCLUSION Phage therapy is effective against haematogenous MDRSA infection. Thus, it can be explored as an alternative treatment method.