Efficacy of Bacteriophages in a Staphylococcus aureus Nondiabetic or Diabetic Foot Infection Murine Model

Abstract

This study investigated the in vivo efficacy of three bacteriophages combined compared with linezolid in two mouse models (nondiabetic and diabetic) of Staphylococcus aureus foot infection. In both models, a single injection of bacteriophages in the hindpaw showed significant antibacterial efficacy. Linezolid was as effective as bacteriophages in nondiabetic animals but ineffective in diabetic animals. These findings further support preclinical and clinical studies for the development of phage therapy.

Keywords: Staphylococcus aureus; bacteriophages; diabetic foot infection; preclinical drug studies.

FIG 1

Pharmacokinetics of an assembly of three bacteriophages after systemic injection (A) of 1 × 10⁹ PFU/mouse or intraarticular injection at the kneecap (B) or in the hindpaw (C) of 10⁸ PFU/mouse. Representation of mean ± SD (n = 5) PFU/ml in different organs or biological fluid at 1, 2, 6, 24, 48, and 72 h. ■, blood; ▲, spleen; ●, kidney; and ♦, liver. Detection threshold, 10 PFU/ml.

FIG 2

Bacterial load (log₁₀ CFU/ml), in hindpaws of nondiabetic BALB/c mice (n = 4/group and time point) after treatment with an assembly of three bacteriophages (1 or 10 MOI), linezolid (25 mg/kg i.p.), and the combination of phages plus linezolid. *, P < 0.05; **, P < 0.01; ***, P < 0.001.

FIG 3

Bacterial load (log₁₀ CFU/ml) in hindpaws of diabetic BALB/c mice (n = 3 or 4/group and time point) after treatment with an assembly of three bacteriophages, linezolid (25 mg/kg oral), and the combination of phages plus linezolid. **, P < 0.01; ***, P < 0.001; ****, P < 0.0001.