Key result
Linezolid plus bacteriophage reduces kidney bacterial load ~99% vs monotherapy in infected mice.
Why the study?
Given growing antibiotic resistance in Staphylococcus aureus infections, evaluating the synergistic effect of bacteriophages combined with antibiotics is a promising approach.
Does linezolid combined with bacteriophage reduce bacterial load in a mouse model of systemic Staphylococcus aureus infection?
Does linezolid combined with bacteriophage reduce bacterial load in a mouse model of systemic Staphylococcus aureus infection?
Effect estimate: Decreased by 2-3 orders of magnitude
p-value: p=0.0028
The combination of linezolid and bacteriophage synergistically reduces bacterial load in a mouse model of systemic S. aureus infection, suggesting a promising strategy to enhance efficacy and potentially reduce antibiotic doses.
Phage-linezolid synergy in murine systemic staphylococcal infection warrants human trials; animal data leaves open clinical translation.
Staphylococcus aureus is the causative agent of a wide range of infections, including severe systemic diseases, which is often multidrug resistant. Given the growing overall antibiotic resistance, a promising approach to treating staphylococcal infections is administration of bacteriophages, especially in combination with antibiotics. This study aimed to evaluate the synergistic effect of linezolid and bacteriophage vB_SauM-515A1 in combating a systemic infection in BALB/c mice. Using 36 animals, we established the optimal way of administration and the infecting dose of the microorganism (5 × 108 CFU/mouse intravenously), and identified the threshold concentrations of antimicrobial agents for monotherapy. The evaluation was based on the revealed contamination of internal organs (kidneys, spleen) and blood. To learn the etiotropic effect of linezolid (10 mg/kg animal weight) combined with the phage (2 × 107 PFU/mouse), we worked with a control group and a test group, 12 mice in each; 2, 8, 18, and 24 hours after infection, the former received the drug only, the latter — the investigated combination. Combined therapy had a more pronounced effect, decreasing the bacterial load in the kidneys by two to three orders of magnitude compared with monotherapy on the first day of treatment. Thus, the combined use of linezolid and bacteriophages is promising for the treatment of infections caused by S. aureus, and may increase the effectiveness of treatment and reduce the risk of side effects of high-dose antibiotics.
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Kornienko et al. (2024) studied Systemic staphylococcal infection (n=84). Linezolid and bacteriophage vB_SauM-515A1 vs. Linezolid monotherapy, bacteriophage monotherapy, or saline control was evaluated on Bacterial load in the kidneys (log CFU/organ/ml) (Decreased by 2-3 orders of magnitude, p=0.0028). Combined therapy with linezolid and bacteriophage vB_SauM-515A1 decreased the bacterial load in the kidneys of S. aureus-infected mice by two to three orders of magnitude compared with monotherapy.
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