The Journal of Infectious Diseases · 2003 · 261 citations · 42 references
Life SciencesInfectious DiseasesMicrobiologyAntimicrobial ResistanceMedical MicrobiologySepsisAntibacterial AgentsAntibiotic ResistanceAntimicrobial TherapyBacterial InfectionsBacterial PathogenesisBacteriophage GeneticsAntibacterial ImmunityAntibacterial ToxicityAntibiotic Resistance GenesBacteriophage TherapyIntraperitoneal AdministrationMethicillin-resistant Staphylococcus Aureus BacteremiaMicrobial ToxinsPlasmid Host Range
The protective effects of bacteriophages were assessed against experimental Staphylococcus aureus infection in mice. Of the S. aureus phages isolated in the study, phi MR11 was representatively used for all testing, because its host range was the most broad and it carries no genes for known toxins or antibiotic resistance. Intraperitoneal injections (8 x 10(8) cells) of S. aureus, including methicillin-resistant bacteria, caused bacteremia and eventual death in mice. In contrast, subsequent intraperitoneal administration of purified phi MR11 (MOI > or = 0.1) suppressed S. aureus-induced lethality. This lifesaving effect coincided with the rapid appearance of phi MR11 in the circulation, which remained at substantial levels until the bacteria were eradicated. Inoculation with high-dose phi MR11 alone produced no adverse effects attributable to the phage. These results uphold the efficacy of phage therapy against pernicious S. aureus infections in humans and suggest that phi MR11 may be a potential prototype for gene-modified, advanced therapeutic S. aureus phages.
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Daniel Nelson, Lawrence D. Loomis, Vincent A. Fischetti · Proceedings of the National Academy of Sciences · 2001 · 587 citations · Full text