<p>Multidrug-resistant (MDR) <i>Acinetobacter baumannii</i> poses a major clinical challenge due to its association with high morbidity and mortality, necessitating alternative treatment strategies. Bacteriophages offer a promising solution; however, their narrow host range limits efficacy against diverse <i>A. baumannii</i> strains. To address this limitation, we isolated five distinct phages (vB_AbaSI_1–5) of the class <i>Caudoviricetes</i>, each exhibiting a narrow host range (2.2%-29.6%) against 135 clinical <i>A. baumannii</i> isolates. Ten phage cocktails (A-J) were formulated and tested for host range expansion and bactericidal activity. Cocktails A, D, and E demonstrated enhanced efficacy, infecting 68 of 135 isolates (50.4%) and statistically significantly outperforming individual phages (<i>p</i> &lt; 0.0001). Among these, cocktail A (comprising phages vB_AbaSI_1, vB_AbaSI_2, and vB_AbaSI_3) exhibited the highest killing efficiency against extensively drug-resistant <i>A. baumannii</i> strain DMST43250, along with superior biofilm inhibition and degradation capabilities. Application of cocktail A completely inhibited biofilm formation within 24&#xa0;h.<i> In vivo</i> efficacy was evaluated using a <i>Galleria mellonella</i> infection model, in which cocktail A improved larval survival to 85.0% on day 1 and 60.0% by day 7, exceeding other cocktails (<i>p</i> &lt; 0.0001). These results highlight cocktail A as a promising candidate for phage therapy targeting <i>A. baumannii</i> infections and associated biofilms.</p>

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Extensive screening of ten bacteriophage cocktails revealed an optimal combination with potent therapeutic activity against Acinetobacter baumannii

  • Thanchanok Sawaengwong,
  • Sujintana Janesomboon,
  • Varintip Lerdsittikul,
  • Veerachat Muangsombut,
  • Siwaporn Prachoochote,
  • Narisara Chantratita,
  • Sunee Korbsrisate,
  • Patoo Withatanung

摘要

Multidrug-resistant (MDR) Acinetobacter baumannii poses a major clinical challenge due to its association with high morbidity and mortality, necessitating alternative treatment strategies. Bacteriophages offer a promising solution; however, their narrow host range limits efficacy against diverse A. baumannii strains. To address this limitation, we isolated five distinct phages (vB_AbaSI_1–5) of the class Caudoviricetes, each exhibiting a narrow host range (2.2%-29.6%) against 135 clinical A. baumannii isolates. Ten phage cocktails (A-J) were formulated and tested for host range expansion and bactericidal activity. Cocktails A, D, and E demonstrated enhanced efficacy, infecting 68 of 135 isolates (50.4%) and statistically significantly outperforming individual phages (p < 0.0001). Among these, cocktail A (comprising phages vB_AbaSI_1, vB_AbaSI_2, and vB_AbaSI_3) exhibited the highest killing efficiency against extensively drug-resistant A. baumannii strain DMST43250, along with superior biofilm inhibition and degradation capabilities. Application of cocktail A completely inhibited biofilm formation within 24 h. In vivo efficacy was evaluated using a Galleria mellonella infection model, in which cocktail A improved larval survival to 85.0% on day 1 and 60.0% by day 7, exceeding other cocktails (p < 0.0001). These results highlight cocktail A as a promising candidate for phage therapy targeting A. baumannii infections and associated biofilms.