Enhancement of mupirocin anti-staphylococcal decolonisation therapy by combination with phages

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Authors

SIVÁKOVÁ Alena BOTKA Tibor VACEK Lukáš TKADLEC Jan VRBSKÝ Jan ŠVAGEROVÁ Zuzana KUČEROVÁ Eliška HERMANOVÁ Laura Claudie OSOWSKI Martin ROVŇÁKOVÁ Kristína PETRÁŠ Petr POLAŠTÍK KLEKNEROVÁ Dominika DVOŘÁČKOVÁ Milada RŮŽIČKA Filip

Year of publication 2025
Type Conference abstract
MU Faculty or unit

Faculty of Medicine

Citation
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Description Staphylococcus aureus is a part of the ESKAPE group of highly virulent pathogens with frequent antibiotic resistance. Its carriage is a proven risk factor requiring eradication. Standard decolonization regimens use nasal administration of mupirocin. Resistance to antimicrobials used (up to 81% for mupirocin) may be the reason for the failure of decolonization treatment. In this study we evaluate the combined administration of mupirocin with the phage 812K1/420 to increase treatment efficacy and prevent the spread of mupirocin resistatance. We collected 324 S. aureus isolates from wounds and 20 Panton-Valentine leukocidin (PVL)-positive S. aureus strains from the National Ref erence Laboratory. The genes encoding PVL were detected in all isolates by specific PCR. Antibiotic susceptibility was determined by the disc diffusion method and phage susceptibility was determined as the ability of the phage to propagate on the analyzed strains by a drop test. The effect of mupirocin-phage combined administration was investigated in S. aureus isolates with different susceptibility to mupirocin by monitor ing growth curves and comparing the surviving cell counts. Cultures were performed in a Tecan Infinite M200 PRO microplate reader and OL was measured (A=850 nm). Statistical significance was tested by ANOVA with Dunnet's post-hoc test with P<0.001. A checkerboard assay was used to evaluate the interactions between mupirocin and the phage used. PVL genes were detected in 17 (5.3%) S. aureus isolates. All PVL-positive S. aureus isolates were susceptible to mupirocin, 22% were MRSA and 11% were resistant to the tested phage. We found that the efficacy of phage was reduced in mupirocin-susceptible strains, with mupi rocin increasing the minimum inhibitory concentration (MIC) of the phage up to 1000-fold, whereas the efficacy of mupirocin was not affected. Importantly, the efficacy of phage was not affected in mupirocin-resistant strains. Simultaneous administration of mupirocin and phage 812K1/420 does not reduce the efficacy of conventional anti-staphylococcal decoloniza tion regimens of mupirocin-susceptible strains. However, the combined administration of mupirocin and phage leads to the eradication of mupi rocin-resistant strains, making decolonization therapy more effective and preventing the spread of mupirocin resistance.
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