Phage-antibiotic combination: a possible approach to combatting multidrug-resistant Klebsiella pneumoniae

Abstract

Multidrug-resistant Klebsiella pneumoniae is a major global health concern due to its role in severe hospital-acquired infections and resistance to multiple antibiotics. As conventional antibiotics lose effectiveness, bacteriophage (phage) therapy offers a promising alternative. This study assessed phage therapy alone and combined with antibiotics against multidrug-resistant K. pneumoniae using the time-kill assay. A total of 48 clinical isolates were collected and identified as K. pneumoniae. According to their antibiotic susceptibility, 91.7% (n = 44) of the tested isolates were multidrug-resistant. Sewage samples were processed to isolate a phage-coded Kp25, which showed lytic activity against 17 isolates and remained stable within a temperature range of 40–90 °C and a pH range of 3–11. The taxonomic classification of the phage was made clear by the findings of the genomic analysis, which is Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes; Drexlerviridae; Webervirus; Webervirus domnhall. Phage combination with sub-MIC of levofloxacin and meropenem showed potential antibacterial activity, so that complete in vitro bacterial eradication was achieved starting from 4 h incubation until the end of the incubation period. However, phage combination with sub-MIC of gentamicin showed weak antibacterial activity. These findings highlight the phage combination with levofloxacin and meropenem as an effective strategy against multidrug-resistant K. pneumoniae.