Evaluation of bacteriophage cocktail on Urinary Tract Infection caused by colistin-resistant Klebsiella pneumoniae in mice model
Abstract
OBJECTIVE
The colistin-resistant Klebsiella pneumoniae causes complicated Urinary Tract Infections (UTIs). Of them, 73% of strains of K. pneumoniae formed moderate to strong biofilm. Multidrug-resistant (MDR)/Pandrug-resistant (PDR) bacteria causing UTIs are very challenging to conventional antibiotic therapy. However, bacteriophages may be a promising alternative as they easily disrupt the biofilm and act on receptors unrelated to antibiotic resistance mechanisms. This preclinical study evaluated the efficacy of a phage cocktail with different routes and dosages (in quantity and frequency) to eradicate the K. pneumoniae-associated UTI in the mice model.
METHODS
The three lytic phages with the broadest spectrum activity (ΦKpnBHU1, ΦKpnBHU2, and ΦKpnBHU3) were meticulously characterized using SEM and sequencing. The cocktails were administered to mice through urethral, rectal, subcutaneous, and oral routes after establishing the UTI with 1 × 108 colony-forming unit/mouse (CFU/mouse) of K. pneumoniae (KpnBHU09) resistant to both the drugs carbapenem and colistin. The efficacy of different routes with varying dosages and frequency of administration was thoroughly optimized.
RESULTS
We observed that two doses of a phage cocktail containing 1 × 105 Plaque-Forming Unit (PFU/mouse) and a single dose of 1 × 109 PFU/mouse per urethra could eradicate KpnBHU09. Intriguingly, the noninvasive administration through oral and rectal routes required higher concentration and many dosages of…
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