{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T02:11:56Z","timestamp":1792116716216,"version":"4.4.0"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Phage therapy is one of the most promising alternatives to antibiotics as we face global antibiotic resistance crisis. However, the pharmacokinetics (PK) and pharmacodynamics (PD) of phage therapy are largely unknown. In the present study, we aimed to evaluate the PK\/PD of a locally isolated virulent novel \u00f8Kp_Pokalde_002 (<jats:italic>Podoviridae<\/jats:italic>, C1 morphotype) that infects carbapenem-resistant<jats:italic>Klebsiella pneumoniae<\/jats:italic>(Kp56) using oral and intraperitoneal (IP) route in a mouse model. The result showed that the \u00f8Kp_Pokalde_002 rapidly distributed into the systemic circulation within an hour<jats:italic>via<\/jats:italic>both oral and IP routes. A higher concentration of phage in plasma was found after 4\u00a0h (2.3 x 10<jats:sup>5<\/jats:sup>PFU\/ml) and 8\u00a0h (7.3 x 10<jats:sup>4<\/jats:sup>PFU\/ml) of administration through IP and oral route, respectively. The phage titer significantly decreased in the blood and other tissues, liver, kidneys, and spleen after 24\u00a0h and completely cleared after 72\u00a0h of administration. In the Kp56 infection model, the bacterial count significantly decreased in the blood and other organs by 4\u20137 log<jats:sub>10<\/jats:sub>CFU\/ml after 24\u00a0h of \u00f8Kp_Pokalde_002 administration. Elimination half-life of \u00f8Kp_Pokalde_002 was relatively shorter in the presence of host-bacteria Kp56 compared to phage only, suggesting rapid clearance of phage in the presence of susceptible host. Further, administration of the \u00f8Kp_Pokalde_002 alone in healthy mice (<jats:italic>via<\/jats:italic>IP or oral) did not stimulate pro-inflammatory cytokines (TNF-\u03b1 and IL-6). Also, treatment with \u00f8Kp_Pokalde_002 resulted in a significant reduction of pro-inflammatory cytokines (TNF-\u03b1 and IL-6) caused by bacterial infection, thereby reducing the tissue inflammation. In conclusion, the \u00f8Kp_Pokalde_002 possess good PK\/PD properties and can be considered as a potent therapeutic candidate for future phage therapy in carbapenem-resistant<jats:italic>K. pneumoniae<\/jats:italic>infections.<\/jats:p>","DOI":"10.3389\/fcimb.2021.684704","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T10:51:31Z","timestamp":1629111091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":59,"title":["Pharmacokinetics and Pharmacodynamics of a Novel Virulent Klebsiella Phage Kp_Pokalde_002 in a Mouse Model"],"prefix":"10.3389","volume":"11","author":[{"given":"Gunaraj","family":"Dhungana","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Nepal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhav","family":"Regmi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajani","family":"Malla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"10771","DOI":"10.1073\/pnas.1305923110","article-title":"Bacteriophage Adhering to Mucus Provide a non-Host-Derived Immunity","volume":"110","author":"Barr","year":"2013","journal-title":"Proc. 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