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However, the factors that govern bacteriophage pharmacokinetics in vivo remain poorly understood. Here, we have examined the contribution of neutrophils, the most abundant phagocytes in the body, to the pharmacokinetics of i.v. administered bacteriophage in uninfected mice. A single dose of LPS-5, a bacteriophage recently used in human clinical trials to treat drug-resistant\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    , was administered i.v. to both immunocompetent BALB\/c and neutropenic CD1 mice. Phage concentrations were assessed in peripheral blood and spleen at 0.25, 1, 2, 4, 8, 12, and 24 hours after administration by plaque assay and qPCR. We observed that the phage clearance was only minimally affected by neutropenia. Indeed, the half-lives of phages in blood in BALB\/c and CD1 mice were 3.45 and 3.66 hours, respectively. These data suggest that neutrophil-mediated phagocytosis is not a major determinant of phage clearance. Conversely, we observed a substantial discrepancy in circulating phage levels over time when measured by qPCR versus plaque assay, suggesting that significant inactivation of circulating phages occurs over time. These data indicate that alternative factors, but not neutrophils, inactivate i.v. administered phages.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.181309","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T09:49:08Z","timestamp":1729849748000},"source":"Crossref","is-referenced-by-count":25,"title":["The contribution of neutrophils to bacteriophage clearance and pharmacokinetics in vivo"],"prefix":"10.1172","volume":"9","author":[{"given":"Arne","family":"Echterhof","sequence":"first","affiliation":[{"name":"Division of Infectious Diseases and Geographic Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA."},{"name":"Institute of Medical Microbiology, University Hospital of Muenster, Muenster, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tejas","family":"Dharmaraj","sequence":"additional","affiliation":[{"name":"Division of Infectious Diseases and Geographic 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