{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T20:47:19Z","timestamp":1791492439431,"version":"4.3.4"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2025,5,31]],"date-time":"2025-05-31T00:00:00Z","timestamp":1748649600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013209","name":"Hellenic Foundation for Research and Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013209","id-type":"DOI","asserted-by":"publisher"}]},{"name":"2nd Call for H.F.R.I. Research Projects to support Faculty Members & Researchers","award":["4211"],"award-info":[{"award-number":["4211"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,7,1]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Therapeutic options for MDR carbapenemase-producing Klebsiella pneumoniae (CRKP) are limited. We therefore assessed the in vitro activity of five antibiotics from different classes in combination with lytic bacteriophages (phages) against MDR CRKP isolates.<\/jats:p>\n <\/jats:sec>\n \n Material and methods<\/jats:title>\n A total of 15 non-repetitive, well-characterized MDR CRKP isolates and four phages belonging to the Podoviridae family were used in chequerboard assays with amikacin, meropenem, ciprofloxacin, colistin and ceftazidime\/avibactam. The spectrophotometrically determined MIC of drugs and phages alone and in combination were used to calculate the fractional inhibitory concentration index (FICi). The clinical relevance was assessed based on the MIC reductions at clinically achievable concentrations and below the corresponding susceptibility breakpoints. Emergence of resistance was studied in growth curves and time\u2013kill experiments.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Synergy was found for ciprofloxacin in 6\/15 (40%) isolates, meropenem in 10\/15 (67%), ceftazidime\/avibactam in 11\/15 (73%), colistin in 8\/15 (53%) and amikacin in 9\/15 (60%) with all four phages against host bacteria. The synergistic interactions were strong as the FICi were 0.01\u20130.35 reducing the MICs (&gt;90% growth inhibition) to clinically achievable concentrations for 87%\u2013100% of strains, except ciprofloxacin. Reversal of phenotypic resistance was observed for amikacin, meropenem, colistin and ceftazidime\/avibactam in 100%, 53%, 89% and 80% of isolates, respectively. No emergence of resistance was found for isolates with low level resistance to amikacin (M\u0399C 64\u2005mg\/L).<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The phage\u2013antibiotic combinations were synergistic against more than half of the isolates for all antibiotics except ciprofloxacin reversing resistance in most strains particularly with amikacin.<\/jats:p>\n <\/jats:sec>","DOI":"10.1093\/jac\/dkaf163","type":"journal-article","created":{"date-parts":[[2025,5,21]],"date-time":"2025-05-21T08:56:29Z","timestamp":1747817789000},"page":"1997-2006","source":"Crossref","is-referenced-by-count":9,"title":["Reversal of phenotypic resistance in multi-drug resistant carbapenemase-producing\n K. pneumoniae<\/i>\n clinical isolates due to\n in vitro<\/i>\n synergistic interactions between bacteriophages and antibiotics at clinically achievable concentrations"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1934-8691","authenticated-orcid":false,"given":"Paschalis","family":"Paranos","sequence":"first","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-1007","authenticated-orcid":false,"given":"Maria","family":"Siopi","sequence":"additional","affiliation":[{"name":"Clinical Microbiology Laboratory, Attikon University Hospital, Medical School, National and Kapodistrian University of Athens , Athens ,","place":["Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleni","family":"Papanikolaou","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Faculty of Biology, National and Kapodistrian University of Athens , Athens 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