{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T22:59:59Z","timestamp":1788303599819,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T00:00:00Z","timestamp":1643068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Fosfomycin has emerged as a very useful antimicrobial in management of extremely drug resistant (XDR) and pan drug resistant (PDR) Klebsiella pneumoniae. In this study, we assessed in-vitro synergy of colistin sparing combinations of fosfomycin (FOS) with meropenem (MEM), tigecycline (TGC) and amikacin (AK) against XDR and PDR Klebsiella pneumoniae. Method: Non-replicate fully characterised 18 clinical isolates of K. pneumoniae (15 XDR and 3 PDR strains) were subjected to in-vitro synergy testing by checkerboard and time kill assay. Combinations tested were FOS-MEM, FOS-TGC and FOS-AK with glucose-6-phosphate being incorporated in all runs.WGS was carried out on the Illumina next-generation sequencing platform. Results: FOS-MEM and FOS-AK both demonstrated excellent synergy against all PDRs and all but one XDR. Synergy led to lowering of MICs to susceptible breakpoints. FOS-TGC demonstrated antagonism. MLST-231 K. pneumoniae predominated (14), followed by ST-395 (3) and ST147 (1). Majority harboured OXA-232 (n = 15), while n = 2 carried NDM-1 type and n = 1 co-carried NDM-5 + OXA-232. Mortality was high in both ST-231 (57.1%) and ST-395 (66.6%). Synergy was observed despite widespread presence of resistance markers against aminoglycosides [aph(3\u2032)-Ic, aacA4, and rmtf], beta-lactams [blaSHV-11, blaTEM-1b, blaCTX-M-15, and blaOXA-232], fosfomycin [fosA6 and fosA5] and presence of porin proteins OmpK37, OmpA and K. pneumoniae antibiotic efflux pumps Kpn F, H, G, and E. Conclusion: FOS + MEM and FOS + AK are excellent colistin sparing combinations against ST 231, ST-395 and ST-147 XDR and PDR K. pneumoniae. FOS with fewer side effects than colistin, excellent tissue distribution and minimal side effects may be recommended in combination with meropenem.<\/jats:p>","DOI":"10.3390\/antibiotics11020153","type":"journal-article","created":{"date-parts":[[2022,1,25]],"date-time":"2022-01-25T20:44:33Z","timestamp":1643143473000},"page":"153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Assessment of In-Vitro Synergy of Fosfomycin with Meropenem, Amikacin and Tigecycline in Whole Genome Sequenced Extended and Pan Drug Resistant Klebsiella Pneumoniae: Exploring A Colistin Sparing Protocol"],"prefix":"10.3390","volume":"11","author":[{"given":"Manawr","family":"AL-Quraini","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meher","family":"Rizvi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zaaima","family":"AL-Jabri","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4594-852X","authenticated-orcid":false,"given":"Hiba","family":"Sami","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Jawahar Lal Nehru Medical College, AMU, Aligarh 202002, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muna","family":"AL-Muzahmi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zakariya","family":"AL-Muharrmi","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neelam","family":"Taneja","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology, Post Graduate Institute of Medical Education and Research, Chandigarh 160012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5126-1276","authenticated-orcid":false,"given":"Ibrahim","family":"AL-Busaidi","sequence":"additional","affiliation":[{"name":"Infectious Diseases Unit, Sultan Qaboos University Hospital, Muscat 123, Oman"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajeev","family":"Soman","sequence":"additional","affiliation":[{"name":"Jupiter Hospital Pune, Deenanath Mangeshkar Hospital Pune, Bharati University, Pune 411045, India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1111\/j.1469-0691.2011.03570.x","article-title":"Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: An international expert proposal for interim standard definitions for acquired resistance","volume":"18","author":"Magiorakos","year":"2012","journal-title":"Clin. 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