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Activity of polymyx...
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Olsson, AnnaUppsala universitet,Infektionsmedicin
(författare)
Activity of polymyxin B combinations against genetically well-characterised Klebsiella pneumoniae producing NDM-1 and OXA-48-like carbapenemases
- Artikel/kapitelEngelska2023
Förlag, utgivningsår, omfång ...
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Elsevier,2023
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electronicrdacarrier
Nummerbeteckningar
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LIBRIS-ID:oai:DiVA.org:uu-516885
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-516885URI
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https://doi.org/10.1016/j.ijantimicag.2023.106967DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:154192963URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:art swepub-publicationtype
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Background: Combination therapy can enhance the activity of available antibiotics against multidrug-resistant Gram-negative bacteria. This study assessed the effects of polymyxin B combinations against carbapenemase-producing Klebsiella pneumoniae ( K. pneumoniae).Methods: Twenty clinical K. pneumoniae strains producing NDM-1 (n = 8), OXA-48-like (n = 10), or both NDM-1 and OXA-48-like (n = 2) carbapenemases were used. Whole-genome sequencing was applied to detect resistance genes (e.g. encoding antibiotic-degrading enzymes) and sequence alterations influ-encing permeability or efflux. The activity of polymyxin B in combination with aztreonam, fosfomycin, meropenem, minocycline, or rifampicin was investigated in 24-hour time-lapse microscopy experiments. Endpoint samples were spotted on plates with and without polymyxin B at 4 x MIC to assess resistance development. Finally, associations between synergy and bacterial genetic traits were explored.Results: Synergistic and bactericidal effects were observed with polymyxin B in combination with all other antibiotics: aztreonam (11 of 20 strains), fosfomycin (16 of 20), meropenem (10 of 20), minocy-cline (18 of 20), and rifampicin (15 of 20). Synergy was found with polymyxin B in combination with fosfomycin, minocycline, or rifampicin against all nine polymyxin-resistant strains. Wildtype mgrB was associated with polymyxin B and aztreonam synergy (P = 0.0499). An absence of arr-2 and arr-3 was associated with synergy of polymyxin B and rifampicin (P = 0.0260). Emergence of populations with reduced polymyxin B susceptibility was most frequently observed with aztreonam and meropenem.Conclusion: Combinations of polymyxin B and minocycline or rifampicin were most active against the tested NDM-1 and OXA-48-like-producing K. pneumoniae. Biologically plausible genotype-phenotype as-sociations were found. Such information might accelerate the search for promising combinations and guide individualised treatment.
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Allander, LisaUppsala universitet,Infektionsmedicin(Swepub:uu)lisal119
(författare)
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Shams, AydaUppsala universitet,Institutionen för medicinska vetenskaper(Swepub:uu)aydsh857
(författare)
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Al-Farsi, HissaKarolinska Inst, Dept Lab Med, Div Clin Microbiol, Stockholm, Sweden.
(författare)
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Lagerbäck, PernillaUppsala universitet,Infektionsmedicin(Swepub:uu)pla05791
(författare)
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Tängdén, ThomasUppsala universitet,Infektionsmedicin(Swepub:uu)thota437
(författare)
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Uppsala universitetInfektionsmedicin
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:International Journal of Antimicrobial Agents: Elsevier62:50924-85791872-7913
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