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Synergy of polymyxi...
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Olsson, AnnaUppsala universitet,Infektionsmedicin,Institutionen för medicinska vetenskaper
(författare)
Synergy of polymyxin B and minocycline against KPC-3- and OXA-48-producing Klebsiella pneumoniae in dynamic time-kill experiments : agreement with in silico predictions.
- Artikel/kapitelEngelska2023
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2023
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Oxford University Press,2023
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LIBRIS-ID:oai:DiVA.org:uu-519780
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-519780URI
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https://doi.org/10.1093/jac/dkad394DOI
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https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-457612URI
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Språk:engelska
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Sammanfattning på:engelska
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Ämneskategori:ref swepub-contenttype
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Ämneskategori:art swepub-publicationtype
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OBJECTIVES: Combination therapy is often used for carbapenem-resistant Gram-negative bacteria. We previously demonstrated synergy of polymyxin B and minocycline against carbapenem-resistant Klebsiella pneumoniae in static time-kill experiments and developed an in silico pharmacokinetic/pharmacodynamic (PK/PD) model. The present study assessed the synergistic potential of this antibiotic combination in dynamic experiments.METHODS: Two clinical K. pneumoniae isolates producing KPC-3 and OXA-48 (polymyxin B MICs 0.5 and 8 mg/L, and minocycline MICs 1 and 8 mg/L, respectively) were included. Activities of the single drugs and the combination were assessed in 72 h dynamic time-kill experiments mimicking patient pharmacokinetics. Population analysis was performed every 12 h using plates containing antibiotics at 4× and 8× MIC. WGS was applied to reveal resistance genes and mutations.RESULTS: The combination showed synergistic and bactericidal effects against the KPC-3-producing strain from 12 h onwards. Subpopulations with decreased susceptibility to polymyxin B were frequently detected after single-drug exposures but not with the combination. Against the OXA-48-producing strain, synergy was observed between 4 and 8 h and was followed by regrowth. Subpopulations with decreased susceptibility to polymyxin B and minocycline were detected throughout experiments. For both strains, the observed antibacterial activities showed overall agreement with the in silico predictions.CONCLUSIONS: Polymyxin B and minocycline in combination showed synergistic effects, mainly against the KPC-3-producing K. pneumoniae. The agreement between the experimental results and in silico predictions supports the use of PK/PD models based on static time-kill data to predict the activity of antibiotic combinations at dynamic drug concentrations.
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Lagerbäck, PernillaUppsala universitet,Infektionsmedicin,Institutionen för medicinska vetenskaper(Swepub:uu)pla05791
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Tängdén, ThomasUppsala universitet,Infektionsmedicin,Institutionen för medicinska vetenskaper(Swepub:uu)thota437
(författare)
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Uppsala universitetInfektionsmedicin
(creator_code:org_t)
Sammanhörande titlar
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Ingår i:Journal of Antimicrobial Chemotherapy: Oxford University Press0305-74531460-2091
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