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Synergy of polymyxi...
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.
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- Olsson, Anna (författare)
- Uppsala universitet,Infektionsmedicin
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- Malmberg, Christer (författare)
- Uppsala universitet,Infektionsmedicin,Institutionen för medicinsk cellbiologi
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- Zhao, Chenyan (författare)
- Uppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap
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- Friberg, Lena (författare)
- Uppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap
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- Nielsen, Elisabet I., 1973- (författare)
- Uppsala universitet,Institutionen för farmaci,Institutionen för farmaceutisk biovetenskap
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- Lagerbäck, Pernilla (författare)
- Uppsala universitet,Infektionsmedicin
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- Tängdén, Thomas (författare)
- Uppsala universitet,Infektionsmedicin
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(creator_code:org_t)
- 2023
- 2023
- Engelska.
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Ingår i: Journal of Antimicrobial Chemotherapy. - 0305-7453 .- 1460-2091.
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
Nyckelord
- Enterobacterales
- carbapenem resistance
- KPC
- OXA-48
- combination therapy
- pharmacokinetics
- pharmacodynamics
- Infektionssjukdomar
- Infectious Diseases
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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