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Evaluating Polymyxin B-Based Combinations against Carbapenem-Resistant Escherichia coli in Time-Kill Studies and in a Hollow-Fiber Infection Model.
Cai, Yiying; Lim, Tze-Peng; Teo, Jocelyn Qi-Min; Sasikala, Suranthran; Chan, Eric Chun Yong; Hong, Yan Jun; Lee, Winnie; Tan, Thean Yen; Tan, Thuan Tong; Koh, Tse Hsien; Hsu, Li Yang; Kwa, Andrea L.
Afiliación
  • Cai Y; Department of Pharmacy, Singapore General Hospital, Singapore.
  • Lim TP; Department of Pharmacy, National University of Singapore, Singapore.
  • Teo JQ; Department of Pharmacy, Singapore General Hospital, Singapore.
  • Sasikala S; Duke-NUS Medical School, Office of Clinical Sciences, Singapore.
  • Chan EC; Department of Pharmacy, Singapore General Hospital, Singapore.
  • Hong YJ; Department of Pharmacy, Singapore General Hospital, Singapore.
  • Lee W; Department of Pharmacy, National University of Singapore, Singapore.
  • Tan TY; Department of Pharmacy, National University of Singapore, Singapore.
  • Tan TT; Department of Pharmacy, Singapore General Hospital, Singapore.
  • Koh TH; Department of Laboratory Medicine, Changi General Hospital, Singapore.
  • Hsu LY; Department of Infectious Diseases, Singapore General Hospital, Singapore.
  • Kwa AL; Department of Pathology, Singapore General Hospital, Singapore.
Article en En | MEDLINE | ID: mdl-27795375
ABSTRACT
Polymyxin B-based combinations have emerged as a mainstay treatment against carbapenem-resistant Escherichia coli (CREC). We investigated the activity of polymyxin B-based two-antibiotic combinations against CREC using time-kill studies (TKS) and validated the findings in a hollow-fiber infection model (HFIM). TKS were conducted using 5 clinical CREC strains at 5 log10 CFU/ml against 10 polymyxin B-based two-antibiotic combinations at maximum clinically achievable concentrations. HFIMs simulating dosing regimens with polymyxin B (30,000U/kg/day) and tigecycline (100 mg every 12 h) alone and in combination were conducted against two CREC strains at 5 log10 CFU/ml over 120 h. Emergence of resistance was quantified using antibiotic-containing media. Phenotypic characterization (growth rate and stability of resistant phenotypes) of the resistant isolates was performed. All five CREC strains harbored carbapenemases. Polymyxin B and tigecycline MICs ranged from 0.5 mg/liter to 2 mg/liter and from 0.25 mg/liter to 8 mg/liter, respectively. All antibiotics alone did not have bactericidal activity at 24 h in the TKS, except for polymyxin B against two strains. In combination TKS, only polymyxin B plus tigecycline demonstrated both bactericidal activity and synergy in two out of five strains. In the HFIM, polymyxin B alone was bactericidal against both CREC strains before regrowth was observed at 8 h. Phenotypically stable polymyxin B-resistant mutants were observed for both strains, with a reduced growth rate observed in one strain. Tigecycline alone resulted in a slow reduction in bacterial counts. Polymyxin B plus tigecycline resulted in rapid and sustained bactericidal killing up to 120 h. Polymyxin B plus tigecycline is a promising combination against CREC. The clinical relevance of our results warrants further investigations.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polimixina B / Carbapenémicos / Escherichia coli / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: Antimicrob Agents Chemother Año: 2017 Tipo del documento: Article País de afiliación: Singapur

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Polimixina B / Carbapenémicos / Escherichia coli / Antibacterianos Tipo de estudio: Prognostic_studies Idioma: En Revista: Antimicrob Agents Chemother Año: 2017 Tipo del documento: Article País de afiliación: Singapur