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• W2116710752 abstract "ABSTRACT Increasing evidence suggests that colistin monotherapy is suboptimal at currently recommended doses. We hypothesized that front-loading provides an improved dosing strategy for polymyxin antibiotics to maximize killing and minimize total exposure. Here, we utilized an in vitro pharmacodynamic model to examine the impact of front-loaded colistin regimens against a high bacterial density (10 8 CFU/ml) of Pseudomonas aeruginosa . The pharmacokinetics were simulated for patients with hepatic (half-life [ t 1/2 ] of 3.2 h) or renal ( t 1/2 of 14.8 h) disease. Front-loaded regimens ( n = 5) demonstrated improvement in bacterial killing, with reduced overall free drug areas under the concentration-time curve ( f AUC) compared to those with traditional dosing regimens ( n = 14) with various dosing frequencies (every 12 h [q12h] and q24h). In the renal failure simulations, front-loaded regimens at lower exposures ( f AUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens ( f AUC of 268 mg · h/liter), with an ∼97% reduction in the area under the viable count curve over 48 h. In hepatic failure simulations, front-loaded regimens yielded rapid initial killing by up to 7 log 10 within 2 h, but considerable regrowth occurred for both front-loaded and traditional regimens. No regimen eradicated the high bacterial inoculum of P. aeruginosa . The current study, which utilizes an in vitro pharmacodynamic infection model, demonstrates the potential benefits of front-loading strategies for polymyxins simulating differential pharmacokinetics in patients with hepatic and renal failure at a range of doses. Our findings may have important clinical implications, as front-loading polymyxins as a part of a combination regimen may be a viable strategy for aggressive treatment of high-bacterial-burden infections." @default.
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• W2116710752 date "2014-03-01" @default.
• W2116710752 modified "2023-10-17" @default.
• W2116710752 title "New Dosing Strategies for an Old Antibiotic: Pharmacodynamics of Front-Loaded Regimens of Colistin at Simulated Pharmacokinetics in Patients with Kidney or Liver Disease" @default.
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• W2116710752 doi "https://doi.org/10.1128/aac.00327-13" @default.
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