ArticleAntimicrobial agents and chemotherapy2014
New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 36 citations in OpenAlex.
- A novel role for colistin as an efflux pump inhibitor in multidrug-resistant Klebsiella pneumoniae.Scientific reports · 2025Article
- A novel antibiotic combination of linezolid and polymyxin B octapeptide PBOP against clinical Pseudomonas aeruginosa strains.Annals of clinical microbiology and antimicrobials · 2022Article
- Dose Optimization of Colistin: A Systematic Review.Antibiotics (Basel, Switzerland) · 2021Review
- Dosage Individualization of Linezolid: Precision Dosing of Linezolid To Optimize Efficacy and Minimize Toxicity.Antimicrobial agents and chemotherapy · 2021Article
- Evaluation Strategies for Triple-Drug Combinations against Carbapenemase-Producing Klebsiella Pneumoniae in an In Vitro Hollow-Fiber Infection Model.Clinical pharmacology and therapeutics · 2021Article
- Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against polymyxin-resistant mcr-1-harbouring Escherichia coli.The Journal of antimicrobial chemotherapy · 2017Article
- Review
- Development of new polymyxin derivatives for multi-drug resistant Gram-negative infections.The Journal of antibiotics · 2017Review
- Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae.Antimicrobial agents and chemotherapy · 2017Article
- Combinatorial pharmacodynamics of polymyxin B and tigecycline against heteroresistant Acinetobacter baumannii.International journal of antimicrobial agents · 2016Article
- Paradoxical Effect of Polymyxin B: High Drug Exposure Amplifies Resistance in Acinetobacter baumannii.Antimicrobial agents and chemotherapy · 2016Article
- In vitro activity of fosfomycin in combination with colistin against clinical isolates of carbapenem-resistant Pseudomas aeruginosa.The Journal of antibiotics · 2015Article
- Antimicrobial dosing in critically ill patients with sepsis-induced acute kidney injury.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2015Article
- Fulminant endocarditis and disseminated infection caused by carbapenem-resistant Acinetobacter baumannii in a renal-pancreas transplant recipient.Transplant infectious disease : an official journal of the Transplantation Society · 2015Article
- New dosing strategies for an old antibiotic: pharmacodynamics of front-loaded regimens of colistin at simulated pharmacokinetics in patients with kidney or liver disease.Antimicrobial agents and chemotherapy · 2014Article
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
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 [t1/2] of 3.2 h) or renal (t1/2 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 (fAUC) 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 (fAUC of 143 mg · h/liter) obtained killing activity similar to that of traditional regimens (fAUC 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 log10 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.
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