Use of colistin in treating multi-resistant Gram-negative organisms in a specialised burns unit

Ganapathy, Hemalatha; Pal, Saurabh; Teare, Louise; Dziewulski, Peter

doi:10.1016/j.burns.2009.07.010

Cited by 28 publications

(7 citation statements)

References 37 publications

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“…Doses for patients with renal insufficiency must be adjusted because colistin is primarily excreted by the kidneys, and elevated blood levels of the drug may further impair renal function. However, renal function impairment should not be attributed solely to colistin toxicity because other factors, such as the development of septic shock and multiorgan failure, may also make a significant contribution [23].…”

Section: Discussionmentioning

confidence: 99%

Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea

et al. 2011

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Section: Discussionmentioning

confidence: 99%

Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea

et al. 2011

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“…The analysis of bacterial counts in the presence of colistin sulfate was interesting and showed that bacterial recovery occurred earlier than the shortest currently recommended dosing interval for colistin (31,32), demonstrating the clinical benefit that these models may offer. In contrast, with the dextrin-colistin conjugates, the recovery of bacterial counts was significantly delayed, presumably due to the sustained release of colistin from dextrincolistin conjugates by ␣-amylase.…”

Section: Discussionmentioning

confidence: 99%

Development and Validation of an In Vitro Pharmacokinetic/Pharmacodynamic Model To Test the Antibacterial Efficacy of Antibiotic Polymer Conjugates

Azzopardi

Ferguson

Thomas

2015

Antimicrob Agents Chemother

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bThis study describes the use of a novel, two-compartment, static dialysis bag model to study the release, diffusion, and antibacterial activity of a novel, bioresponsive dextrin-colistin polymer conjugate against multidrug resistant (MDR) wild-type Acinetobacter baumannii. In this model, colistin sulfate, at its MIC, produced a rapid and extensive drop in viable bacterial counts (<2 log 10 CFU/ml at 4 h); however, a marked recovery was observed thereafter, with regrowth equivalent to that of control by 48 h. In contrast, dextrin-colistin conjugate, at its MIC, suppressed bacterial growth for up to 48 h, with 3 log 10 CFU/ml lower bacterial counts after 48 h than those of controls. Doubling the concentration of dextrin-colistin conjugate (to 2؋ MIC) led to an initial bacterial killing of 3 log 10 CFU/ml at 8 h, with a similar regrowth profile to 1؋ MIC treatment thereafter. The addition of colistin sulfate (1؋ MIC) to dextrin-colistin conjugate (1؋ MIC) resulted in undetectable bacterial counts after 4 h, followed by suppressed bacterial growth (3.5 log 10 CFU/ml lower than that of control at 48 h). Incubation of dextrin-colistin conjugates with infected wound exudate from a series of burn patients (n ‫؍‬ 6) revealed an increasing concentration of unmasked colistin in the outer compartment (OC) over time (up to 86.3% of the initial dose at 48 h), confirming that colistin would be liberated from the conjugate by endogenous ␣-amylase within the wound environment. These studies confirm the utility of this model system to simulate the pharmacokinetics of colistin formation in humans administered dextrin-colistin conjugates and further supports the development of antibiotic polymer conjugates in the treatment of MDR infections. In an attempt to meet the challenge of the global epidemic of antibiotic-resistant infections, treatment strategies are increasingly employing nanomedicine-based approaches, which have been used in the treatment of a number of human diseases with considerable success (1, 2). The adoption of these approaches as antimicrobial therapies has seen the preclinical development of novel agents, including antibiotic-bearing nanoparticles, liposomes, dendrimers, and polymer therapeutics (3, 4). These agents may offer potential benefits over conventional systemic delivery in minimizing toxicity and overcoming drug resistance by affording selective targeting of systemically delivered antibiotics to sites of infection and inflammation, thus maximizing local bioavailability of the chemotherapeutic agent (3, 5). The employment of polymer therapeutics, in which an antibiotic is covalently attached to a water-soluble polymer, may afford a number of important practical advantages, including increased solubility and bioavailability, decreased toxicity, and a chemically modifiable controlled-release system that can be truly customized (2, 4, 6).In this respect, we recently described a nanoantibiotic polymer therapeutic, based on dextrin conjugated to colistin, whereby colistin is controllably released from the co...

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“…CMS at daily doses of 160,000 IU/kg (maximum 5.3 MIU) in four divided doses in pediatric burn patients with mean body surface area involvement of 38% and MDR Pseudomonas and Acinetobactr species was safe and effective in an Argentinian study [82]. Colistin treatment for multidrug resistance Gram-negative bacteria including P. aeruginosa and A. baumannii resulted in 69-98% favorable outcome [82][83][84]. In the largest study on 118 pediatric burn patients who received CMS at daily dose of 146,000 ± 30,000 IU/kg in 2-3 divided doses, nephrotoxicity occurred in 16% of the patients, however, colistin-treated patients had higher mortality rate compared with patients who received piperacillin/tazobactam plus vancomycin.…”

Section: Burn Patientsmentioning

confidence: 97%

Colistin: efficacy and safety in different populations

Shahbazi

Dashti‐Khavidaki

2015

Expert Review of Clinical Pharmacology

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This article reviews mechanisms, incidences, risk factors and preventive modalities of colistin toxicity as well as colistin use in special populations and through special routes. All clinical studies that examined the pharmacokinetic/pharmacodynamic, efficacy and side effects of colistin in the management of multidrug-resistant organisms in different patient population including pediatrics, adults, obese, critically ill, burn or cancer patients with any route of drug administration were considered. Compared with older recommended doses, current dosing approach improves cure rate without significant increase in the rate of colistin-induced nephrotoxicity. Efficacy and safety of high doses of colistin should be considered in the future studies. Also comparing efficacy and safety of different doses of aerosolized colistin and defining the appropriate dose in different populations is another open area of future researches.

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Use of colistin in treating multi-resistant Gram-negative organisms in a specialised burns unit

Cited by 28 publications

References 37 publications

Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea

Use of parenteral colistin for the treatment of multiresistant Gram-negative organisms in major burn patients in South Korea

Development and Validation of an In Vitro Pharmacokinetic/Pharmacodynamic Model To Test the Antibacterial Efficacy of Antibiotic Polymer Conjugates

Colistin: efficacy and safety in different populations

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