The Treatment of Gram-negative Bacillary Infections with Colistin

Fr, Fekety; Ps, Norman; Le, Cluff

doi:10.7326/0003-4819-57-2-214

Cited by 85 publications

(17 citation statements)

References 8 publications

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“…In the early years of their use, polymyxin-associated neurotoxicity occurred in patients with an incidence as high as 27% following parenteral administration [3,41]. However, recent retrospective clinical studies have not shown neurotoxicity to be a major concern [42,43].…”

Section: Toxicodynamics Of Polymyxinsmentioning

confidence: 99%

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

Tran

Velkov

Nation

et al. 2016

International Journal of Antimicrobial Agents

154

131

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The polymyxin antibiotics [colistin and polymyxin B (PMB)] are increasingly used as a last-line option for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria. Despite having similar structures and antibacterial activity in vitro, the two clinically available polymyxins have very different pharmacological properties, as colistin (polymyxin E) is intravenously administered to patients in the form of an inactive prodrug colistin methanesulphonate (sodium). This review will discuss recent progress in the pharmacokinetics/pharmacodynamics and toxicity of colistin and PMB, the factors that affect their pharmacological profiles, and the challenges for the effective use of both polymyxins. Strategies are proposed for optimising their clinical utility based upon the recent pharmacological studies in vitro, in animals and patients. In the ‘bad bugs, no drugs’ era, polymyxins are a critically important component of the antibiotic armamentarium against difficult-to-treat Gram-negative ‘superbugs’. Rational approaches to the use of polymyxins must be pursued to increase their effectiveness and to minimise resistance and toxicity.

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Section: Toxicodynamics Of Polymyxinsmentioning

confidence: 99%

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

Tran

Velkov

Nation

et al. 2016

International Journal of Antimicrobial Agents

154

131

View full text Add to dashboard Cite

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“…Neurotoxicity (manifested as dizziness, weakness, peripheral paresthesia, vertigo, confusion, ataxia, or neuromuscular blockade) of systemically used colistin is potentially severe but occurs rarely according to the earlier literature: milder symptoms, such as the most frequently reported paresthesias, were reported in up to 27% of patients 89,90. As far as severe neurotoxic symptoms are concerned, at least eight cases were published between 1964 and 1973 correlating the intramuscular administration of polymyxins with the development of episodes of respiratory apnea (reviewed by Falagas et al24).…”

Section: Toxicity Issuesmentioning

confidence: 99%

Colistimethate sodium for the treatment of chronic pulmonary infection in cystic fibrosis: an evidence-based review of its place in therapy

Koerner-Rettberg¹,

Ballmann²

2014

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Chronic bacterial respiratory-tract infections are a major driving force in the pathogenesis of cystic fibrosis (CF) lung disease and promote chronic lung-function decline, destruction, and progression to respiratory failure at a premature age. Gram-negative bacteria colonizing the airways in CF are a major problem in CF therapy due to their tendency to develop a high degree of resistance to antibiotic agents over time. Pseudomonas aeruginosa is the dominating bacterial strain infecting the CF lung from early childhood on, and multiresistant strains frequently develop after years of therapy. Colistin has been used for treating pulmonary bacterial infections in CF for decades due to its very good Gram-negative activity. However, drawbacks include concerns regarding toxicity when being applied systemically, and the lack of approval for application by inhalation in the USA for many years. Other antibiotic substances for systemic use are available with good to excellent Gram-negative and anti-Pseudomonas activity, while there are only three substances approved for inhalation use in the treatment of chronic pulmonary infection with proven benefit in CF. The emergence of multiresistant strains leaving nearly no antibiotic substance as a treatment option, the limited number of antibiotics with high activity against P. aeruginosa, the concerns about increasing the risk of antibiotic resistance by continuous antibiotic therapy, the development of new drug formulations and drug-delivery devices, and, finally, the differing treatment strategies used in CF centers call for defining the place of this “old” drug, colistimethate, in today’s CF therapy. This article reviews the available evidence to reflect on the place of colistimethate sodium in the therapy of chronic pulmonary infection in CF.

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“…Moreover, the histological abnormality was not found in olfactory bulbs. Renal insufficiency represents a major adverse effect of the use of polymyxins by intramuscular [41], [42] or intravenous [43] administration. Histological findings of polymyxin-induced renal damage usually involve focal irregular dilatation of tubules, epithelial and polymorphonuclear cell cast formation, as well as degeneration and regeneration of epithelial cells.…”

Section: Resultsmentioning

confidence: 99%

“…Polymyxins were used in intravenous therapy, but during 1950s and 1960s, concerns arose concerning adverse effects (nephrotoxicity, ototoxicity, and neuromuscular blockade) associated with their use [41]–[43]. However, polymyxins were brought back to clinical use because of the gradual increase in the infection incidence worldwide, due to the emergence of MDR gram-negative pathogens in hospitalized patients with considerable morbidity and mortality, as well as the unavailability of newer antimicrobial agents to combat these infections [22], [23].…”

Section: Discussionmentioning

confidence: 99%

Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice

et al. 2013

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There is currently an urgent need to develop safe and effective adjuvants for enhancing vaccine-induced antigen-specific immune responses. We demonstrate here that intranasal immunization with clinically used polypeptide antibiotics, polymyxin B (PMB) and colistin (CL), along with ovalbumin (OVA), increases OVA-specific humoral immune responses in a dose-dependently manner at both mucosal and systemic compartments. Enhanced immunity by boosting was found to persist during 8 months of observation. Moreover, mice intranasally immunized with OVA plus various doses of PMB or CL showed neither inflammatory responses in the nasal cavity and olfactory bulbs nor renal damages, compared to those given OVA alone. These data suggest that polymyxins may serve as novel and safe mucosal adjuvants to induce humoral immune responses. The polymyxin adjuvanticity was found to be independent of endotoxins liberated by its bactericidal activity, as indicated by similar enhancing effects of PMB in lipopolysaccharide (LPS)-hyporesponsive and LPS-susceptible mice. However, despite the presence of preexisting anti-PMB antibodies, we observed no reduction in the adjuvant function of polymyxins when they were given intranasally. Furthermore, the titers of OVA-specific Abs in mice intranasally immunized with OVA plus PMB or CL were significantly higher than those in mice administered with polymyxin analogues, such as polymyxin B nonapeptide and colistin methanesulfonate. The levels of released β-hexosaminidase and histamine in mast cell culture supernatants stimulated by PMB or CL were also significantly higher than those stimulated by their analogues. These results suggest that both the hydrophobic carbon chain and hydrophilic cationic cyclic peptide contribute to the mucosal adjuvanticity of PMB and CL.

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The Treatment of Gram-negative Bacillary Infections with Colistin

Cited by 85 publications

References 8 publications

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

Colistimethate sodium for the treatment of chronic pulmonary infection in cystic fibrosis: an evidence-based review of its place in therapy

Polymyxins as Novel and Safe Mucosal Adjuvants to Induce Humoral Immune Responses in Mice

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