In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections

Odou, M.F.; Muller, Claudette; Calvet, L.; Dubreuil, L.

doi:10.1093/jac/dkm019

Cited by 32 publications

(21 citation statements)

References 18 publications

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“…It has a low potential for organisms to develop resistance and has not shown cross-resistance to other antimicrobial classes. Retapamulin has been shown to be similar in efficacy to topical fusidic acid and to oral cephalexin for treating impetigo or infected traumatic lesions [40][41][42], but there are no data on use of this agent for chronic wounds.…”

Section: What Types Of Topical Antimicrobials Are Available?mentioning

confidence: 99%

Topical Antimicrobial Therapy for Treating Chronic Wounds

2009

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Various agents have been applied topically to treat infected wounds for millennia, but their proper role remains unclear. Topical therapy affords many potential advantages but also has disadvantages. Opinions differ on which clinical signs define wound infection and on whether quantitative microbiological studies are useful. Clinically infected wounds usually require systemic antibiotic therapy, whereas clinically uninfected wounds that are healing as expected do not require antimicrobials. There is controversy over how to treat poorly healing wounds with "secondary" signs suggesting infection; these may benefit from topical antimicrobial agents. Some evidence supports using topical agents for malodorous or burn wounds. Meta-analyses and systematic reviews suggest there are few proven indications for topical antimicrobials. Use of a newer, relatively nontoxic antiseptic (eg, cadexomer iodine or silver dressings) is preferable to use of topical antibiotics, especially agents that are available for systemic use. We provide clinically relevant information on currently available topical antimicrobial agents.

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Section: What Types Of Topical Antimicrobials Are Available?mentioning

confidence: 99%

Topical Antimicrobial Therapy for Treating Chronic Wounds

2009

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“…A novel semisynthetic pleuromutilin, retapamulin {mutilin 14-(exo-8-methyl-8-azabicyclo [3.2.1]oct-3-yl-sulfanyl)-acetate}, is active against Staphylococcus aureus and Streptococcus pyogenes (39,47) and is the first pleuromutilin derivative which has been formulated as a topical antibacterial agent for treating human skin infections (14,38,41). In 2007, the Food and Drug Administration and the European Commission approved a new topical retapamulin ointment for the treatment of impetigo and infected small lacerations, abrasions, or sutured wounds.…”

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confidence: 99%

Establishing Molecular Tools for Genetic Manipulation of the Pleuromutilin-Producing FungusClitopilus passeckerianus

Kilaru

Collins

Hartley

et al. 2009

Appl Environ Microbiol

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We describe efficient polyethylene glycol (PEG)-mediated and Agrobacterium-mediated transformation systems for a pharmaceutically important basidiomycete fungus, Clitopilus passeckerianus, which produces pleuromutilin, a diterpene antibiotic. Three dominant selectable marker systems based on hygromycin, phleomycin, and carboxin selection were used to study the feasibility of PEG-mediated transformation of C. passeckerianus. The PEG-mediated transformation of C. passeckerianus protoplasts was successful and generated hygromycinresistant transformants more efficiently than either phleomycin or carboxin resistance. Agrobacterium-mediated transformation with plasmid pBGgHg containing hph gene under the control of the Agaricus bisporus gpdII promoter led to hygromycin-resistant colonies and was successful when homogenized mycelium and fruiting body gill tissue were used as starting material. Southern blot analysis of transformants revealed the apparently random integration of the transforming DNA to be predominantly multiple copies for the PEG-mediated system and a single copy for the Agrobacterium-mediated system within the genome. C. passeckerianus actin and tubulin promoters were amplified from genomic DNA and proved successful in driving green fluorescent protein and DsRed expression in C. passeckerianus, but only when constructs contained a 5 intron, demonstrating that the presence of an intron is prerequisite for efficient transgene expression. The feasibility of RNA interference-mediated gene silencing was investigated using gfp as a target gene easily scored in C. passeckerianus. Upon transformation of gfp antisense constructs into a highly fluorescent strain, transformants were recovered that exhibited either reduced or undetectable fluorescence. This was confirmed by Northern blotting showing depletion of the target mRNA levels. This demonstrated that gene silencing is a suitable tool for modulating gene expression in C. passeckerianus. The molecular tools developed in this study should facilitate studies aimed at gene isolation or characterization in this pharmaceutically important species.

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“…Retapamulin demonstrated favorable in vitro activity against anaerobes, including Propionibacterium species associated with acnes vulgaris, Fusobacterium species, and other anaerobic Gram-positive cocci, 14,17,24 and respiratory tract pathogens, including Haemophilus infl uenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. 16 The in vitro activities of retapamulin against common pathogens associated with uncomplicated SSSIs reported in published studies correspond well with those found in the global surveillance program.…”

Section: In Vitro Activity Of Retapamulin: Published Studiesmentioning

confidence: 99%

“…13 A recent addition to available topical antibiotics is retapamulin, a novel semisynthetic pleuromutilin antibiotic that has a unique mode of action and potent in vitro activity against a wide range of pathogens, particularly Gram-positive cocci. [14][15][16][17] An ointment formulation of 1% retapamulin received regulatory approval from the US Food and Drug Administration for the treatment of impetigo and from the European Medicines Agency in 2007 for the short-term treatment of the following superfi cial skin infections: impetigo and infected small lacerations, abrasions, and sutured wounds. Retapamulin is the fi rst new prescription topical antibiotic in more than 20 years.…”

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confidence: 99%

Topical retapamulin in the management of infected traumatic skin lesions

Shawar

Scangarella-Oman

Dalessandro³

et al. 2008

TCRM

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Abstract:Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifi cally designed for use as a topical agent. The unique mode of action by which retapamulin selectively inhibits bacterial protein synthesis differentiates it from other nonpleuromutilin antibacterial agents that target the ribosome or ribosomal factors, minimizing the potential for target-specifi c crossresistance with other antibacterial classes in current use. In vitro studies show that retapamulin has high potency against the Gram-positive bacteria (Staphylococcus aureus, Streptococcus pyogenes, and coagulase-negative staphylococci) commonly found in skin and skin-structure infections (SSSIs), including S. aureus strains with resistance to agents such as macrolides, fusidic acid, or mupirocin, and other less common organisms associated with SSSIs, anaerobes, and common respiratory tract pathogens. Clinical studies have shown that twice-daily topical retapamulin for 5 days is comparable to 10 days of oral cephalexin in the treatment of secondarily infected traumatic lesions. A 1% concentration of retapamulin ointment has been approved for clinical use as an easily applied treatment with a short, convenient dosing regimen for impetigo. Given the novel mode of action, low potential for cross-resistance with established antibacterial agents, and high in vitro potency against many bacterial pathogens commonly recovered from SSSIs, retapamulin is a valuable enhancement over existing therapeutic options.

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In vitro activity against anaerobes of retapamulin, a new topical antibiotic for treatment of skin infections

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Cited by 32 publications

References 18 publications

Topical Antimicrobial Therapy for Treating Chronic Wounds

Topical Antimicrobial Therapy for Treating Chronic Wounds

Establishing Molecular Tools for Genetic Manipulation of the Pleuromutilin-Producing FungusClitopilus passeckerianus

Topical retapamulin in the management of infected traumatic skin lesions

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