Selection of retapamulin, a novel pleuromutilin for topical use.
(2006)
Journal - Antimicrobial agents and chemotherapy (United States )
Abstract :
The in vitro activity of retapamulin was determined and compared to that of topical and community antibiotics. The MIC(90)s of retapamulin against Staphylococcus aureus and Streptococcus pyogenes were 0.12 microg/ml and 0.016 microg/ml, respectively. Retapamulin has a low propensity to select resistance and produces an in vitro postantibiotic effect.
| ISSN : | 0066-4804 |
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| Mesh Heading : | Anti-Infective Agents, Local Bacteria Bicyclo Compounds, Heterocyclic Diterpenes Drug Resistance, Bacterial Haemophilus influenzae Humans Microbial Sensitivity Tests Moraxella (Branhamella) catarrhalis Mupirocin Skin Diseases, Bacterial Staphylococcus Streptococcus pharmacology drug effects drug effects pharmacology microbiology drug effects drug effects |
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| Mesh Heading Relevant : | pharmacology drug effects pharmacology |
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Use of the surgical wound infection model to determine the efficacious dosing regimen of retapamulin, a novel topical antibiotic.
(2006)
Journal - Antimicrobial agents and chemotherapy (United States )
Abstract :
The effect of topically applied retapamulin ointment was evaluated using various dosing regimens in the Staphylococcus aureus and Streptococcus pyogenes wound infection model. Retapamulin (1%, wt/wt) was efficacious using twice-daily (b.i.d.) applications for 4 or 5 days. These data underpinned the decision to evaluate 1% retapamulin b.i.d. in clinical trials.
| ISSN : | 0066-4804 |
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| Mesh Heading : | Administration, Topical Animals Anti-Bacterial Agents Anti-Infective Agents, Local Bicyclo Compounds, Heterocyclic Colony Count, Microbial Drug Resistance, Bacterial Methicillin Resistance Mice Mupirocin Ointments Staphylococcal Infections Staphylococcus aureus Surgical Wound Infection administration & dosage therapeutic use administration & dosage therapeutic use drug therapy microbiology drug effects microbiology |
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| Mesh Heading Relevant : | administration & dosage therapeutic use administration & dosage therapeutic use drug therapy |
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Genetic Characterization of Vga ABC Proteins Conferring Reduced Susceptibility to Pleuromutilins in Staphylococcus aureus
(2008)
Journal - Antimicrobial Agents and Chemotherapy
Abstract :
Retapamulin MICs of =2 µg/ml were noted for 6 of 5,676 S. aureus recent clinical isolates evaluated. The ABC proteins VgaAv and VgaA were found to be responsible for the reduced susceptibility to pleuromutilins exhibited by these six isolates.
Stepwise Exposure of Staphylococcus aureus to Pleuromutilins Is Associated with Stepwise Acquisition of Mutations in rplC and Minimally Affects Susceptibility to Retapamulin
(2007)
Journal - Antimicrobial Agents and Chemotherapy
Abstract :
To assess their effects on susceptibility to retapamulin in Staphylococcus aureus, first-, second-, and third-step mutants with elevated MICs to tiamulin and other investigational pleuromutilin compounds were isolated and characterized through exposure to high drug concentrations. All first- and second-step mutations were in rplC, encoding ribosomal protein L3. Most third-step mutants acquired a third mutation in rplC. While first- and second-step mutations did cause an elevation in tiamulin and retapamulin MICs, a significant decrease in activity was not seen until a third mutation was acquired. All third-step mutants exhibited severe growth defects, and faster-growing variants arose at a high frequency from most isolates. These faster-growing variants were found to be more susceptible to pleuromutilins. In the case of a mutant with three alterations in rplC, the fast-growing variants acquired an additional mutation in rplC. In the case of fast-growing variants of isolates with two mutations in rplC and at least one mutation at an unmapped locus, one of the two rplC mutations reverted to wild type. These data indicate that mutations in rplC that lead to pleuromutilin resistance have a direct, negative effect on fitness. While reduction in activity of retapamulin against S. aureus can be seen through mutations in rplC, it is likely that target-specific resistance to retapamulin will be slow to emerge due to the need for three mutations for a significant effect on activity and the fitness cost of each mutational step.