retapamulin and Skin-Diseases--Bacterial

Retapamulin is a new topical pleuromutilin antibiotic for the treatment of skin and skin-structure infections, including impetigo. In vitro studies indicate that retapamulin has a unique mode of action that minimizes the potential for target-specific cross-resistance with other antibacterials and a limited potential for resistance development. Its spectrum of activity includes the most likely causative pathogens Staphylococcus aureus and Streptococcus pyogenes. In the Global Surveillance Program, retapamulin was highly active in vitro, including against strains of S. aureus resistant to methicillin, mupirocin or fusidic acid. In clinical studies, retapamulin was noninferior to fusidic acid and oral cefalexin, achieving per-pathogen success rates of 86-99%. Topical retapamulin has a good safety profile and is associated with high patient compliance.

Topics: Administration, Cutaneous; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Drug Resistance, Bacterial; Global Health; Humans; Microbial Sensitivity Tests; Ointments; Population Surveillance; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcal Infections; Streptococcus pyogenes; Treatment Outcome

Topical retapamulin (Altabax, Altargo) is the first pleuromutilin antibacterial approved for the treatment of uncomplicated superficial skin infections caused by Staphylococcus aureus (excluding meticillin-resistant S. aureus [MRSA]) and Streptococcus pyogenes in patients aged > or = 9 months. In the EU, retapamulin is indicated for use in patients with impetigo or with infected small lacerations, abrasions or sutured wounds (without abscesses); in the US, it is indicated for use in patients with impetigo. Retapamulin has a novel site of action on bacterial ribosomes. In clinical trials in patients with impetigo, topical retapamulin 1% ointment twice daily for 5 days (the approved regimen) was superior to placebo; treatment with retapamulin was noninferior to that with topical fusidic acid. In patients with secondarily infected traumatic lesions, treatment with retapamulin was noninferior to that with oral cefalexin, although the efficacy of retapamulin was reduced in patients with MRSA infections or superficial abscesses. Retapamulin was well tolerated in both paediatric and adult patients, and the majority of adverse events were of mild to moderate severity. Thus, the introduction of topical retapamulin 1% ointment extends the treatment options available in the management of impetigo and uncomplicated secondarily infected traumatic lesions.

Topics: Administration, Cutaneous; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Humans; Impetigo; Skin Diseases, Bacterial; Streptococcal Infections; Treatment Outcome

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Drug Resistance, Bacterial; Humans; Protein Synthesis Inhibitors; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Streptococcal Infections; Treatment Outcome

Retapamulin, the first pleuromutilin antimicrobial agent approved for the topical treatment of skin infections in humans, was tested against 987 clinical isolates representing 30 species and/or resistance groups. MICs were determined along with disk diffusion zone diameters using a 2-microg disk. Population distribution and MIC versus disk zone diameter scattergrams were analyzed to determine microbiological MIC cutoff values and inhibition zone correlates. Minimum bactericidal concentrations were performed on a smaller subset of key species. The retapamulin MIC(90) against 234 Staphylococcus aureus isolates and 110 coagulase-negative staphylococci was 0.12 microg/ml. Retapamulin MIC(90)s ranged from 0.03 to 0.06 microg/ml against beta-hemolytic streptococci including 102 Streptococcus pyogenes, 103 Streptococcus agalactiae, 59 group C Streptococcus, and 71 group G Streptococcus isolates. The MIC(90) against 55 viridans group streptococci was 0.25 microg/ml. Retapamulin had very little activity against 151 gram-negative bacilli and most of the Enterococcus species tested. Based on the data from this study, for staphylococci, MICs of or=2 microg/ml with corresponding disk diffusion values of >or=20 mm, 17 to 19 mm, and or=15 mm can be proposed for susceptible-only microbiological cutoffs.

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Bridged Bicyclo Compounds, Heterocyclic; Disk Diffusion Antimicrobial Tests; Diterpenes; Drug Resistance, Bacterial; Enterococcus; Gram-Negative Bacteria; Humans; In Vitro Techniques; Microbial Sensitivity Tests; Mupirocin; Skin Diseases, Bacterial; Staphylococcal Skin Infections; Staphylococcus aureus; Streptococcus

Last year, we concluded that topical fusidic acid should be first-line treatment for impetigo. Since then, retapamulin ointment (Altargo - GlaxoSmithKline), a new antibacterial, has been licensed in the European Union as a short-term treatment for impetigo and infected small lacerations, abrasions or sutured wounds in people aged 9 months or above. Advertisements claim that the product "treats localised impetigo in just 5 days"; by comparison, the British National Formulary (BNF) advises a 7-day course of fusidic acid. Here we consider the place of retapamulin in impetigo and its other licensed indications.

Topics: Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Humans; Impetigo; Ointments; Randomized Controlled Trials as Topic; Skin Diseases, Bacterial; Treatment Outcome; Wound Infection

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.

Topics: Anti-Infective Agents, Local; Bacteria; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Drug Resistance, Bacterial; Haemophilus influenzae; Humans; Microbial Sensitivity Tests; Moraxella catarrhalis; Mupirocin; Pleuromutilins; Polycyclic Compounds; Skin Diseases, Bacterial; Staphylococcus; Streptococcus