retapamulin and Skin-Diseases--Infectious

In atopic dermatitis (AD), the stratum corneum of patients appears to have alterations that predispose them to colonization and invasion by various bacteria, most notably Staphylococcus aureus (S. aureus). This bacterial co-existence is accepted to be an important factor in AD disease activity. Exactly when to initiate antimicrobial treatment is controversial, but such intervention, when warranted, has repeatedly been demonstrated to improve the course of AD. However, the increase in antibiotic resistance presents a therapeutic challenge in the management of AD patients, which highlights the need for novel mechanism topical antibacterial agents. Retapamulin is a relatively new pleuromutilin antibiotic designed for topical use. In vitro studies have demonstrated its low potential for the development of antibacterial resistance and high degree of potency against Gram-positive bacteria found in skin infections, including many S. aureus strains that are resistant to methicillin, fusidic acid, and mupirocin. Clinical studies exploring the treatment of secondarily infected dermatitis reveal that the efficacy of topical retapamulin is comparable to a 10-day course of oral cephalexin or to topical fusidic acid. Retapamulin appears to be a much needed antimicrobial option for treating the AD population due to their common carriage of bacterial pathogens and frequency of infectious complications.

Topics: Administration, Topical; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Dermatitis, Atopic; Diterpenes; Drug Resistance, Bacterial; Gram-Positive Bacterial Infections; Humans; Skin Diseases, Infectious; Staphylococcal Skin Infections

Retapamulin is the first agent in the new pleuromutilin class of antibacterials to become commercially available for clinical use in humans. Retapamulin acts as a potent inhibitor of bacterial protein synthesis and has a unique mode of antibiotic action. To date, retapamulin has not demonstrated any clinically relevant, target-specific crossresistance with other antibiotic classes, and has shown a low potential for resistance selection in vitro. In preclinical studies, retapamulin demonstrated pronounced in vitro activity against staphylococcal, streptococcal and anaerobic Gram-positive clinical isolates associated with skin and skin structure infections. Clinical pharmacology studies showed low systemic exposure with topical use of retapamulin, and a favorable tolerability profile. In clinical efficacy trials involving pediatric and adult patients who received retapamulin twice daily for five days, retapamulin was highly effective in the treatment of impetigo, secondarily infected traumatic lesions and secondarily infected dermatitis. Further, the clinical efficacy and safety profile of retapamulin was comparable to that of commonly used oral and topical antibiotics. Retapamulin was also clinically effective against isolates resistant to existing therapies. As a 1% ointment, retapamulin has been approved in the United States for the treatment of impetigo and in Europe for the shortterm treatment of impetigo and infected small lacerations, abrasions and sutured wounds.

Topics: Administration, Topical; Animals; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Humans; Skin Diseases, Infectious

Retapamulin is a semisynthetic pleuromutilin compound with in vitroactivity against Gram-positive bacteria, no cross-resistance to other classes of antimicrobial agents in current use and a low potential for development of resistance. A 1% ointment formulation has been developed for clinical use, and a placebo-controlled trial of impetigo in 210 patients produced significantly higher rates of clinical and microbiological success compared with placebo - 85.6 versus 52.1% and 91.2 versus 50.9%, respectively. Additional comparative studies in over 1900 patients showed noninferiority to topical fusidic acid and oral cephalexin and a low frequency of adverse events. In 2007, retapamulin was approved in the USA for topical treatment of impetigo caused by Streptococcus pyogenes and methicillin-susceptible Staphylococcus aureus, and in the EU for topical treatment of impetigo and infected wounds caused by S. pyogenes and S. aureus, with approvals including adults and children over 9 months of age.

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Child; Child, Preschool; Diterpenes; Humans; Impetigo; Infant; Pleuromutilins; Polycyclic Compounds; Skin Diseases, Infectious; Staphylococcal Skin Infections; Treatment Outcome

New antibacterial agents with activity against pathogenic strains resistant to established antibiotics are needed to treat patients with secondarily infected dermatitis (SID).. We sought to determine the clinical safety and efficacy of topical retapamulin ointment 1% versus oral cephalexin for the treatment of SID.. Patients with SID were randomly assigned to retapamulin ointment 1% (twice daily [bid]) for 5 days, or oral cephalexin (500 mg bid) for 10 days. The primary efficacy end point was clinical response at follow-up. Secondary outcomes included microbiologic response at follow-up, safety, and compliance.. Retapamulin was as effective as cephalexin (clinical success rates at follow-up: 85.9% and 89.7%, respectively). Microbiologic success rates at follow-up were 87.2% for retapamulin and 91.8% for cephalexin. Retapamulin was well tolerated and the topical formulation was preferred over the oral drug.. An imbalance existed in the number of patients with the clinical outcome "unable to determine" (15 retapamulin, 2 cephalexin), mainly because of their failure to attend the study visit. If those who failed to attend visits (who did not withdraw as a result of drug-related events) are removed from the analysis, the clinical success rates are 89.9% for retapamulin and 89.7% for cephalexin.. Retapamulin ointment 1% (bid) for 5 days was as effective as oral cephalexin (bid) for 10 days in treatment of patients with SID, and was well tolerated.

Topics: Administration, Cutaneous; Administration, Oral; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bridged Bicyclo Compounds, Heterocyclic; Cephalexin; Child; Child, Preschool; Dermatitis; Dermatitis, Atopic; Diterpenes; Double-Blind Method; Female; Follow-Up Studies; Humans; Infant; Infant, Newborn; Male; Methicillin Resistance; Middle Aged; Ointments; Skin Diseases, Infectious; 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 methicillin-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 cephalexin, although the efficacy of retapamulin was reduced in patients with MRSA infections or superficial abscesses. Retapamulin was well tolerated in both pediatric 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: Anti-Infective Agents; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Humans; Impetigo; Mutation; Ribosomal Protein L3; Ribosomal Proteins; Skin; Skin Diseases, Infectious

Retapamulin is the first agent of the pleuromutilin class formulated as a topical antibacterial for treating skin infections. The aim of this study was to determine the antimicrobial activity of retapamulin by determining the minimal inhibitory concentration (MIC) values of this new drug and comparators against a wide range of anaerobic bacteria of human origin.. The in vitro activity of retapamulin and six comparators (amoxicillin, amoxicillin/clavulanic acid, ceftriaxone, imipenem, clindamycin and metronidazole) was evaluated against 232 anaerobic clinical isolates. MICs were determined by the CLSI reference agar dilution method (M11-A6).. Ceftriaxone, clindamycin and amoxicillin/clavulanic acid resistance rates were 54%, 42% and 9.6%, respectively, within the Bacteroides fragilis group. Despite high resistance rates to various antibiotics, retapamulin inhibited 37/52 (71%) strains of the B. fragilis group and 85/87 (98%) of the other Gram-negative bacilli at a concentration of 2 mg/L or less. All the investigated strains of Clostridium perfringens were inhibited by 1 mg/L retapamulin. Three strains of C. difficile and one strain of C. clostridioforme demonstrated decreased susceptibility to retapamulin. Based on inhibitory concentrations, retapamulin was more active than clindamycin, metronidazole and ceftriaxone against Propionibacterium acnes and anaerobic Gram-positive cocci, as all isolates were inhibited by

Topics: Anti-Bacterial Agents; Anti-Infective Agents, Local; Bacteria, Anaerobic; Bacteroides fragilis; Bridged Bicyclo Compounds, Heterocyclic; Diterpenes; Gram-Negative Anaerobic Bacteria; Gram-Positive Bacteria; Microbial Sensitivity Tests; Skin Diseases, Infectious