The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform

Ribhi Shawar - One of the best experts on this subject based on the ideXlab platform.

  • Medicine Development Center,
    2013
    Co-Authors: Ribhi Shawar, Marybeth Dalessandro, Monique Twynholm, Harmony Garges, Nicole Scangarella-oman, Medicine Development Centre, Correspondence Nicole Scangarella-oman
    Abstract:

    Topical Retapamulin in the managemen

  • microbiological profile of a new topical antibacterial Retapamulin ointment 1
    Expert Review of Anti-infective Therapy, 2009
    Co-Authors: Nicole Scangarellaoman, Ribhi Shawar, S Bouchillon, Daryl J Hoban
    Abstract:

    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.

  • topical Retapamulin in the management of infected traumatic skin lesions
    Therapeutics and Clinical Risk Management, 2008
    Co-Authors: Ribhi Shawar, John J Breton, Nicole Scangarellaoman, Marybeth Dalessandro, Monique Twynholm, Harmony Garges
    Abstract:

    Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically 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-specific cross-resistance 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.

  • Genetic Characterization of Vga ABC Proteins Conferring Reduced Susceptibility to Pleuromutilins in Staphylococcus aureus
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: Daniel R Gentry, Nicole Scangarella, Ribhi Shawar, Stephen Rittenhouse, Lynn Mccloskey, Michael N. Gwynn, David J Holmes
    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.

  • Topical Retapamulin in the management of infected traumatic skin lesions
    Dove Medical Press, 2008
    Co-Authors: Ribhi Shawar, Marybeth Dalessandro, Nicole Scangarella-oman, John Breton, Monique Twynholm
    Abstract:

    Ribhi Shawar1, Nicole Scangarella-Oman1, MaryBeth Dalessandro2, John Breton2, Monique Twynholm3, Gang Li4, Harmony Garges51Infectious Disease Center for Excellence in Drug Discovery, GlaxoSmithKline, Collegeville, PA, USA; 2Anti-infectives Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA; 3Infectious Diseases Medicine Development Centre Europe, GlaxoSmithKline, Greenford, Middlesex, UK; 4MDC BDS – Infectious Disease, GlaxoSmithKline, Collegeville, PA, USA; 5Anti-infectives Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC, USAAbstract: Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically 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-specific cross-resistance 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.Keywords: Retapamulin, traumatic skin lesions, topical antibiotic, skin infections, Staphylococcus aureu

Nicole Scangarella - One of the best experts on this subject based on the ideXlab platform.

  • Genetic Characterization of Vga ABC Proteins Conferring Reduced Susceptibility to Pleuromutilins in Staphylococcus aureus
    Antimicrobial Agents and Chemotherapy, 2008
    Co-Authors: Daniel R Gentry, Nicole Scangarella, Ribhi Shawar, Stephen Rittenhouse, Lynn Mccloskey, Michael N. Gwynn, David J Holmes
    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.

  • efficacy and safety of Retapamulin ointment as treatment of impetigo randomized double blind multicentre placebo controlled trial
    British Journal of Dermatology, 2008
    Co-Authors: Sander Koning, Nicole Scangarella, Olivier Chosidow, Monique Twynholm, J C Van Der Wouden, K P Singh, Arnold P Oranje
    Abstract:

    BACKGROUND: Impetigo is a common skin infection, primarily caused by Staphylococcus aureus and mainly occurring in children. It is usually treated topically with antibiotics to achieve a quick cure and prevent spread of the infection. Worldwide, resistance rates of S. aureus against commonly used antibiotics are rising. Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections. OBJECTIVES: Our aim was to compare the efficacy and safety of topical application of Retapamulin ointment with topical placebo ointment in the treatment of primary impetigo. METHODS: In a randomized, double-blind, multicentre study, patients received either topical Retapamulin ointment 1% twice daily for 5 days or topical placebo. Patients were enrolled into the study for 14 days and attended the clinic for three visits during which clinical and laboratory evaluations were performed. RESULTS: Two hundred and thirteen patients were randomized, with 139 evaluable patients in the Retapamulin group and 71 in the placebo group. Based on the primary efficacy endpoint of clinical response after 7 days (intention to treat), Retapamulin ointment was superior to placebo (success rate 85.6% vs. 52.1%; P<0.0001). Similar results were found in the per protocol analysis and in the subgroup of patients who had a pathogen isolated at baseline. The most common adverse effect, pruritus at the application site, was reported by 6% and 1% of patients in the Retapamulin and placebo groups, respectively. CONCLUSIONS: This study shows that topical Retapamulin is effective and safe in the treatment of primary impetigo, offering a new treatment option.

  • topical Retapamulin ointment 1 versus sodium fusidate ointment 2 for impetigo a randomized observer blinded noninferiority study
    Dermatology, 2007
    Co-Authors: Arnold P Oranje, Nicole Scangarella, Ribhi Shawar, Olivier Chosidow, Sarvajnamurthy Sacchidanand, Gail Todd, Krishan Singh, Monique Twynholm
    Abstract:

    Background: Retapamulin is a novel pleuromutilin antibacterial developed for topical use. Objective: To compare the efficacy and safety of Retapamulin ointment, 1

  • topical Retapamulin ointment 1 wt wt twice daily for 5 days versus oral cephalexin twice daily for 10 days in the treatment of secondarily infected dermatitis results of a randomized controlled trial
    Journal of The American Academy of Dermatology, 2006
    Co-Authors: Lawrence Charles Parish, Joseph L Jorizzo, John J Breton, Joseph William Hirman, Nicole Scangarella, Ribhi Shawar, Scott White
    Abstract:

    Background New antibacterial agents with activity against pathogenic strains resistant to established antibiotics are needed to treat patients with secondarily infected dermatitis (SID). Objective We sought to determine the clinical safety and efficacy of topical Retapamulin ointment 1% versus oral cephalexin for the treatment of SID. Methods 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. Results 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. Limitations 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. Conclusions 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.

  • Retapamulin ointment twice daily for 5 days vs oral cephalexin twice daily for 10 days for empiric treatment of secondarily infected traumatic lesions of the skin
    Skinmed, 2006
    Co-Authors: Almena Free, Joseph William Hirman, Nicole Scangarella, Ribhi Shawar, Eli Roth, Marybeth Dalessandro, Scott White
    Abstract:

    Introduction: Retapamulin is a novel, topical antibacterial of the pleuromutilin class in development for the treatment of secondarily infected traumatic lesions of the skin. Methods: The efficacy, safety, and tolerability of topical Retapamulin ointment, 1% for 5 days twice daily was evaluated in 2 identical, randomized, double-blind, double-dummy, multicenter studies vs oral cephalexin, 500 mg twice daily for 10 days, in 1904 patients with secondarily infected traumatic lesions. Results: Clinical success rates were 89.5% in protocol-adherent patients receiving Retapamulin compared with 91.9% for cephalexin (treatment difference, −2.5% [95% confidence interval, −5.4% to 0.5%]). In patients with Staphylococcus aureus or Streptococcus pyogenes at baseline, clinical success was 89.2% (365/409) for Retapamulin and 92.6% (63/68) for cephalexin. Safety and tolerability were similar between treatments. Noncompliance (defined as using or taking <80% of doses) was recorded in 8.0% (51/636) of patients taking cephalexin compared with 0.39% (5/1268) of patients receiving Retapamulin. Conclusions: Retapamulin offers a novel, effective, and convenient topical treatment for secondarily infected traumatic lesions.

Nicole Scangarellaoman - One of the best experts on this subject based on the ideXlab platform.

Monique Twynholm - One of the best experts on this subject based on the ideXlab platform.

  • Medicine Development Center,
    2013
    Co-Authors: Ribhi Shawar, Marybeth Dalessandro, Monique Twynholm, Harmony Garges, Nicole Scangarella-oman, Medicine Development Centre, Correspondence Nicole Scangarella-oman
    Abstract:

    Topical Retapamulin in the managemen

  • topical Retapamulin in the management of infected traumatic skin lesions
    Therapeutics and Clinical Risk Management, 2008
    Co-Authors: Ribhi Shawar, John J Breton, Nicole Scangarellaoman, Marybeth Dalessandro, Monique Twynholm, Harmony Garges
    Abstract:

    Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically 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-specific cross-resistance 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.

  • efficacy and safety of Retapamulin ointment as treatment of impetigo randomized double blind multicentre placebo controlled trial
    British Journal of Dermatology, 2008
    Co-Authors: Sander Koning, Nicole Scangarella, Olivier Chosidow, Monique Twynholm, J C Van Der Wouden, K P Singh, Arnold P Oranje
    Abstract:

    BACKGROUND: Impetigo is a common skin infection, primarily caused by Staphylococcus aureus and mainly occurring in children. It is usually treated topically with antibiotics to achieve a quick cure and prevent spread of the infection. Worldwide, resistance rates of S. aureus against commonly used antibiotics are rising. Retapamulin belongs to a newly developed class of antibiotics for the treatment of uncomplicated skin infections. OBJECTIVES: Our aim was to compare the efficacy and safety of topical application of Retapamulin ointment with topical placebo ointment in the treatment of primary impetigo. METHODS: In a randomized, double-blind, multicentre study, patients received either topical Retapamulin ointment 1% twice daily for 5 days or topical placebo. Patients were enrolled into the study for 14 days and attended the clinic for three visits during which clinical and laboratory evaluations were performed. RESULTS: Two hundred and thirteen patients were randomized, with 139 evaluable patients in the Retapamulin group and 71 in the placebo group. Based on the primary efficacy endpoint of clinical response after 7 days (intention to treat), Retapamulin ointment was superior to placebo (success rate 85.6% vs. 52.1%; P<0.0001). Similar results were found in the per protocol analysis and in the subgroup of patients who had a pathogen isolated at baseline. The most common adverse effect, pruritus at the application site, was reported by 6% and 1% of patients in the Retapamulin and placebo groups, respectively. CONCLUSIONS: This study shows that topical Retapamulin is effective and safe in the treatment of primary impetigo, offering a new treatment option.

  • Topical Retapamulin in the management of infected traumatic skin lesions
    Dove Medical Press, 2008
    Co-Authors: Ribhi Shawar, Marybeth Dalessandro, Nicole Scangarella-oman, John Breton, Monique Twynholm
    Abstract:

    Ribhi Shawar1, Nicole Scangarella-Oman1, MaryBeth Dalessandro2, John Breton2, Monique Twynholm3, Gang Li4, Harmony Garges51Infectious Disease Center for Excellence in Drug Discovery, GlaxoSmithKline, Collegeville, PA, USA; 2Anti-infectives Medicine Development Center, GlaxoSmithKline, Collegeville, PA, USA; 3Infectious Diseases Medicine Development Centre Europe, GlaxoSmithKline, Greenford, Middlesex, UK; 4MDC BDS &ndash; Infectious Disease, GlaxoSmithKline, Collegeville, PA, USA; 5Anti-infectives&nbsp;Medicine Development Center, GlaxoSmithKline, Research Triangle Park, NC, USAAbstract: Retapamulin is a novel semisynthetic pleuromutilin antibiotic specifically 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-specific cross-resistance 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.&nbsp;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.Keywords: Retapamulin, traumatic skin lesions, topical antibiotic, skin infections, Staphylococcus aureu

  • topical Retapamulin ointment 1 versus sodium fusidate ointment 2 for impetigo a randomized observer blinded noninferiority study
    Dermatology, 2007
    Co-Authors: Arnold P Oranje, Nicole Scangarella, Ribhi Shawar, Olivier Chosidow, Sarvajnamurthy Sacchidanand, Gail Todd, Krishan Singh, Monique Twynholm
    Abstract:

    Background: Retapamulin is a novel pleuromutilin antibacterial developed for topical use. Objective: To compare the efficacy and safety of Retapamulin ointment, 1

Michael R Jacobs - One of the best experts on this subject based on the ideXlab platform.

  • Retapamulin focus on its use in the treatment of uncomplicated superficial skin infections and impetigo
    Expert Review of Dermatology, 2010
    Co-Authors: Michael R Jacobs
    Abstract:

    Staphylococcus aureus and Streptococcus pyogenes are the predominant bacterial pathogens associated with uncomplicated superficial skin infections and impetigo. Treatment of these infections has been compromised by the development of antimicrobial resistance, including resistance to β-lactams (‘methicillin’ resistance), fluoroquinolones, macrolides, clindamycin and mupirocin in S. aureus, and to macrolides and clindamycin in S. pyogenes. Retapamulin is a semisynthetic antimicrobial agent belonging to the pleuromutilin class, which prevents protein synthesis in bacteria via a unique mode of action. This agent has in vitro activity against staphylococci and streptococci resistant to other classes of agents, including methicillin-resistant S. aureus, and has a low potential for the development of mutational resistance. Over 3000 patients were studied in clinical trials of Retapamulin, which is now the first pleuromutilin introduced into human use as a topical agent for the treatment of skin and skin structur...

  • Retapamulin a semisynthetic pleuromutilin compound for topical treatment of skin infections in adults and children
    Future Microbiology, 2007
    Co-Authors: Michael R Jacobs
    Abstract:

    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.

  • activity of Retapamulin against streptococcus pyogenes and staphylococcus aureus evaluated by agar dilution microdilution e test and disk diffusion methodologies
    Antimicrobial Agents and Chemotherapy, 2006
    Co-Authors: Glenn A Pankuch, Michael R Jacobs, Gengrong Lin, Dianne B Hoellman, Caryn E Good, Peter C Appelbaum
    Abstract:

    The in vitro activity of Retapamulin against 106 Staphylococcus aureus isolates and 109 Streptococcus pyogenes isolates was evaluated by the agar dilution, broth microdilution, E-test, and disk diffusion methodologies. Where possible, the tests were performed by using the CLSI methodology. The results of agar dilution, broth microdilution, and E-test (all with incubation in ambient air) for S. aureus yielded similar MICs, in the range of 0.03 to 0.25 μg/ml. These values corresponded to zone diameters between 25 and 33 mm by the use of a 2-μg Retapamulin disk. Overall, 99% of the agar dilution results and 95% of E-test results for S. aureus were within ±1 dilution of the microdilution results. For S. pyogenes , the MICs obtained by the agar and broth microdilution methods (both after incubation in ambient air) were in the range of 0.008 to 0.03 μg/ml, and E-test MICs (with incubation in ambient air) were 0.016 to 0.06 μg/ml. For S. pyogenes , 100% of the agar dilution MIC results were within ±1 dilution of the broth microdilution results. E-test MICs (after incubation in ambient air) were within ±1 and ±2 dilutions of the broth microdilution results for 76% and 99% of the isolates, respectively. E-test MICs for S. pyogenes strains in CO 2 were up to 4 dilutions higher than those in ambient air. Therefore, it is recommended that when Retapamulin MICs are determined by E-test, incubation be done in ambient air and not in CO 2 , due to the adverse effect of CO 2 on the activity of this compound. Diffusion zones (with incubation in CO 2 ) for S. pyogenes were 18 to 24 mm. Retapamulin MICs for all strains by all methods (with incubation in ambient air) were ≤0.25 μg/ml. These results demonstrate that S. pyogenes (including macrolide-resistant strains) and S. aureus (including methicillin-resistant and vancomycin-nonsusceptible strains) are inhibited by very low concentrations of Retapamulin and that all four testing methods are satisfactory for use for susceptibility testing.