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|Year : 2013 | Volume
| Issue : 2 | Page : 127-130
Retapamulin: A newer topical antibiotic
D Dhingra1, A Parakh2, S Ramachandran2
1 Department of Pediatrics, Maulana Azad Medical College and Associated Lok Nayak Hospital, New Delhi, India
2 Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi, India
|Date of Submission||10-Mar-2013|
|Date of Decision||08-Apr-2013|
|Date of Acceptance||15-Apr-2013|
|Date of Web Publication||21-Jun-2013|
Department of Pediatrics, Lady Hardinge Medical College and Kalawati Saran Children's Hospital, New Delhi
Impetigo is a common childhood skin infection. There are reports of increasing drug resistance to the currently used topical antibiotics including fusidic acid and mupirocin. Retapamulin is a newer topical agent of pleuromutilin class approved by the Food and Drug Administration for treatment of impetigo in children and has been recently made available in the Indian market. It has been demonstrated to have low potential for the development of antibacterial resistance and a high degree of potency against poly drug resistant Gram-positive bacteria found in skin infections including Staphylococcus aureus strains. The drug is safe owing to low systemic absorption and has only minimal side-effect of local irritation at the site of application.
Keywords: Impetigo, retapamulin, topical antibiotics
|How to cite this article:|
Dhingra D, Parakh A, Ramachandran S. Retapamulin: A newer topical antibiotic. J Postgrad Med 2013;59:127-30
| :: Introduction|| |
Uncomplicated skin infections are one of the most common reasons for doctor visits particularly in children.  Impetigo is the most common and highly contagious superficial skin infection caused by gram-positive organisms viz Staphylococcus aureus and Streptococcus pyogenes.  Topical antibiotics such as fusidic acid and mupirocin have remained the mainstay of treatment. Commonly used topical antibiotics are summarized in [Table 1]. However, multidrug resistance amongst S. aureus is now a widespread problem.
|Table 1: Comparison of various topical antibiotics used in skin infections|
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Retapamulin, a new antibacterial approved by Food and Drug administration (FDA) in 2007 for topical treatment of impetigo in children above 9 months has been recently made available in Indian market. This article briefly highlights the clinical pharmacology, indications, and therapeutic efficacy of this drug in Indian perspective.
| :: Pharmacology|| |
Retapamulin is a derivative of pleuromutilin, derived from Pleurotus mutilins, now called clitopilus scyphoides, an edible mushroom. 
| :: Mechanism of Action|| |
The pleuromutilin class has a unique mode of action, which involves inhibition of protein synthesis by primarily inhibiting ribosomal activity at three sites: By selectively binding to a site on the 50S subunit of the bacterial ribosome, binding to protein L3 at site P of the ribosome and inhibiting ribosomal peptidyl transferase activity. This is a novel site of binding, which differs from other ribosome binding non pleuromutilin antibiotics, which minimizes development of resistance against retapamulin. 
| :: Pharmacokinetics|| |
The drug is 94% protein bound and is primarily metabolized in the liver by mono-oxygenation and N demethylation. It has a low bioavailability and hence systemic side effects are low after local application.
| :: Dose|| |
A thin layer of retapamulin is to be applied for topical treatment of impetigo (up to 100 cm 2 in total area in adults or 2% total body surface area in children 9 months and above).  Before application affected skin may be washed and pat dried with a towel. Gently and thoroughly the ointment may be massaged over the affected area avoiding contact with eyes or mouth. The area may be covered with a thin sterile bandage. 
| :: Antimicrobial Spectrum|| |
Retapamulin is effective against gram-positive organisms and only some gram-negative organisms. It is active against S. aureus, S. pyogenes, Streptococcus agalactia, β hemolytic streptococci, streptococcus viridians, and coagulase negative staphylococci.  Retapamulin has shown significant in vitro activity against anaerobes. In a study evaluating 232 anaerobic isolates, at a level of <2 mg/L retapamulin was found to be inhibiting 90% strains. Based on inhibitory concentrations, retapamulin was found to be more effective than clindamycin, metronidazole and ceftriaxone against bacteroides fragilis, clostridium perfringes, propionibacterium acnes. 
| :: Drug Interactions|| |
Drug interactions are few owing to low systemic absorption. The drug is primarily metabolized by Cytochrome P450 (CYP) 3A4, but its administration is not seen with alteration of metabolism of other substrates of CYP3A4. The drug does not require alterations in dosages in patients with renal or hepatic impairment. 
| :: Indications|| |
The US FDA approved retapamulin 1% for use in adults and children >9 months and older for the topical treatment of impetigo (up to 100 cm 2 area in adults and 2% total body surface area in pediatric patients). However, in the European Union retapamulin 1% is approved for use in patients with impetigo or those with infected lacerations, abrasions, sutured wounds without abscesses.  However, retapamulin is not indicated for impetigo secondary to methicillin resistant Staphylococcus aureus (MRSA). 
| :: Formulation|| |
It is available as 10 mg retapamulin/1 g of ointment in 5, 10, 15, and 30 g tubes.
| :: Adverse Drug Reactions|| |
Retapamulin treatment has not been seen to be associated with any major side effects. The most common treatment related adverse effect noted is application site irritation.  There have been few reports of patients developing contact dermatitis secondary to application of retapamulin; however, in all these patients the dermatitis responded to discontinuation of retapamulin. 
| :: Studies|| |
Retapamulin has been compared in in vitro microbiological studies and clinical randomized controlled trials (RCT) with placebo, other topical antibiotics, and oral drugs such as cephalexin for treatment of impetigo in children >9 months of age. The clinical studies are summarized in [Table 2] and in vitro studies in [Table 3].
Retapamulin (5 days) has been compared with oral antibiotics such as oral cephalexin (10 days) for treatment of secondarily infected dermatitis.  (clinical efficacy/microbiologic success: Retapamulin 85.9%/87.2% versus oral cephalexin 89.7%/91.8%) and secondarily infected traumatic lesions (SITLs) (Clinical success: Retapamulin 89.5%; oral cephalexin 91.9%) and has been found to be non-inferior to cephalexin. 
Retapamulin has also been found to be non-inferior to fusidic acid in a large multicentric non-inferiority blinded RCT with similar clinical and bacteriological response rates: retapamulin (99.1%, 99.2%) and fusidic acid (94%, 93%) (P≤0.022).  There have been no comparative clinical studies with any other topical antibiotic such as mupirocin. When compared to a placebo in a double blind randomized trial retapamulin was found to be superior (success rate 85.6% vs. 52.1%, P>0.0001).  In a recent single center open labeled pilot study from USA Kircik evaluated the efficacy and tolerability of retapamulin for the treatment of infected atopic dermatitis. Application of retapamulin produced a mean 8.1-point reduction from baseline in the mean Skin Infection Rating Scale score with the majority of subjects achieved clinical cure.  Given its efficacy and good tolerability retapamulin 1% ointment needs to be further evaluated for this indication.
Retapamulin has shown significant in vitro activity against methicillin sensitive staphylococcus aureus and MRSA. Retapamulin has been compared to mupirocin, oxacillin, and erythromycin resistant strains of S. aureus and has shown consistent minimum inhibiting concentration (MIC) required to inhibit 90% of isolates MIC 90 of 0.06 μg/ml.  Significant in vitro activity of retapamulin has also been shown against S. aureus resistant to fusidic acid.  Favorable activity of retapamulin has also been recorded against MRSA (MIC 90 -0.12 μg/ml), but not against MRSA harbouring cfr gene, which expresses methyl transferase and also confers cross resistance to lincosamides.  Retapamulin has shown comparable in vitro activity against S. pyogenes as well.  When compared against S. pyogenes with other topical antibiotics, retapamulin showed the highest intrinsic activity with MIC 90 ranging from ≤0.015 μg/ml to 0.12 μg/ml. 
| :: Conclusions|| |
Retapamulin appears to be a promising drug for treatment of impetigo and other SITLs resulting due to S. aureus and S. pyogenes. The drug with its novel site of action, topical formulation, and shorter duration of action and less frequent dosing will help to ensure compliance and also prevent the development of resistance to antibacterial agents. The drug is safe and has poor systemic absorption. Retapamulin is a convenient and safe therapeutic option for the treatment of impetigo and SITLs for all age groups including children.
| :: References|| |
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[Table 1], [Table 2], [Table 3]