CKS found no evidence to guide practice on what to do if initial treatment is not effective; therefore, recommendations are pragmatic.

Treatment failure

• Most controlled trials have shown positive results from topical and oral antibiotics after 1 week [George and Rubin, 2003; Koning et al, 2003]. If the condition is not improving after this time, or is deteriorating, it is reasonable to extend treatment, while waiting for bacterial sensitivity data.
• Although topical fusidic acid is still regarded as the first-line choice by most specialists, there is increasing evidence from observational studies to suggest that bacterial resistance to it is a growing problem [Ravenscroft et al, 2000; Osterlund et al, 2002; Tveten et al, 2002; O'Neill et al, 2004]. Therefore, if treatment failure occurs with fusidic acid, an alternative such as topical retapamulin should be considered, provided infection has not become widespread.
• Switching from flucloxacillin to a different oral antibiotic (for example erythromycin or clarithromycin) is not recommended as this is unlikely to be of benefit. In this situation there is the possibility that the infection is caused by meticillin-resistant Staphylococcus aureus (MRSA) and swabs are necessary to confirm or exclude this.

Retapamulin

• Expert opinion from a narrative review recommended that retapamulin is a suitable second-line treatment for people who have not responded to topical fusidic acid [DTB, 2008].
• There is evidence from a randomized controlled trial that retapamulin is as effective as fusidic acid in the treatment of impetigo [Oranje et al, 2007].
• In contrast to fusidic acid, retapamulin has a relatively broad spectrum of activity. It acts by a different mechanism to other topical antibiotics, and development of bacterial resistance is slow (and, as it is not used systemically, it is of less concern) [Yang and Keam, 2008]. On this basis, retapamulin is a reasonable second-line choice, providing the impetigo has not spread extensively.
• It should be noted that the use of retapamulin for longer than 5 days is off licence [ABPI Medicines Compendium, 2008b], and use of topical antibiotics for longer than 2 weeks should be discouraged because of the risk of contact sensitization and development of antibiotic resistance [Yang and Keam, 2008].

Nasal staphylococcal carriage

• The recommendation for the detection and subsequent management of nasal staphylococcal carriage is based on expert opinion from CKS reviewers. Studies have shown that nasal carriage of S. aureus increases the risk of developing staphylococcal skin infections such as boils and cellulitis [Ladhani and Garbash, 2005], and it is not unreasonable to suppose there is a similar mechanism occurring with recurrent impetigo.