What is the next step in treating impetigo that is not responding to mupirocin (Bactroban)?

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Last updated: June 13, 2025View editorial policy

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From the Guidelines

For impetigo not responding to mupirocin (Bactroban), the next step is typically oral antibiotic therapy with a 7-day regimen of an agent active against S. aureus, such as dicloxacillin or cephalexin. According to the 2014 practice guidelines for the diagnosis and management of skin and soft tissue infections by the Infectious Diseases Society of America 1, oral therapy is recommended for patients with numerous lesions or in outbreaks affecting several people to help decrease transmission of infection. The choice of oral antibiotic should be based on the suspected causative organism, with dicloxacillin or cephalexin being suitable options for methicillin-susceptible S. aureus 1. Some key points to consider in the management of impetigo not responding to mupirocin include:

  • Obtaining a Gram stain and culture of the pus or exudates from skin lesions to help identify the causative organism 1
  • Considering the use of oral antibiotics active against MRSA, such as doxycycline, clindamycin, or sulfamethoxazole-trimethoprim, if MRSA is suspected or confirmed 1
  • Ensuring good wound care by gently washing the affected areas with soap and water, removing crusts, and keeping the areas clean and dry
  • Monitoring for signs of systemic illness or extensive involvement, which may require hospitalization for intravenous antibiotics 1.

From the FDA Drug Label

If impetigo has not improved in 3 to 5 days, contact your healthcare practitioner The next step in treating impetigo that is not responding to mupirocin (Bactroban) is to contact your healthcare practitioner for further evaluation and guidance on alternative therapy, as stated in the drug label 2.

From the Research

Impetigo Treatment Not Clearing with Mupirocin

  • Impetigo is a common bacterial skin infection that can be caused by Staphylococcus aureus or Streptococcus pyogenes 3.
  • Mupirocin is a topical antibiotic commonly used to treat impetigo, but resistance to mupirocin has been reported 3, 4.
  • If impetigo is not responding to mupirocin, alternative treatments can be considered, such as:
    • Retapamulin: a topical antibiotic effective against methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pyogenes 5, 6.
    • Fusidic acid: a topical antibiotic available in some countries, but with rising resistance rates 3, 6.
    • Ozenoxacin: a topical quinolone effective against S. aureus, including methicillin-resistant S. aureus (MRSA), and S. pyogenes 4, 6.
  • Oral antibiotic therapy can also be considered for impetigo that is not responding to topical treatment, with options including amoxicillin/clavulanate, dicloxacillin, cephalexin, clindamycin, and trimethoprim/sulfamethoxazole 3.

Considerations for Treatment

  • The increasing prevalence of antibiotic-resistant bacteria, including MRSA and mupirocin-resistant streptococcus, should be taken into account when selecting treatment 3, 4.
  • Local trends in antibiotic resistance should be considered when prescribing antibiotics 4.
  • The cost and insurance coverage of different treatments may also be a factor in choosing the best therapeutic agent 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Impetigo: diagnosis and treatment.

American family physician, 2014

Research

Interventions for impetigo.

The Cochrane database of systematic reviews, 2012

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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