When to start antifungals empirically for skin and soft tissue infections?

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Last updated: February 11, 2025View editorial policy

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From the Guidelines

Empiric antifungal therapy should be started in high-risk patients with skin and soft tissue infections who remain febrile despite broad-spectrum antibiotic therapy.

Key Considerations

  • The decision to start empiric antifungal therapy should be based on the patient's underlying disease, primary immune defect, morphology of skin lesions, use of prior antimicrobial prophylaxis, allergy history, and inherent and local profiles of antimicrobial resistance 1.
  • High-risk patients include those with prolonged neutropenia, hematological malignancies, or hematopoietic stem cell transplantation recipients 1.
  • Empiric antifungal therapy is recommended for patients who remain febrile after 4-7 days of broad-spectrum antibiotics, have clinical or radiological signs of fungal infection, or have positive serologic assay results for evidence of invasive fungal infection 1.

Antifungal Options

  • Lipid formulation of AmB, echinocandin (caspofungin or micafungin), or voriconazole are recommended antifungal options for empiric therapy 1.
  • The choice of antifungal agent should be individualized based on the patient's prior use of antifungal agents, underlying disease, and local epidemiology of fungal infections 1.

Diagnostic Workup

  • Aggressive diagnostic workups are still required even after starting empiric therapy, and the diagnosis of invasive fungal infection should be regularly reviewed 1.
  • Skin biopsy material should be obtained and evaluated in conjunction with a pathologist who is familiar with immunocompromised patients 1.

From the Research

Empirical Antifungal Treatment for Skin and Soft Tissue Infections

  • The decision to start antifungals empirically for skin and soft tissue infections should be based on the patient's risk factors and clinical presentation 2.
  • Patients taking immunosuppressive medications are at higher risk of developing fungal infections, and consideration should be given to adding antifungals to empiric treatment regimens in these cases 2.
  • Fungal necrotizing soft tissue infections are associated with high morbidity and mortality, and initiation of antifungals is associated with a significantly lower rate of in-hospital mortality 2.
  • The approach to a patient suspected of having a fungal skin and soft tissue infection is complex and usually poses a major diagnostic challenge, requiring a multidisciplinary approach and consideration of targeted antifungal therapy and/or aggressive surgical debridement 3, 4.
  • Empirical antifungal therapy refers to the initiation of an antifungal agent at the first possible clinical evidence of fungal infection, and is frequently recommended in high-risk patients to guarantee an early approach 5.

Patient Risk Factors

  • Immunocompromised patients, such as those with organ transplants, leukemia, or taking immunosuppressive medications, are at higher risk of developing fungal infections 2, 6.
  • Patients with certain underlying conditions, such as chronic obstructive pulmonary disease or rheumatoid arthritis, may also be at increased risk of fungal infections 6.

Clinical Presentation

  • Fungal skin and soft tissue infections can present with a variety of symptoms, including necrotic ulcerations or nodules, and may be associated with systemic infection 3, 6.
  • Prompt examination, biopsy, and culture are necessary to diagnose fungal infections in high-risk patients 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Antifungal Therapy in Fungal Necrotizing Soft Tissue Infections.

The Journal of surgical research, 2020

Research

Recent concepts in fungal involvement in skin and soft tissue infections.

Current opinion in infectious diseases, 2022

Research

Fungal infections of the skin and soft tissue.

Current opinion in infectious diseases, 2020

Research

Empirical antifungal treatment: a valid alternative for invasive fungal infection.

Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia, 2011

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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