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BACKGROUND

  1. Top of page
  2. BACKGROUND
  3. LITERATURE REVIEW
  4. BEST PRACTICE
  5. LEVEL OF EVIDENCE
  6. BIBLIOGRAPHY

The etiology of chronic rhinosinusitis (CRS) still remains controversial. Evidence has emerged that a fungal-mediated mechanism may be playing a role in the development of this disease process. In light of this, groups have proposed topical treatment of patients with the antifungal drug amphotericin B. Early studies showed some promise with this treatment, but more recent work has not been as positive. Is there sufficient evidence to continue to recommend this treatment for patients diagnosed with CRS?

LITERATURE REVIEW

  1. Top of page
  2. BACKGROUND
  3. LITERATURE REVIEW
  4. BEST PRACTICE
  5. LEVEL OF EVIDENCE
  6. BIBLIOGRAPHY

Chronic rhinosinusitis persists as a widespread medical problem of incompletely understood etiology. Evidence emerged beginning in the late 1990s that fungal elements are present in a large percentage of patients with CRS. This gave rise to the theory that these fungal elements or the inflammation they elicit play a role in the etiology of the disease. If this theory is true, then decreasing fungal organisms from the sinonasal tract should improve symptoms. Topical amphotericin B, a potent polyene antifungal drug with poor mucous membrane absorption, has been studied to this end beginning with the work of Ponikau et al. In this initial noncontrolled study, 51 patients were included. Patients irrigated each naris with 20 mL of amphotericin B-containing solution twice daily for at least 3 months. Outcomes included the patients' subjective opinion of their symptoms post-treatment, computed tomography (CT) findings pre- and post-treatment, and change in investigator endoscopic findings within each patient's nose following treatment. The study reported significant improvement in symptom scores, endoscopic findings, and in the amount of inflammation seen on CT scan post-treatment.1 A double-blinded randomized study was then published in 2005 by this same group comprised of 30 patients treated with the same volume but with a higher concentration of amphotericin for 6 months versus placebo. They reported significantly improved signs of inflammation on CT scan in the treatment group as well as endoscopy score. There was, however, no statistical difference in the patient symptom scores between the two groups, and the study was limited by small group sizes.2

Other studies have not been as positive about the efficacy of this treatment. In 2006 a randomized controlled trial by Ebbens et al. followed 116 patients with CRS using twice-daily rinses of 25 mL in each naris. The same concentration of amphotericin was used as that in the original paper by Ponikau et al. All patients had undergone previous sinus surgery to improve the chances of the topical agent predictably reaching the sinonasal mucosa. The study followed patients for 3 months and had patient symptom scores and endoscopic findings as the primary outcome measurements. Secondary endpoints analyzed included peak nasal inspiratory flow, polyp score, and quality-of-life (QOL) survey scores. The study found no statistical difference in the degree of improvement between the placebo and amphotericin B groups for criteria analyzed.3 Another randomized controlled trial performed by Weschta et al. utilized a high concentration of amphotericin B in a spray format 4 times a day for 8 weeks in the treatment group. They believed this was a better test of the efficacy of amphotericin itself, because high-volume rinses alone are a treatment possibly confounding the effects of drug. They again had symptom, QOL, and endoscopy scores as outcomes. A CT score as defined by Lund and Mackay after treatment was the primary outcome. Surprisingly, they found that the QOL scores were worse in the treatment group compared to the control group. On all other included criteria they found no significant differences between the two groups after treatment.4

Ebbens et al., after publishing a paper indicating topical amphotericin had no effect on clinical indicators of chronic rhinosinusitis severity, published a follow-up paper looking at the effect the drug had on molecular markers of inflammation. In their study they analyzed nasal lavages collected pre- and post-treatment from patients participating in their previously published trial. They analyzed levels of 15 separate chemokines, cytokines, and growth factors linked to the inflammatory response, including interleukin 5 and eotaxin, both thought to be important in the regulation of eosinophilic inflammation. When pre- and post-treatment levels were analyzed in both treatment and control groups, no significant difference was found for any of the analyzed markers. They concluded that amphotericin is very unlikely to have any anti-inflammatory effect either directly or indirectly.5

BEST PRACTICE

  1. Top of page
  2. BACKGROUND
  3. LITERATURE REVIEW
  4. BEST PRACTICE
  5. LEVEL OF EVIDENCE
  6. BIBLIOGRAPHY

The majority of large, recent, randomized, controlled trials have shown that topical amphotericin at a variety of concentrations, delivered via several different delivery routes, has proved ineffective in the treatment of chronic rhinosinusitis. At the evaluated concentrations, there is insufficient evidence to continue to recommend this treatment. Higher concentrations may yet prove to be effective, but further study is required.

LEVEL OF EVIDENCE

  1. Top of page
  2. BACKGROUND
  3. LITERATURE REVIEW
  4. BEST PRACTICE
  5. LEVEL OF EVIDENCE
  6. BIBLIOGRAPHY

In this paper, one level 4 paper (case series without an internal control) and four level 1 papers (randomized controlled trials) were reviewed.

BIBLIOGRAPHY

  1. Top of page
  2. BACKGROUND
  3. LITERATURE REVIEW
  4. BEST PRACTICE
  5. LEVEL OF EVIDENCE
  6. BIBLIOGRAPHY