Evidence Based Answers Clinical Inquiries from the Family Physicians Inquiries Network

Cindy W. Su, MD, and Sean Gaskie, MD What is the best treatment for Santa Rosa Family Medicine Residency Program, oral thrush in healthy infants? Santa Rosa, Calif Barbara Jamieson, MLS Medical College of Wisconsin, Milwaukee Evidence-based answer Nystatin oral suspension is a safe first- oral gel is also more effective than nystatin line therapy; fluconazole is more effective suspension, but is not commercially (strength of recommendation [SOR]: B, 1 available in the United States (SOR: B, small randomized controlled trial [RCT]) one small RCT). Gentian violet may be but has not been approved by the Food effective, but it stains skin and clothes and and Drug Administration (FDA) for use in is associated with mucosal ulceration (SOR: immunocompetent infants. Miconazole B, 1 small retrospective cohort study). ® Dowden Health Media Clinical commentary FCopyrightluconazole isn’tFor worth personal the higher cost usemature. only This review doesn’t convince me I reassure parents that oral thrush in that fluconazole, which costs more than infants is rarely a sign of serious illness nystatin, is worth the added expense. and recommend nystatin suspension Gentian violet is very messy, and I rarely fast track 0.5 cc qid––a smaller dose than reported recommend it. For refractory thrush in Fluconazole is in this review. Larger doses are more often breastfed infants, I recommend that the spit out or swallowed, and at the smaller mother apply a topical antifungal to the more effective dose, a 60-mL bottle suppresses the nipple area. than nystatin oral yeast adequately for 2 weeks. My goal Daniel Triezenberg, MD suspension, but is to suppress yeast overgrowth until the St. Joseph Regional Medical Center, costs more and is infant’s immune system and bacterial flora South Bend, Ind an off-label use for healthy infants z Evidence summary RCT assigned 83 immunocompetent Few studies have compared treatment infants with culture-positive oral thrush options for oropharyngeal candidiasis in to receive either 25 mg miconazole oral immunocompetent infants. In a survey of gel (not commercially available in the 312 health care providers, approximately United States) or nystatin suspension (1 75% of the respondents reported treat- mL of 100,000 IU/mL) qid after meals. ing thrush with oral nystatin, citing fewer The clinical cure rate, defined as absence side effects and lower cost.1 However, ny- of plaques by day 12, was significantly statin has proved less effective than either higher in the miconazole group (99% for miconazole gel or oral fluconazole. miconazole, 54% for nystatin; P<.0001, number needed to treat [NNT]=2). The Nystatin is safe and available, eradication rate, confirmed by cultures but other options work better collected in a blinded manner on the Miconazole vs nystatin. An unblinded day of clinical cure, was also higher in

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For mass reproduction, content licensing and permissions contact Dowden Health Media. the miconazole group (55.7% for mi- Gentian violet is effective, conazole, 15.2% for nystatin; P<.0001, but messy and irritating NNT=3). In successfully treated pa- A retrospective cohort study that re- tients, infection recurred with similar viewed 69 cases of oral thrush showed frequency in both treatment groups that gentian violet achieved a 75% cure within 4 weeks (miconazole, 12.4%; rate in an average of 11 days (compared nystatin, 13.0%). Side effects—mostly to 55% in 10 days for nystatin). Both vomiting and, infrequently, diarrhea— treatments shortened the duration of were rare in both groups (miconazole, illness compared with the average of 4.5%; nystatin 3.5%).2 34 days for untreated children.6 How- An earlier, unblinded RCT of 95 ever, gentian violet can stain skin and infants compared miconazole gel to 2 clothes, and case studies have shown an nystatin oral gels (gel A: 250,000 IU/g association with ulceration of the buccal with 250,000 IU administered as single mucosa.7 dose; gel B: 100,000 IU/g with 50,000 IU administered as single dose). Each Recommendations medication was given qid over the A thorough literature search through course of 8 to 14 days. The study con- the Cochrane Database Systematic Re- firmed higher clinical cure rates with views, Agency for Healthcare Research miconazole gel (85.1% for miconazole and Quality, National Guideline Clear- vs 42.8% for nystatin gel A [P<.0007, inghouse, and Medline did not yield any NNT=2] and 48.5% for nystatin gel B guidelines or consensus statements from [P<.004, NNT=3]).3 other organizations or specialty groups Fluconazole vs nystatin. In the only on treating oropharyngeal candidiasis in prospective RCT (unblinded) to com- infants. Neither the American Academy pare oral suspensions of fluconazole of Pediatrics nor the Infectious Diseases and nystatin, 34 infants were random- Society of America has issued applicable ized to receive either nystatin (1 mL practice guidelines. n of 100,000 IU/mL) qid for 10 days fast track or fluconazole (3 mg/kg) once a day References Refractory thrush for 7 days. Mothers of breastfed in- 1. Brent NB. Thrush in the breastfeeding dyad: results of a survey on diagnosis and treatment. Clin Pedi- in breastfed fants applied nystatin cream to their atr. 2001;40:503-506. nipples twice a day for the duration 2. Hoppe JE. Treatment of oropharyngeal candidiasis infants may of the infant’s treatment. The clinical in immunocompetent infants: a randomized multi- respond cure rate—defined as absence of oral center study of miconazole gel vs. nystatin suspen- sion. The Antifungals Study Group. Pediatr Infect to a topical plaques at the end of therapy (day 10 Dis J. 1997;16:288-293. for the nystatin group, day 7 for the 3. Hoppe JE, Hahn H. Randomized comparison of antifungal applied two nystatin oral gels with miconazole oral gel for fluconazole group)—was significantly treatment of oral thrush in infants. Antimycotics to the mother’s higher in the group treated with fluco- Study Group. Infection. 1996;24:136-139. nipples nazole (100% for fluconazole, 32% for 4. Goins RA, Ascher D, Waecker N, et al. Compari- son of fluconazole and nystatin oral suspensions nystatin; P<.0001, NNT=2). The eradi- for treatment of oral candidiasis in infants. Pediatr cation rate was also higher with fluco- Infect Dis J. 2002;21:1165-1167. nazole (73.3% for fluconazole, 5.6% 5. Flynn PM, Cunningham CK, Kerkering T, et al. Oro- pharyngeal candidiasis in immunocompromised for nystatin; P<.0001, NNT=2). The children: a randomized, multicenter study of orally patients treated with fluconazole ex- administered fluconazole suspension versus- ny 4 statin. The Multicenter Fluconazole Study Group. perienced no side effects. Fluconazole J Pediatr. 1995;127:322-328. has been shown to be effective, safe, 6. Kozinn PJ, Taschdjian CL, Dragutsky D, et al. and easy to use to treat thrush in im- Therapy of oral thrush: a comparative evaluation 5 of gentian violet, mycostatin, and amphotericin B. munocompromised children, but has Monographs on Therapy. 1957;2:16-24. not been approved by the FDA for use 7. leung AK. Gentian violet in the treatment of oral in healthy infants. candidiasis. Pediatr Infect Dis J. 1988;7:304-305.

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