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Selective Fluconazole Prophylaxis

McCrossan BA, McHenry E,  O’Neill F, et al. Selective fluconazole prophylaxis in high-risk babies to reduce invasive fungal infection.  Archives of Disease in Childhood – Fetal and Neonatal Edition 2007;92:F454-F458.  Full Text | Full Text (PDF)

Objectives: To evaluate the impact of selective fluconazole prophylaxis on incidence of invasive fungal infection and emergence of fluconazole resistance in neonatal intensive care.
Design: Retrospective study of very low birth weight (VLBW) babies (<1500 g birth weight) admitted to a neonatal intensive care unit (NICU) in the period 1 year before and after the implementation of an antifungal prophylaxis guideline.
Patients: VLBW babies with an additional risk factor: colonization of Candida species from surface sites with a central venous catheter; third generation cephalosporin treatment; or total duration of antibiotic treatment >10 days.
Fluconazole protocol: Fluconazole 6 mg/kg for 3 weeks. Dose interval is every 72 h during the first 2 weeks of life. Thereafter, dose interval is reduced to every 48 h until 3 weeks old when daily fluconazole is given. Fluconazole is administered orally when enteral feeding achieved.
Results: 121 and 107 VLBW babies were admitted to the NICU in the year before and after the guideline were implemented, respectively. Data were available in 110 and 102 charts. 33/110 and 31/102 babies were eligible for fluconazole prophylaxis in the period before and after guideline implementation. 6/33 babies eligible for prophylaxis developed culture proven Candida sepsis before compared with no (0/31) babies after the guideline was implemented (p = 0.03). One baby (1/31) did develop probable Candida sepsis in the post guideline implementation period. During both study periods all Candida isolates remained fully susceptible to fluconazole.
Conclusions: Selective antifungal prophylaxis has reduced invasive fungal sepsis in one NICU without evidence of fluconazole resistance emerging.


Comments:  There are a few other studies on fluconazole prophylaxis, but still more studies are needed to prove it. Fungal prophylaxis is not the main stream in many centers. Many centers still not using antifungal as a prophylaxis at all.  JMK.


Editor’s Comment: The primary difference between this study and previous studies of fluconazole prophylaxis is the patient selection criteria.  Previous studies (see 2-002, 6-034, 7-037, 8-035) used only weight criteria (< 1000 or < 1500 gm) for eligibility for fungal prophylaxis.  The present study requires weight < 1500 gm plus another risk factor.  The results are the same – fluconazole prophylaxis works.     The risks of this prophylaxis include cholestasis (see 7-037) and development of antimicrobial resistance.  I would not recommend the use of fluconazole prophylaxis unless the fungal sepsis rate in your NICU remains high (> 4% in VLBW babies) despite other control measures.  ABK.

Additional comments:

Date: 02 Dec 2007
Time: 20:26:08

Ample data now exist that either prophylaxis of all babies with fluconazole will prevent colonization and invasive disease. There is a nice Cochrane review on the topic which concludes that the main concern is development of resistant strains of yeast. This current study, however needs to be viewed with some level of skepticism in that it was entirely retrospective and unblinded. However, the approach is rational. In the Kaufman studies, all babies were treated, but there are ways to choose babies at higher risk and not over-expose lower risk patients, which this retrospecive analysis does. I agree that units with a high attack rate for yeast should consider prophylaxis, but I am not sure what is a high attack rate. If, like Andy says, it's >4%, then one would need to treat >25 babies to prevent one infection, and that seems to be a lot to me.

UserName: David Burchfield, MD
Institution: University of Florida
telephone: 352-392-4195
email: burchdj@peds.ufl.edu


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