Use of Prophylactic Fluconazole - Paediatrics - Lecture Slides, Slides of Pediatrics

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The use of prophylactic fluconazole

in very low birth weight infants

Incidence and burden of fungal infections

in the NICU

• Candida spp third most common cause of late onset

sepsis (>72 h) in VLBW (<1500g)

• 75% of infected VLBW infants will die or survive with

handicap

• Overall mortality rates estimated at 10-15%
• Case mortality rates as high as 44%
• In Canada (2003-2005): incidence 6.7% infants <

weeks*

Risk factors for candidiasis

• ELBW

• Low gestational age

• Therapies

– Intubation

– Ventilation

– Central line placement

– TPN

– Medications

• Steroids
• H2 blockers
• antibiotics

Strategies

• Optimal infection control practices

• Avoid broad spectrum antibiotic coverage

• Prompt removal of infected devices

• Prevention of colonization

30% of NICUs use some form of antifungal prophylaxis*

• Fluconazole
• Topical nystatin
• Amphoteracin B

*AAP/Neo-Peri Section questionnaire

RCTs of oral antifungal agents

Study Enrolment

Criteria

N Dosing

Schedule

Protocol Treatment

Group

Control

Group

P-value

Sims et al

<1250 67 Nystatin po

every 8 hours

Single-centre

placebo

Violaris et

al (1998)

<1500 g 21 Fluconazole vs.

nystatin

Single-centre 0/8 (0%) 4/

Wainer et

al (1992)

<1750 g 600 Miconazole po

every 8 hours

Single-centre

placebo

NS

Ozturk et

al

All infants 3991 Nystatin po

every 8 hours,

variable

Single-centre 36/

*adapted from Healy,M: NeoReviews, 2008

RCTs of fluconazole prophylaxis in neonates

Study Enrolment Criteria

N Protocol Dosing Schedule Treatment Group (IC)

Control Group (IC)

P-value

Kaufman et al (2001)

<1000 g ETT or CVC ≤ 5 days of life

100 Single-centre placebo

3mg/kg x 6 wks or less if no IV needed q72h (0-14d) q48h (15-28d) q24h (29-42d)

(4 Candida- related deaths)

Kicklighter et al (2001)

<1500 g ≤ 3 days of life

103 Single-centre placebo

6 mg/kg IV/PO For 28 days

(1 Candida- related death)

0/50 (0%) NS

Cabrera et al (2002)

<1500 g 11 Single-centre, placebo

6 mg/kg IV then PO 0/6 1/5 NS

Parikh et al (2007)

<1500 g 120 Single-centre, placebo

6 mg/kg IV then po for 28 days

15/60 (25%) NS

Manzoni et al (2007)

<1500 g ≤ 3 days of life

322 Multi-centre, placebo

6 mg/kg or 3 mg/kg qod x 30d (100- 1500g) or 45d (<1000g) or less if no IV needed

(0 Candida- related deaths)

(4 Candida- related deaths)

Optimal dosing and schedule

• Trials:

– 3-6 mg/kg

– 24-72 h intervals

– 7 different schedules

• Kaufman:

– 3mg/kg PO starting on Day 1 or 2

– Twice per week

– For up to 6 weeks

Who should receive fluconazole

prophylaxis?

• BW ≤ 750 gm
• GA ≤27 weeks
• IF BASELINE FUNGAL INFECTION RATES ARE

HIGH (eg: >5%)

• Why not ≤ 1500 gm BWs?