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Section 8 — Infectious Disease & Sepsis Verify against local policy v1.0 · July 2026 Baylor Ed. 33 cross-checked Sept 2026

Chapter 8.5 — Invasive Fungal Infection

Invasive candidiasis in the ELBW infant: risk-based suspicion, end-organ screening, line removal, and antifungal therapy — plus the role of fluconazole prophylaxis — built on West Midlands Neonatal Guidelines 2025–28 and IDSA/AAP guidance

Educational guideline — verify locally. Antifungal choice, dosing, and prophylaxis policy are unit-specific; verify against the Neonatal Formulary, local incidence, and antimicrobial/ID advice. Does not replace attending judgment.
BEDSIDE ACTION BOX

1. Overview

Overview

Invasive fungal infection in the neonate is predominantly invasive candidiasis, a serious cause of late-onset sepsis in extremely preterm infants with high mortality and neurodevelopmental morbidity. Because it disseminates and seeds end organs (eyes, brain, kidneys, heart), management requires a high index of suspicion in at-risk infants, systematic end-organ screening, source control (line removal), and adequate antifungal therapy — with prevention (fluconazole prophylaxis) in high-incidence units.

Why This Topic Matters

Candidemia in the ELBW infant is frequently underestimated and under-screened. Delayed antifungal therapy and retained lines worsen outcomes, and missed end-organ disease (endophthalmitis, CNS, renal, cardiac) leads to permanent harm.

2. Who This Guideline Applies To

Scope
  • ELBW/very preterm infants at risk of, or with, invasive candidiasis, and other rare invasive fungal infections.
  • Units considering antifungal prophylaxis policies.
  • Cross-references: late-onset sepsis (8.2), meningitis (8.4), parenteral nutrition/line care (7.2), and NEC (11.1).

3. Key Definitions

TermDefinition
Invasive candidiasisSystemic Candida infection (candidemia ± end-organ disease).
End-organ screeningEyes, brain, kidneys, and heart assessment for disseminated disease.
Fungal ballsRenal/urinary-tract fungal aggregates seen on ultrasound.
Fluconazole prophylaxisPreventive antifungal for high-risk ELBW infants in high-incidence units.

4. Risk Factors

Who Is at Risk
  • Extreme prematurity/ELBW; central venous catheters; prolonged broad-spectrum antibiotics.
  • Parenteral nutrition (especially lipids); recent abdominal surgery or NEC; H2-blockers/steroids; mucocutaneous Candida colonization.
  • Prolonged intensive care with multiple invasive devices.

5. Presentation

Non-Specific, Often "Antibiotic-Unresponsive Sepsis"
  • Signs of sepsis that do not respond to antibiotics; thrombocytopenia; hyperglycemia; new instability.
  • End-organ disease may be occult: chorioretinitis/endophthalmitis, CNS involvement, renal fungal balls, endocarditis.
  • Consider Candida in any deteriorating at-risk infant with negative bacterial cultures.

6. Work-up & End-Organ Screening

Confirm & Map Dissemination
  • Cultures: blood (fungal), urine (SPA/catheter), and CSF (LP) — Candida meningitis is common in neonates.
  • Eyes: dilated ophthalmology exam for chorioretinitis/endophthalmitis.
  • Brain: cranial imaging (ultrasound ± MRI) for CNS involvement/abscess.
  • Kidneys/urinary tract: ultrasound for fungal balls.
  • Heart: echocardiography for endocarditis/vegetations (especially with a line/persistent candidemia).

7. Management Algorithm

1
Suspect in at-risk infant
Antibiotic-unresponsive sepsis in an ELBW infant with lines/PN/prolonged antibiotics → consider Candida.
2
Culture & consider empiric antifungal
Fungal blood culture, urine, LP; start empiric antifungal in high-risk deteriorating infants per policy while awaiting results.
3
Remove/replace the line
Prompt central-line removal/replacement — retained lines perpetuate candidemia.
4
Screen end organs
Ophthalmology, cranial imaging, renal ultrasound, echocardiography; involve ID/micro.
5
Treat adequately
Antifungal per susceptibility/policy for an adequate duration after documented blood-culture clearance; longer for end-organ disease.
6
⚠ Do-not-miss
Candida meningitis (LP); endophthalmitis; renal fungal balls; endocarditis; and retained infected lines.

8. Antifungal Treatment (Verify Locally)

AgentRoleNotes
Amphotericin BCommon first-line for neonatal invasive candidiasis.Deoxycholate or lipid formulations per policy; monitor renal/electrolytes.
FluconazoleSusceptible isolates; step-down; prophylaxis.Good CSF/urine penetration; check susceptibility (not all species susceptible).
EchinocandinsSelected/refractory cases (specialist).Limited CNS/urinary penetration — caution in meningitis/renal disease.
The doses Baylor Ed. 33 states
  • Amphotericin B deoxycholate 1 mg/kg IV daily for disseminated candidiasis. Monitor BUN, creatinine and potassium frequently at the start.
  • Flucytosine 150 mg/kg/day orally in 4 divided doses may be added to amphotericin when C. albicans has infected the CNS.
  • Fluconazole 12 mg/kg daily as step-down once the infant has responded, for susceptible isolates. Duration varies with the site of infection and the clinical response.
  • Remove indwelling vascular catheters as soon as feasible, and get ID advice for any disseminated candidiasis or other invasive fungal infection.
  • Diagnostic threshold: a presumptive diagnosis rests on isolating Candida from blood, CSF, infected tissue, or urine obtained by suprapubic aspiration or catheter at ≥10⁴ CFU/mL. Invasive fungal dermatitis is diagnosed clinically and confirmed on skin biopsy histopathology.
  • Time the imaging: ophthalmology, lumbar puncture, abdominal ultrasound and echocardiography are indicated in every case of disseminated candidiasis, with contrast brain MRI for CNS disease — but perform the imaging in the late second or third week of therapy, since an early study can mislead.
  • What raises the risk: systemic corticosteroids and prolonged broad-spectrum antibiotics — third-generation cephalosporins and meropenem especially — plus parenteral nutrition, lipid emulsions, abdominal surgery and H₂ blockers. Disseminated disease concentrates in infants below 1000 g or 27 weeks.

9. Antifungal Prophylaxis

Fluconazole Prophylaxis in High-Incidence Units
  • Fluconazole prophylaxis reduces invasive candidiasis in ELBW infants and is recommended in NICUs with a high baseline incidence.
  • Eligibility (e.g., birth weight/gestation thresholds), dose, and duration are unit-specific — follow local policy based on your unit's incidence.
  • Baylor Ed. 33 puts numbers on "high incidence": the 2021 Red Book recommends routine fluconazole prophylaxis for infants under 1000 g at birth in NICUs where invasive candidiasis exceeds 10% (moderate quality evidence). Three multicentre randomized trials compared six weeks of IV fluconazole with placebo in VLBW and ELBW infants: both colonization and invasive candidiasis fell significantly, the regimen was safe, and no resistant Candida emerged in units using it for 6 and 10 years respectively.
  • Also reduce risk with antimicrobial stewardship, line-care bundles, and early enteral feeding (see 8.2/7.2).

10. Monitoring

ParameterWhenAction
Repeat blood culturesTo document clearancePersistent candidemia → line removal, imaging, ID advice.
End-organ screenAt diagnosis (± repeat)Extend therapy for end-organ disease.
Renal function/electrolytesOn amphotericinMonitor toxicity.
Line necessityDailyRemove/replace infected lines.

11. Precautions

Safety Cautions
  • Do not overlook Candida in antibiotic-unresponsive sepsis in at-risk infants.
  • Always screen end organs (eyes, brain, kidneys, heart) and do an LP (Candida meningitis is common).
  • Remove/replace infected central lines promptly.
  • Check species susceptibility (not all Candida are fluconazole-susceptible); echinocandins have poor CNS/urinary penetration.
  • Treat for an adequate duration after documented clearance; verify doses and monitor toxicity.

12. Escalation & Family Support

Family-Centered Communication
  • "Your baby has a fungal (yeast) infection in the blood, which is more common in very premature babies. We treat it with antifungal medicine and check the eyes, brain, kidneys, and heart because it can spread."
  • "We remove the drip line it may be growing on and continue treatment until the blood is clear."

13. Key Pearls

High-Value Clinical Pearls
  • Suspect invasive candidiasis in antibiotic-unresponsive sepsis in ELBW infants with lines/PN/prolonged antibiotics.
  • Screen end organs: eyes, brain, kidneys, heart; do an LP (Candida meningitis is common).
  • Remove/replace infected central lines promptly.
  • Amphotericin B is common first-line; fluconazole for susceptible species/step-down; echinocandins penetrate CNS/urine poorly.
  • Treat for an adequate duration after documented blood-culture clearance.
  • Fluconazole prophylaxis reduces candidiasis in ELBW infants in high-incidence units.

14. Common Mistakes to Avoid

MistakeWhy it harmsBetter practice
Forgetting Candida.Delayed treatment; mortality.Consider in at-risk unresponsive sepsis.
No end-organ screen/LP.Missed CNS/eye/renal/cardiac disease.Screen eyes/brain/kidneys/heart; LP.
Retaining the line.Persistent candidemia.Remove/replace promptly.
Echinocandin for meningitis.Poor CNS penetration.Amphotericin/fluconazole for CNS.
Stopping too early.Relapse.Treat adequately after clearance.

15. Board-Style High-Yield Summary

Key Takeaways
  • Invasive candidiasis: serious late-onset sepsis in ELBW infants; risk = lines, PN, prolonged antibiotics, NEC/surgery.
  • Suspect in antibiotic-unresponsive sepsis with thrombocytopenia/hyperglycemia.
  • Work-up: fungal blood culture, urine, LP; screen eyes/brain/kidneys/heart for dissemination.
  • Remove/replace infected lines; treat with amphotericin B (or fluconazole for susceptible/step-down; echinocandins selectively).
  • Treat for an adequate duration after clearance; longer for end-organ disease.
  • Fluconazole prophylaxis reduces candidiasis in ELBW infants in high-incidence units.

16. References

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