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FUNGAL INFECTION
IN NEONATES
DR.RAVI KUMAR
2ND
YEARPG
DEPT OF PEDIATRICS
MGMCRI
Discussion
• Introduction
• Etiology
• Epidemiology
• RiskFactors
• Clinical Manifestations
• Diagnosis
• Treatment
• Prevention
Introduction
• Among the fungal infections Candida has emerged as
an important cause of neonatal infections with
significant morbidity and mortality, especially in
LBW& ELBWinfants.
• Clinical presentations vary fromlocalized skin
infections to life-threatening systemic infection
Etiology
• Candida Infection
• Non – Candida Infections - Uncommon
Candida
• C. Albicans (60%)- most common among Candida
spp
• C. Parapsilosis.
OtherCandida Spp:
• C. Tropicalis
• C. Lusitaniae
• C. Glabrata
• C. Krusei
Non-candida Spp
• Aspergillosis
• Zygomycosis
• Malassezia Sepsis
• Trichosporonosis
• Cryptococcosis
• Coccidioidomycosis
• Blastomycosis
• Dermatophytosis.
Epidemiology
• Candida species are important hospital-acquired
pathogens in infants admitted to the NICU.
• In VLBWinfants Candida albicans is the third most
common cause of LONS.
Transmission
• Vertical transmission from the motheror
• Horizontal transmission from health care workers/
the hospital environment.
RiskFactors
• Immaturity of host defenses and
colonization with Candida before
complete establishment of normal
intestinal flora probably contribute to
the pathogenicity of Candida in the
neonate.
Clinical Manifestations
Various presentations of Candida infections:
1.Mucocutaneous candidiasis
2.Systemic candidiasis
3.Catheter-related infections
4.Focal infection
MUCOCUTANEOUS
CANDIDIASIS
1) Oral Candidiasis (Thrush)
• Irregularwhite plaques
• +/- erythematous base on the buccal/lingual mucosa
• In breastfed infants - ductal candidiasis in the
mother's breast.
• Concurrent treatment of both is necessary
• Such mother’s are advised to withhold expressed
milkuntil treatment has been instituted.
white plaques on
the innerlip,
tongue & Buccal
mucosa
TREATMENT
• Nystatin - oral suspension 1 ml (1 Lakh U/ml) is
applied to each side of the mouth Q6Hfor10 to 14
days.
• Fluconazole - 6 mg/kg IV/PO once followed by 3
mg/kg IV/PO each day can be used forsevere oral
candidiasis if nystatin oral therapy is not effective.
• Systemic fluconazole is highly effective in treating
chronic mucocutaneous candidiasis in the
immunocompromised host.
MUCOCUTANEOUS
CANDIDIASIS
2) Candida DiaperDermatitis
Discrete erythematous papules and plaques over
inguinal region with superficial scales, and satellite
lesions
TREATMENT
Effectively treated with Topical agents :
•2% nystatin ointment
•2% miconazole ointment,
•1% clotrimazole cream.
•Concomitant treatment with oral nystatin to eliminate
intestinal colonization is often recommended
•It is reasonable to use simultaneous oral and topical
therapy forrefractory candidal diaperdermatitis.
MUCOCUTANEOUS
CANDIDIASIS
3) Congenital Candidiasis
• Generalized eruptions appearon first day of life
• 2 to 4 mm erythematous macules /papules that rest
upon a 5 to 10 mm erythematous base.
• These lesions evolve into pustules, vesicles, oreven
bullae.
• Riskfactors : Prolonged ROM/Vaginal Candidiasis
SEBORRHEIC DERMATITIS
• Greasy, yellow plaques on the scalp with some
degree of hairloss.
• Cause : Presence of Malassezia spp in the oil
secretion on the skin
• Such lesions are highly prevalent during the first 4
weeks of life
Treatment :
• Gentle scrubbing of scalp
• Vaseline application
• Removal of scales using a soft brush
• Forextensive cases, topical mild corticosteroid or
antifungal is indicated.
Cradle Cap
Systemic Candidiasis
• Serious formof nosocomial infection in VLBW
• Primarily caused by C. albicans and C. parapsilosis
• Common presentation is similarto that of bacterial
sepsis.
The most significant Epidemiologic factors were
 Birth Weight <1000g,
 Presence of central catheter,
 Delay in enteral feeding, and broadspectrum
antibiotic exposure
 The use of H2 blockers orsystemic steroids
CLINICAL FEATURES
• Lethargy
• Feeding intolerance
• Hyperbilirubinemia
• Apnea
• Persistent Hyperglycemia & Thrombocytopenia
• Cardiovascularinstability
• Respiratory distress
• Multi-organ Failure
DIAGNOSIS
 Blood Culture
• Cultures should be obtained through both the central
line catheterand a peripheral vessel - to distinguish
between disseminated infection and catheter-related
candidiasis.
 Urine Culture
• Both fungal culture and fungal staining (KOH
preparation) of urine must be obtained by USG
guided Suprapubic Aspiration (SPA)
• GramStain - VesicularContents /by KOH
Preparations Of Skin Scrapings
Candida albicans on a
culture plate
Pseudohyphae of
Candida albicans on
potassiumhydroxide
(KOH) preparation with
light microscopy
DIAGNOSIS
• Before the initiation of antifungal therapy, CSF
should be obtained forcell count and fungal culture.
Furtherevaluation
• USG abdomen and Brain - Fungal abscess
• Ophthal Assessment- Endophthalmitis
• ECHO - Endocarditis
TREATMENT
Amphotericin B
A polyene, which binds to ergosterol in the fungal cell
membrane leading to cell leakage and death.
Dosage :
•Invasive Candidiasis
Lipid Complex Preparation - 5mg/kg/dose iv infusion
over2 hours O.D
•CNS & Urinary tract Infection
Non-Liposomal Preparation - 0.5 to 1.5 mg/kg/day iv
infusion over2 to 6 hrs.
Contd,..
Duration :
•7-14days fora Negative Blood culture/Catheter
Associated Infection
•Upto 3 weeks if specific end-organ infection is present
Renal Dose Adjustment :
•Alternate day dosing
•Hold the dose for2 to 5days - If Serum creatinine
>0.4 mg/dl from the baseline
Contd,..
Sensitivity :
All common strains except C. lusitaniae, C. glabrata,
and C. Krusei
Adverse Effects :
•Phlebitis at the site of infusion
•Renal toxicity
•Hypokalemia & Hypomagnesemia
•Dose-dependent toxicities -bone marrow suppression
with anemia, thrombocytopenia, and elevated liver
enzymes
Second Line Agent:
Fluconazole
1st
generation Triazole
MOA:
•Inhibits the enzyme 14-alpha-sterol demethylase,
which is necessary forthe production of ergosterol, a
majorcomponent of the fungal cell membrane.
•Added only if initial therapy with amphotericin is not
effective
•Dosage : 12 mg/kg/day Q24H/Q48Hfor2 weeks
•Prophylaxis : 6 mg/kg/day twice weekly for6 weeks
•C. krusei and C. glabrata are frequently resistant
Contd,..
Voriconazole
2nd
generation Triazole
•Broaderspectrum& Increased potency
•Effective in fluconazole-resistant species, but there
are no comparable studies in neonates.
Flucytosine
Nucleoside analogue
•Used in combination with amphotericin B
•Excellent CNS penetration
•Dosage : 50 to 150 mg/kg/day POQ6H
•Only available in enteral form
PREVENTION
• Minimizing use of broad-spectrumantibiotics & H2
Blockers
• Parenteral nutrition and lipid mixtures should be
changed every 24 hours.
• Removal of central catheters when candidemia is
identified
• Prophylactic fluconazole is reserved forELBW
infants in centers with a high incidence of fungal
infection, Routine use is not recommended.
INVASIVE FOCAL INFECTIONS
Focal infection is generally due to seeding of the
individual organ systemfromhematogenous
dissemination.
Involves:
A)UTI
B)CNS INFECTION
C)PERITONITIS
D)ENDOPHTHALMITIS
E)OSTEOARTICULARINFECTIONS
F)ENDOCARDITIS
Candida UTI
Incidence : 0.5 %
Riskfactors : Congenital anomalies of the kidney and
urinary tract, obstruction, urinary stasis, and presence
of an indwelling bladdercatheter
Clinical features : Apnea, bradycardia, glucose
intolerance, & decreased urine output
Diagnosis :
1) Urine Culture –Positive
• > 1000 CFU/mL fora specimen collected by USG
guidance SPA
•> 10,000 CFU/mL in a specimen collected by
catheterization
2) USG KUB
CNS INFECTION
• Incidence : 10%
• Cause : Hematogenous spread of Candida presenting
as meningitis.
• Uncommon Presentation : brain abscesses,
ventriculitis
• Clinical features : Temperature instability,
irritability, poorfeeding, vomiting, respiratory
distress, and apnea
• Complications : Obstructive hydrocephalus
• Diagnosis : CSF analysis/Brain imaging
PERITONITIS
Studies reported to have Spontaneous intestinal
perforation (SIP) is associated with disseminated
candidal infection.
Riskfactors :
•VLBWNeonates
•NEC
Diagnosis :
•Blood/Peritoneal fluid Culture
•USG Abdomen
ENDOPHTHALMITIS
Cause :
•Hematogenous spread of Candida to the eye,
Presenting as Occularcandidiasis.
•Affected neonate is mostly Asymptomatic
•Increased riskof developing ROP
Diagnosis :
Indirect ophthalmoscopy examination
Treatment :
Surgical Intervention – Severe ROP
Focal, glistening, white, infiltrative, often mound-like
lesions on the retinavitreal haziness/snowballs
appearance within the vitreous
OSTEOARTICULAR
INFECTION
Rarely occurs as an isolated event ,
typically occurs because of
disseminated infection
Clinical features :
•Localized erythema/swelling & pain
•Lackof spontaneous movement of the extremity
Diagnosis :
•Depends upon isolating Candida fromeithercultures
of the synovial fluid orbone aspirate
ENDOCARDITIS
It’s the most common complication of candidemia
Riskfactors :
•Central vein catheter
•Cyanotic congenital heart disease
•Prematurity
Diagnosis :
•ECHOto detect thrombi orvegetations
TAKE HOME MESSAGE
• Candida has emerged as a common cause of
infections in infants admitted to the neonatal
intensive care unit (NICU), particularly in VLBW
infants.
• Catheter-related infection is a majorcause of
disseminated systemic infection
• Avoid extensive use of H2 blockers orsystemic
steroids among neonates
• Prophylactic fluconazole is reserved forELBW
infants, not recommended forroutine use.
THANK YOU

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Fungal infection in Neonates

  • 1. FUNGAL INFECTION IN NEONATES DR.RAVI KUMAR 2ND YEARPG DEPT OF PEDIATRICS MGMCRI
  • 2. Discussion • Introduction • Etiology • Epidemiology • RiskFactors • Clinical Manifestations • Diagnosis • Treatment • Prevention
  • 3. Introduction • Among the fungal infections Candida has emerged as an important cause of neonatal infections with significant morbidity and mortality, especially in LBW& ELBWinfants. • Clinical presentations vary fromlocalized skin infections to life-threatening systemic infection
  • 4. Etiology • Candida Infection • Non – Candida Infections - Uncommon Candida • C. Albicans (60%)- most common among Candida spp • C. Parapsilosis. OtherCandida Spp: • C. Tropicalis • C. Lusitaniae • C. Glabrata • C. Krusei
  • 5. Non-candida Spp • Aspergillosis • Zygomycosis • Malassezia Sepsis • Trichosporonosis • Cryptococcosis • Coccidioidomycosis • Blastomycosis • Dermatophytosis.
  • 6. Epidemiology • Candida species are important hospital-acquired pathogens in infants admitted to the NICU. • In VLBWinfants Candida albicans is the third most common cause of LONS. Transmission • Vertical transmission from the motheror • Horizontal transmission from health care workers/ the hospital environment.
  • 7. RiskFactors • Immaturity of host defenses and colonization with Candida before complete establishment of normal intestinal flora probably contribute to the pathogenicity of Candida in the neonate.
  • 8. Clinical Manifestations Various presentations of Candida infections: 1.Mucocutaneous candidiasis 2.Systemic candidiasis 3.Catheter-related infections 4.Focal infection
  • 9. MUCOCUTANEOUS CANDIDIASIS 1) Oral Candidiasis (Thrush) • Irregularwhite plaques • +/- erythematous base on the buccal/lingual mucosa • In breastfed infants - ductal candidiasis in the mother's breast. • Concurrent treatment of both is necessary • Such mother’s are advised to withhold expressed milkuntil treatment has been instituted.
  • 10. white plaques on the innerlip, tongue & Buccal mucosa
  • 11. TREATMENT • Nystatin - oral suspension 1 ml (1 Lakh U/ml) is applied to each side of the mouth Q6Hfor10 to 14 days. • Fluconazole - 6 mg/kg IV/PO once followed by 3 mg/kg IV/PO each day can be used forsevere oral candidiasis if nystatin oral therapy is not effective. • Systemic fluconazole is highly effective in treating chronic mucocutaneous candidiasis in the immunocompromised host.
  • 12. MUCOCUTANEOUS CANDIDIASIS 2) Candida DiaperDermatitis Discrete erythematous papules and plaques over inguinal region with superficial scales, and satellite lesions
  • 13. TREATMENT Effectively treated with Topical agents : •2% nystatin ointment •2% miconazole ointment, •1% clotrimazole cream. •Concomitant treatment with oral nystatin to eliminate intestinal colonization is often recommended •It is reasonable to use simultaneous oral and topical therapy forrefractory candidal diaperdermatitis.
  • 14. MUCOCUTANEOUS CANDIDIASIS 3) Congenital Candidiasis • Generalized eruptions appearon first day of life • 2 to 4 mm erythematous macules /papules that rest upon a 5 to 10 mm erythematous base. • These lesions evolve into pustules, vesicles, oreven bullae. • Riskfactors : Prolonged ROM/Vaginal Candidiasis
  • 15.
  • 16. SEBORRHEIC DERMATITIS • Greasy, yellow plaques on the scalp with some degree of hairloss. • Cause : Presence of Malassezia spp in the oil secretion on the skin • Such lesions are highly prevalent during the first 4 weeks of life Treatment : • Gentle scrubbing of scalp • Vaseline application • Removal of scales using a soft brush • Forextensive cases, topical mild corticosteroid or antifungal is indicated.
  • 18. Systemic Candidiasis • Serious formof nosocomial infection in VLBW • Primarily caused by C. albicans and C. parapsilosis • Common presentation is similarto that of bacterial sepsis. The most significant Epidemiologic factors were  Birth Weight <1000g,  Presence of central catheter,  Delay in enteral feeding, and broadspectrum antibiotic exposure  The use of H2 blockers orsystemic steroids
  • 19. CLINICAL FEATURES • Lethargy • Feeding intolerance • Hyperbilirubinemia • Apnea • Persistent Hyperglycemia & Thrombocytopenia • Cardiovascularinstability • Respiratory distress • Multi-organ Failure
  • 20. DIAGNOSIS  Blood Culture • Cultures should be obtained through both the central line catheterand a peripheral vessel - to distinguish between disseminated infection and catheter-related candidiasis.  Urine Culture • Both fungal culture and fungal staining (KOH preparation) of urine must be obtained by USG guided Suprapubic Aspiration (SPA) • GramStain - VesicularContents /by KOH Preparations Of Skin Scrapings
  • 21. Candida albicans on a culture plate Pseudohyphae of Candida albicans on potassiumhydroxide (KOH) preparation with light microscopy
  • 22. DIAGNOSIS • Before the initiation of antifungal therapy, CSF should be obtained forcell count and fungal culture. Furtherevaluation • USG abdomen and Brain - Fungal abscess • Ophthal Assessment- Endophthalmitis • ECHO - Endocarditis
  • 23. TREATMENT Amphotericin B A polyene, which binds to ergosterol in the fungal cell membrane leading to cell leakage and death. Dosage : •Invasive Candidiasis Lipid Complex Preparation - 5mg/kg/dose iv infusion over2 hours O.D •CNS & Urinary tract Infection Non-Liposomal Preparation - 0.5 to 1.5 mg/kg/day iv infusion over2 to 6 hrs.
  • 24. Contd,.. Duration : •7-14days fora Negative Blood culture/Catheter Associated Infection •Upto 3 weeks if specific end-organ infection is present Renal Dose Adjustment : •Alternate day dosing •Hold the dose for2 to 5days - If Serum creatinine >0.4 mg/dl from the baseline
  • 25. Contd,.. Sensitivity : All common strains except C. lusitaniae, C. glabrata, and C. Krusei Adverse Effects : •Phlebitis at the site of infusion •Renal toxicity •Hypokalemia & Hypomagnesemia •Dose-dependent toxicities -bone marrow suppression with anemia, thrombocytopenia, and elevated liver enzymes
  • 26. Second Line Agent: Fluconazole 1st generation Triazole MOA: •Inhibits the enzyme 14-alpha-sterol demethylase, which is necessary forthe production of ergosterol, a majorcomponent of the fungal cell membrane. •Added only if initial therapy with amphotericin is not effective •Dosage : 12 mg/kg/day Q24H/Q48Hfor2 weeks •Prophylaxis : 6 mg/kg/day twice weekly for6 weeks •C. krusei and C. glabrata are frequently resistant
  • 27. Contd,.. Voriconazole 2nd generation Triazole •Broaderspectrum& Increased potency •Effective in fluconazole-resistant species, but there are no comparable studies in neonates. Flucytosine Nucleoside analogue •Used in combination with amphotericin B •Excellent CNS penetration •Dosage : 50 to 150 mg/kg/day POQ6H •Only available in enteral form
  • 28. PREVENTION • Minimizing use of broad-spectrumantibiotics & H2 Blockers • Parenteral nutrition and lipid mixtures should be changed every 24 hours. • Removal of central catheters when candidemia is identified • Prophylactic fluconazole is reserved forELBW infants in centers with a high incidence of fungal infection, Routine use is not recommended.
  • 29. INVASIVE FOCAL INFECTIONS Focal infection is generally due to seeding of the individual organ systemfromhematogenous dissemination. Involves: A)UTI B)CNS INFECTION C)PERITONITIS D)ENDOPHTHALMITIS E)OSTEOARTICULARINFECTIONS F)ENDOCARDITIS
  • 30. Candida UTI Incidence : 0.5 % Riskfactors : Congenital anomalies of the kidney and urinary tract, obstruction, urinary stasis, and presence of an indwelling bladdercatheter Clinical features : Apnea, bradycardia, glucose intolerance, & decreased urine output Diagnosis : 1) Urine Culture –Positive • > 1000 CFU/mL fora specimen collected by USG guidance SPA •> 10,000 CFU/mL in a specimen collected by catheterization 2) USG KUB
  • 31. CNS INFECTION • Incidence : 10% • Cause : Hematogenous spread of Candida presenting as meningitis. • Uncommon Presentation : brain abscesses, ventriculitis • Clinical features : Temperature instability, irritability, poorfeeding, vomiting, respiratory distress, and apnea • Complications : Obstructive hydrocephalus • Diagnosis : CSF analysis/Brain imaging
  • 32. PERITONITIS Studies reported to have Spontaneous intestinal perforation (SIP) is associated with disseminated candidal infection. Riskfactors : •VLBWNeonates •NEC Diagnosis : •Blood/Peritoneal fluid Culture •USG Abdomen
  • 33. ENDOPHTHALMITIS Cause : •Hematogenous spread of Candida to the eye, Presenting as Occularcandidiasis. •Affected neonate is mostly Asymptomatic •Increased riskof developing ROP Diagnosis : Indirect ophthalmoscopy examination Treatment : Surgical Intervention – Severe ROP
  • 34. Focal, glistening, white, infiltrative, often mound-like lesions on the retinavitreal haziness/snowballs appearance within the vitreous
  • 35. OSTEOARTICULAR INFECTION Rarely occurs as an isolated event , typically occurs because of disseminated infection Clinical features : •Localized erythema/swelling & pain •Lackof spontaneous movement of the extremity Diagnosis : •Depends upon isolating Candida fromeithercultures of the synovial fluid orbone aspirate
  • 36. ENDOCARDITIS It’s the most common complication of candidemia Riskfactors : •Central vein catheter •Cyanotic congenital heart disease •Prematurity Diagnosis : •ECHOto detect thrombi orvegetations
  • 37. TAKE HOME MESSAGE • Candida has emerged as a common cause of infections in infants admitted to the neonatal intensive care unit (NICU), particularly in VLBW infants. • Catheter-related infection is a majorcause of disseminated systemic infection • Avoid extensive use of H2 blockers orsystemic steroids among neonates • Prophylactic fluconazole is reserved forELBW infants, not recommended forroutine use.

Editor's Notes

  1. Maternal vaginal candidal colonization and birth asphyxia are reported risk factors
  2. As sensitivity of a single blood culture is low, repeat blood cultures should be performed to increase the likelihood of detecting disseminated candidiasis.
  3. cephalosporins and carbapenems minimize microbial contamination