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Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Sir Ganga Ram Hospital, New Delhi
9810146581, [email protected]
13/12/2019: NEOCON 2019; HYDERABAD
Fungal infections in Neonates:
How do I treat
SGRH
PHOT
O
• MBBS, MD, DNB
• DNB PEDIATRICS, NEONATOLOGY and GYNAE & OBS TEACHER
• TAKES CARE OF 40 BEDDED NICU; 1200 ADMISSIONS FOR LAST 20
YEARS
• 32 INDEXED PUBLICATIONS
• PRESIDENT NORTH DELHI IAP BRANCH
• PAST NNF DELHI CHAPTER GENERAL SECRETARY
• SPEAKER INTEREST: NEONATAL INTENSIVE CARE, NEONATAL AND
PEDIATRIC NUTRITION, IMMUNIZATION
Which neonatal population gets
fungal infections?
Systemic infection: VLBW; ELBW even more
likely
Oral thrush/Fungal diaper dermatitis: Term babies;
preterm babies after discharge
Goals of management?
Adequate treatment
Supportive
Antifungal drugs
Prevention
General measures
Fluconazole prophylaxis in ELBW/VLBW
infants
Oral or diaper dermatitis: does it
always require treatment
No
In healthy term infants who lack symptoms, are feeding well,
and are at low risk of invasive candidiasis
National Institute for Health and Care Excellence guidelines
suggest treatment
the symptoms are causing pain to the woman or the baby or
feeding concerns to either
Nystatin/Miconazole (DAKTARIN oral gel) /Clotrimazole
If no response
Fluconazole
3mg/kg OD for 7 days
When is treatment always required??
Invasive fungal infections
Congenital cutaneous candidiasis
Retrospective case series of 21 infants with CCC (18
preterm and 3 term; mean birth weight 950 g)
20 treated within 48 hrs of rash; 1 not treated
1/20 got infection; 1/1 got disseminated infection
Kaufman DA, Coggins SA, Zanelli SA, Weitkamp JH. Congenital Cutaneous Candidiasis:
Prompt Systemic Treatment Is Associated With Improved Outcomes in Neonates. Clin
Infect Dis 2017; 64:1387
Management principles for invasive
fungal infections?
Evaluation to assess the extent of dissemination
urinary tract, CNS, eyes, heart valves, bone, or
joints
Removal of any source of infection (e.g, central
venous catheter [CVC], urinary catheter)
Drugs
Amphotericin B is the preferred drug for treatment
of most systemic neonatal candidal infections
Is removing central line evidence
based?
Yes
Retrospective study (104 neonates)
Early removal (within 3 days of the first positive blood
culture)
Associated with shorter duration of candidemia; 3vs 6
Lower mortality (0 versus 39 percent)
Karlowicz MG, Hashimoto LN, Kelly RE Jr, Buescher ES. Should central
venous catheters be removed as soon as candidemia is detected in
neonates? Pediatrics 2000; 106:E63.
How to choose antifungal drugs in
invasive fungal infections?
Amphotericin-B
As soon as fungal
growth positive
Monotherapy
1-1.5mg/kg/d
Very less side effects
Fluconazole
Only after sensitivity
documented
Feeding well, not toxic
Follow up therapy
Uncomplicated UTI
12 mg/kg/d
Very less side effects
Time to positivitySGRH Data
Gram negative organisms 0.5 days
CONS / Staph aureus 0.7 days
Candida 2.3 days
Flow
chart
for
Candida
UTI
Urine culture positive
Blood culture
Positive
Treat as systemic infection
Negative
No fungal mass on USG abdomen
Not toxic, feeding well
yes
Oral Fluconazole
no
Amphotericin B or IV fluconazole for 14 days or till resolution of mass
Flow chart
for
Candida
Meningitis
CSF culture positive or CSF cytology/bio positive with blood culture positive,
Monotherapy with Amphotericin-B
Removal of shunt if any
Clinical improvement
Continue for 21 days
Clinically unstable
Repeat CSF still positive
Add Oral Flucytosine 25mg/kg/dose every 6 hrly
MRI
Continue till all signs/MRI fungal shadows persist
Flow chart
for
Invasive
Candida
Infections
Blood culture positive; End organ evaluation normal
Monotherapy with Amphotericin-B; Removal of Central line if possible
Clinical improvement
Repeat blood culture after 7 days
Negative
2 weeks more or till resolution of imaging
findings
Positive
Add Fluconazole if sensitive; otherwise Caspofungin
Flow chart
for
Invasive
Candida
Infections
Blood culture positive; End organ evaluation abnormal
Monotherapy with Amphotericin-B; Removal of Central line if possible
Clinical improvement
Repeat blood culture after 7 days
Negative
3-5 weeks more or till resolution of imaging findings
Positive
Add Fluconazole if sensitive; otherwise Caspofungin
Surgical option may have to be exercised
When can a new PICC be inserted?
New PICC should ideally be inserted after documentation of
clearance of Candida from blood with at least 3 negative cultures
within first 3 days of therapy or
Two or more than 2 negative cultures after 4 days of antifungal
treatment
Amphotericin-B
Does the dose needs to be modified with pre-
existing renal disease
No
Does the dose needs to be modified with renal
disease appearing after start of drug
Yes (50%)
Any Candida strains resistant to it?
Candida lusitaniae
Side effects of Ampho-B in neonates more or
less compared to older children or adults?
Less
Hypokalemia, renal tubular dysfunction, bone
marrow toxicity, hypomagnesemia, liver enzymes
raised
Infrequent, dose dependent, and resolve with
cessation of the drug.
Plain vs Liposomal Ampho-B
Plain except
develop intolerant infusion-related reactions or
renal dysfunction during standard amphotericin
B administration.
The lipid formulations should not be used in
patients with Candida urinary tract infections
(UTIs).
Is it just the cost or evidence also
against liposomal ampho-B?
Multicenter retrospective review of 730 infants
Multivariate analysis showed higher mortality with
liposomal
[OR] 1.96, 95% CI 1.16-3.33)
Ascher SB, Smith PB, Watt K, et al. Antifungal therapy and outcomes in
infants with invasive Candida infections. Pediatr Infect Dis J 2012; 31:439.
Disadvantages of Fluconazole?
Certain species are resistant
Krusei, Glabrata
Resistance increasing esp after prophylaxis
Clinical trials using as first line drugs: few with
high mortality rates
Newer Antifungals
Reserved for difficult cases only
Voriconazole
Not many trials in neonates
Usual reported dose: 12 to 20 mg/kg/day divided
every 8 to 12 hours
Caspofungin
Very well tolerated
2 mg/kg/dose once daily
Any role of empirical ampho-B
????
Outcome
Guarded
Mortality: 20-40% in ELBW
Survivors of neonatal candidemia, especially in
those with central nervous system involvement,
are at risk of long-term neurodevelopmental
impairment
Antifungal prophylaxis
No routinely provide antifungal prophylaxis for all
preterm infants
Antifungal prophylaxis is reserved for ELBW
NICUs with a high baseline rate of systemic fungal
infection (ie, greater than 5 to 10 percent)
Consistent with American Academy of Pediatrics and
the Infectious Diseases Society of America
recommendation
Antifungal prophylaxis
Fluconazole
within the first 48 to 72 hours after birth
3 mg/kg per dose given intravenously twice a week
for four to six weeks or until the infant no longer
requires intravenous access
Evidence
2015 meta-analysis of 10 trials (including 1371 very
preterm or VLBW infants)
Reduced the incidence of invasive fungal infection
compared with placebo or no drug (6.2 versus 15.7
percent; RR 0.43, 95% CI 0.31-0.59)
Effect on mortality was not statistically significant
(12.7 versus 17.3 percent; RR 0.79, 95% CI 0.61-
1.02)
Take Home Messages
Disease of high morbidity and mortality
Fluconazole prophylaxis in ELBW
Ampho B (plain) drug of choice
Dose of fluconazole going up; 12mg/kg/day
PICC removal helps
Candida non albicans more common now
Prevention holds the key
Antibiotics are not with out harm
Dr Pankaj Garg
Senior Consultant, Department of Neonatology
Sir Ganga Ram Hospital, New Delhi
9810146581, [email protected]
13/12/2019: NEOCON 2019; HYDERABAD
Fungal infections in Neonates:
How do I treat
SGRH