Suspected ( but unproven ) Invasive Candida Infection - Guideline for the Management of

Publication: 01/03/2009  
Last review: 13/07/2018  
Next review: 13/07/2021  
Clinical Guideline
CURRENT 
ID: 1548 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2018  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for the Management of Suspected (but unproven) Invasive Candida Infection

Summary
Suspected ( but unproven ) Invasive Candida Infection

Diagnostic criteria
Criteria for use of guidelines

  • Neonatal patients either at risk of or diagnosed with Suspected (but unproven) invasive Candida infections in neonates

Investigations
See main guideline

Treatment
See main guideline

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Background

Invasive fungal infection cause a significant disease burden in NICUs worldwide, with mortality rates recorded as high as 44%.1The most common fungi causing invasive infection in neonates are Candida species, which account for  up to 12% of late-onset sepsis in very low birth weight (VLBW) infants (<1500g).2 Non-specific clinical features, poor sensitivity of diagnostic tests, and late recognition mean that at the time of diagnosis invasive fungal infection is often advanced. VLBW neonates are at risk of invasive fungal infection because of their immature immune system and the invasive supportive care they receive. Other risk factors include prior exposure to broad spectrum antibiotics, indwelling central venous catheters, parenteral nutrition and corticosteroid therapy.4

The antifungal treatment regimens used in the United Kingdom are similar to those reported from North America.5 At present there is insufficient evidence to favour one antifungal agent over another for treating VLBW infants with invasive fungal infection.6 Currently the clinical choice of therapy may be affected by concerns about the risk of toxicity associated with the various drugs. For example, in some patients, evidence exists that renal toxicity is higher with conventional amphotericin B than with lipid complex formulations or with azole drugs. However, there are only a few observational data on the relative risks of toxicity of antifungal drugs in VLBW infants.5

Studies have shown that colonisation with Candida spp. is an important risk factor for subsequent infection.7 Prophylaxic nystatin has been shown to reduce the incidence of colonisation and invasive Candida infection in this population.3 The infectious disease Society of America (IDSA) has published a consensus statement on the treatment of candidiasis.7

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Clinical Diagnosis

Suspect if any risk factors are present such as VLBW baby with indwelling catheters. If an “at risk” infant is clinically septic despite 48 hours IV antibiotics AND the Blood cultures are negative and the baby has thrombocytopenia or a significant or increasing CRP then investigate and treat for fungal infection.

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Investigation
  • Repeat Blood Cultures (peripheral and from any all central lines)
  • Urine culture (SPA)
  • CSF culture
  • Renal USS
  • Echocardiogram
  • Cranial USS

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Treatment
  • First line: Fluconazole electronic Medicines Compendium information on Fluconazole PO/IV. Consider changing to Ambisome if non-albicans Candida species is/has been isolated or no improvement by 72 hours.
  • Continue empirical treatment for 2 weeks in the absence of any other explanation for the baby’s condition.
  • Fluconazole electronic Medicines Compendium information on Fluconazole should be used only where diagnoses of Candida meningitis or endocarditis are considered unlikely or have been excluded by appropriate investigations. If these diagnoses are under consideration, Ambisome should be used.
  • NOTE: The majority of these infants will not have fungal infection. Continue to search for and treat infection caused by other organisms.

Table of drug doses

Drug

Dose

Administration

Monitoring

Adverse Effects

Fluconazole electronic Medicines Compendium information on Fluconazole 
Treatment (PO/IV)(12,14)
<2 weeks
12mg/kg/dose daily every 3rd day
2-4 weeks
12mg/kg/ dose daily every 2nd day
>4 weeks
12mg/kg/
dose once daily
Discuss with pharmacist if there is renal impairment

Slow infusion over 10-30 mins or use oral suspension. There is no need for a dose conversion.

LFTs
Potassium
FBC

Diarrhoea, skin rash.
Deranged LFTs, usually transient.
Hypokalaemia
Anaemia
Low platelets

Contraindications to Fluconazole electronic Medicines Compendium information on Fluconazole:

  • Hypersensitivity to azole compounds.
  • Co-administration of Cisapride or terfenadine
    Interactions:
  • Fluconazole electronic Medicines Compendium information on Fluconazole enhances plasma levels of phenytoin, theophylline, zidovudine and midazolam
    Side effects:
  • Stevens Johnson syndrome / Toxic epidermal necrolysis
  • Elevated liver enzymes (in 5 - 7%)
  • Occasional eosinophilia, anaemia, thrombocytopenia and hypokalaemia.

Drug

Dose

Administration

Monitoring

Adverse Effects

Ambisome(12,13,15, 16)

Initial test dose 100 micrograms/kg then:
1mg/kg dose once daily, increasing by 1mg/kg/day to 3mg/kg once daily.

Slow iv infusion over 30-60 minutes

Renal function
Potassium
Magnesium
Phosphate
LFTs
Avoid other nephrotoxic drugs if possible

Acute infusion related reactions: fever, chills, vomiting, tachypnoea, GI effects.
Nephrotoxicity
Hypokalaemia
Hypomagnesaemia
Anaemia

For interactions and side effects of ambisome see BNF 2009

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Provenance

Record: 1548
Objective:

Aims
• To improve the diagnosis, investigation, management and prevention of Suspected (but unproven) invasive Candida infections in neonates

Objectives
• To provide evidence-based recommendations for appropriate investigation of Suspected (but unproven) invasive Candida infections in neonates
• To provide evidence-based recommendations for appropriate antimicrobial therapy of Suspected (but unproven) invasive Candida infections in neonates
• To recommend appropriate dose, route of administration and duration of antimicrobial agents.
• To advise in the event of antimicrobial allergy.
• To set out criteria for referral for surgery or specialist input.

 

Clinical condition:

Candida Infections in neonates

Target patient group: Neonates
Target professional group(s): Secondary Care Doctors
Pharmacists
Adapted from:

Evidence base

  1. Healy et al. Fluconazole Prophylaxis in Extremely Low Birth Weight Neonates Reduces Invasive Candidiasis Mortality Rates Without Emergence of Fluconazole-Resistant Candida Species. Pediatrics 2008;121;703-710
  2. Stoll et al. Late-onset sepsis in VLBW neonates: the experience of the NICHD Neonatal Research Network. Pediatrics 2002; 110(2);285-291
  3. Manzoni et al. A Multicentre, Randomized Trial of Prophylactic Fluconazole in Preterm Neonates. N Engl J med 356;24: 2483-249
  4. Kicklighter et al. Fluconazole for Prophylaxis Against Candidal Rectal Colonisation in the VLBW Infant. Paediatrics 2001;107:293-8
  5. L Clerihew, T L Lamagni, P Brocklehurst, and W McGuire. Invasive fungal infection in very low birthweight infants: national prospective surveillance study. Arch. Dis. Child. Fetal Neonatal Ed 2006
  6. Clerihew L, McGuire W. Systemic antifungal drugs for invasive fungal infection in preterm infants. Cochrane Database Syst Rev 2004;1
  7. Pappas PG et al. Guidelines for the treatment of candidiasis.
  8. Makhoul et al. Review of 49 Neonates with acquired fungal sepsis: further characterization. Paediatrics 2001; 107:61-66
  9. Rex JH, Walsh, TJ, Sobel JD. Practice guidelines for the treatment of candidiasis.
  10. Karlowicz, MG et al. Should central venous catheters be removed as soon as candidaemia is detected in neonates? Pediatrics 2000;106(5) e63
  11. McGuire W, Clerihew L, Austin N. Prophylactic intravenous antifungal agents to prevent mortality and morbidity in very low birth weight infants (Cochrane review). In The Cochrane Library, issue 1, 2003. Oxford: Updated software.
  12. F Adler-Shohet, H Waskin, and J M Lieberman. Amphotericin B lipid complex for neonatal invasive candidiasis. Arch. Dis. Child. Fetal Neonatal Ed., 2001; 84: 131 - 133. 
  13. N. Linder, G. Klinger, I. Shalit, I. Levy, S. Ashkenazi, G. Haski, O. Levit, and L. Sirota
    Treatment of candidaemia in premature infants: comparison of three amphotericin B preparations. J. Antimicrob. Chemother. 2003; 52(4): 663 - 667. 
  14. D. Kaufman and K. D. Fairchild. Clinical Microbiology of Bacterial and Fungal Sepsis in Very-Low-Birth-Weight Infants. Clin. Microbiol. Rev.2004; 17(3): 638 - 680. 
  15. H Smith and P Congdon. Neonatal systemic candidiasis. Arch. Dis. Child. 1985; 60: 365 - 369.
  16. Huttova M, Hartmanova I, Kralinsky K, et al. Candida fungemia in neonates treated with fluconazole: report of forty cases, including eight with meningitis. Pediatr Infect Dis J.1998; 17 :1012 –1015
  17. L Clerihew, T L Lamagni, P Brocklehurst, and W McGuire. Candida parapsilosis infection in very low birthweight infants. Arch. Dis. Child. Fetal Neonatal Ed.2007; 92(2): 127 - 129. NB – This last article states that C. parapsilosis is best treated with Ambisome but this doesn’t conform to previous guidelines??

Evidence levels:
A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
B. Robust experimental or observational studies
C. Expert consensus.

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

Related information

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