Key messages
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Newborn babies sometimes get infections caused by fungi entering the baby's bloodstream or deep body tissues (invasive fungal infections). It is unclear if one type of medicine that kills the fungi or stops it growing (antifungal treatment) is better than another antifungal treatment in reducing the risk of death, having to stop treatment due to unwanted side effects, or how long the baby stays in hospital. However, this conclusion is based on a few small studies.
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Large, well-designed studies are needed to evaluate the benefits and potential harms of antifungal medicines to treat invasive fungal infection in newborn babies.
What is an invasive fungal infection?
An invasive fungal infection is when fungi enter the baby's bloodstream or deep body tissues. Invasive fungal infections are usually caused by Candida, which is a yeast infection. Invasive fungal infections are serious and are the major cause of death and serious illness in babies born early (preterm).
How are invasive fungal infections treated?
Invasive fungal infections are commonly treated with a variety of medicines that kill fungi or stop fungi growing (antifungal medicines), such as:
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polyenes (e.g. amphotericin B);
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azoles (e.g. fluconazole);
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echinocandins (e.g. micafungin, caspofungin); and
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antimetabolites (5-fluorocytosine).
What did we want to find out?
We wanted to find out if any particular antifungal medicine or combination of antifungal medicines was better to improve:
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the risk of the baby dying (for any reason) before leaving the hospital;
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development of the baby's nervous system (neurodevelopment) by the time the baby is two years old;
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the risk of having to give a higher dose of the antifungal medicine, or adding another antifungal medicine, because the infection is not getting better or is worsening;
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how long babies stay in hospital; and
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unwanted or harmful effects of antifungal medicines (meaning the medicine has to be stopped).
What did we do?
We searched for studies that investigated antifungal medicines (or combinations of antifungal medicines) in newborn babies, either born early (preterm) or at the usual time (full-term). We compared and summarised the results of the studies and rated our confidence in the evidence, based on factors such as study methods and sizes.
What did we find?
We found six studies that involved 229 newborn babies with invasive fungal infections. One study only included preterm babies and the others included both preterm and full-term babies. One study compared fluconazole with amphotericin B; two studies compared micafungin with amphotericin B; two studies compared caspofungin with amphotericin B; and one study compared micafungin with fluconazole.
Main results
It is unclear if one antifungal treatment is better than another antifungal treatment at reducing the risk of a baby dying in hospital or having to stop the medicine due to its unwanted or harmful side effects.
It is unclear if fluconazole or micafungin, compared to amphotericin B, may reduce the number of days that newborn babies with invasive fungal infections have to stay in hospital.
What are the limitations of the evidence?
We are not confident in the evidence. This is because some studies had limitations in the way they were conducted. For example, the researchers were aware of the treatment received by the babies, which could have influenced the results. In addition, the evidence does not cover all the outcomes we were interested in. There were not enough studies to be certain about the results and the studies were very small.
How up to date is this evidence?
This review updates our previous review first published in 2004 and updated in 2012. The evidence is up to date to November 2025.
Read the full abstract
Background
A variety of antifungal drugs, drug preparations and drug combinations are available to treat newborn infants with suspected or confirmed invasive fungal infection. There is a need to assess their relative merits.
Objectives
To evaluate the benefits and harms of treatment with one antifungal drug or drug combination or preparation versus another on mortality and morbidity in newborn infants with suspected or confirmed invasive fungal infection.
Search strategy
We searched CENTRAL, MEDLINE, Embase, Emcare, and three trial registers up to 14 November 2025; and CINAHL to June 2025. We searched reference lists of studies and reviews.
Selection criteria
Randomised and quasi-randomised control trials comparing one antifungal agent or combination of agents with another in newborn infants with suspected or confirmed invasive fungal infection.
Data collection and analysis
We extracted the data using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using risk ratio and risk difference.
Main results
We identified only one small trial in which 24 newborn infants participated. This trial compared the use of fluconazole versus amphotericin B (plus 5-fluorocytosine if fungal meningitis present). The trial did not detect a statistically significant effect on mortality (risk ratio 0.73; 95% confidence interval 0.26 to 2.05).
Authors' conclusions
The evidence is very uncertain about the effect of fluconazole or micafungin on death before hospital discharge, adverse reactions attributed to the antifungal agent that result in discontinuation, or length of hospital stay, when compared to amphotericin B.
The evidence is very uncertain about the effect of caspofungin on death before hospital discharge, or adverse reactions attributed to the antifungal agent that result in discontinuation, when compared to amphotericin B.
The evidence is very uncertain about the effect of micafungin on death before hospital discharge or adverse reactions attributed to the antifungal agent that result in discontinuation, when compared to fluconazole.
Large RCTs with low risk of bias are required to compare antifungal drugs, drug preparations or drug combinations for treating newborn infants with invasive fungal infection. Future RCTs should stratify participants by gestational age and should also measure antifungal resistance and long-term neurodevelopmental outcomes.
Funding
This Cochrane review had no dedicated funding.
Registration
Protocol (2002) DOI: 10.1002/14651858.CD003953
Original review (2004) DOI: 10.1002/14651858.CD003953.pub2
Review update (2012) DOI: 10.1002/14651858.CD003953.pub3
