Treating Fungal Infections in Premature Babies: A Closer Look at Two Medicines

What a 2025 study by Ibrahim and colleagues found when comparing micafungin with amphotericin B in the NICU

Premature babies who spend weeks in intensive care can develop a serious infection caused by a yeast called Candida, and doctors have long debated which antifungal medicine treats it best. A 2025 study from a hospital in Cairo, Egypt, compared two options in 56 premature babies and found that a newer drug, micafungin, cleared the infection in more babies and was gentler on the kidneys and liver than the older standard drug, amphotericin B [1]. The findings are promising but come from a single small study, so they add to the evidence rather than settle the question.

Why fungal infections happen in the NICU

The neonatal intensive care unit, or NICU, keeps the sickest and smallest newborns alive, but the same tools that save them can also open a door to infection. Very premature babies have thin, immature skin and gut linings, they often need a thin plastic tube (a central line) threaded into a large vein to deliver nutrition and medicine, and they frequently receive antibiotics that unintentionally clear away protective bacteria. In that setting, a normally harmless yeast called Candida — the same family of organism behind common conditions like thrush — can slip from the skin or gut into the bloodstream and travel to organs, including the brain. When it does, it becomes an "invasive" infection that is dangerous and hard to treat. Large international studies have shown that these fungal infections behave differently in newborns than in older children and are closely tied to being born early and to having a central line in place [2]. One particular yeast, Candida parapsilosis, is especially common in the tiniest, lowest-birthweight babies and can spread in a NICU from surfaces and hands [3].

How doctors have treated it, and why the question stayed open

For many years, the go-to treatment was a medicine called amphotericin B. It works against a broad range of fungi, and major infection guidelines still list it as an acceptable choice for newborns [4]. But amphotericin B has real drawbacks in fragile babies: it can strain the kidneys, throw off important minerals in the blood such as potassium and magnesium, and be hard to give smoothly. Over the past two decades, a newer family of antifungal drugs called echinocandins — micafungin is the one used most in newborns — became available. These drugs attack the fungus by weakening its outer wall and tend to be easier on the body. An earlier, larger study comparing micafungin with amphotericin B in infants suggested the two worked about equally well, but micafungin caused fewer side effects [5]. The problem was that the strongest evidence rarely focused on the smallest, most premature babies, and doctors were unsure of the right dose. Because newborns clear the drug from their bodies quickly, and because reaching the brain requires a higher amount, researchers came to favour a higher dose than adults receive.

Understanding the risks helped clarify why the choice matters. Studies of NICU outbreaks pointed to central lines, intravenous nutrition, and prior antibiotics as the main things that set the stage for these infections [6]. A review by medicine regulators pulled together the available evidence supporting micafungin's use in newborns, while noting that important questions about dosing were still unanswered [7]. Separate research showed that giving micafungin at a higher dose was safe in premature babies, including those with infection that had reached the brain [8], and carefully designed studies measured exactly how much of the drug ended up in babies' blood [9]. All of this set up the practical question the Cairo team wanted to answer: in premature babies with a confirmed fungal infection, does high-dose micafungin actually work better than amphotericin B?

What the researchers did

The study was a randomized controlled trial, which means babies were assigned by chance to one treatment or the other so the two groups would be as similar as possible and the comparison would be fair. It took place in a single hospital NICU at Ain Shams University Children's Hospital in Cairo, Egypt, and enrolled babies between September 2022 and September 2023 [1]. The babies were all born before 36 weeks of pregnancy, all had a fungal infection confirmed by a laboratory culture (a test that grows the organism from a sample), and all had already received at least a week of an older antifungal called fluconazole. In other words, these were babies who needed a next step after a first medicine, not babies being treated for the very first time. Fifty-six babies were split evenly: 28 received high-dose micafungin (8 milligrams per kilogram of body weight each day) and 28 received amphotericin B (1 milligram per kilogram each day), each for 14 days [1]. At the end of the two weeks, the doctors repeated the culture to see whether the infection was gone. A "complete cure" meant the culture showed no growth at all [1]. It is worth knowing that, by chance, the babies in the micafungin group were a bit smaller at birth — a difference that would tend to make their treatment look harder, not easier, to succeed [1].

What they found

More babies were cured with micafungin. About 64 out of every 100 babies (64.3%) on micafungin had a completely clear culture after two weeks, compared with about 36 out of every 100 (35.7%) on amphotericin B [1]. Babies on micafungin also needed help with breathing for fewer days (about 13.5 days versus 21.5 days) and needed medicines to support their blood pressure and circulation for fewer days (about 9 days versus 12.5 days) [1]. The number of babies who died was small and the same in both groups — 2 out of 28 in each — so the study did not find a difference in survival [1]. Blood tests told a reassuring story about safety: babies on micafungin showed less strain on the kidneys and liver than those on amphotericin B, and the only downside was a slight, harmless dip in magnesium that did not need treatment [1]. These results fit with a broader analysis that combined many trials in children and newborns [10] and with an earlier study comparing micafungin against a different form of amphotericin [11].

What it means for families — and what still isn't known

If your baby is being treated for a fungal infection in the NICU, this study offers gentle reassurance that micafungin is an effective and well-tolerated option, and it may help explain why a care team chooses it. But it is important to keep the findings in perspective. This was one small study at a single hospital, and the doctors giving the treatment knew which drug each baby received, which can influence results. The babies had already been treated with another antifungal first, so the study really speaks to what to do as a next step, not as the very first treatment. And the particular yeast that showed up most often, C. parapsilosis, is one that micafungin does not always clear as easily, which may explain why some babies still had a different organism growing at the end [1]. For all these reasons, experts view the results as encouraging but not the final word; guideline authors emphasise that the exact type of yeast should guide the medicine chosen [4][12].

If your baby is going through this, there are reasonable questions you can ask the care team: which type of Candida was found and whether it affects the choice of medicine; whether a central line can be removed or replaced, since clearing the source of infection matters as much as the drug itself; and how your baby's kidney and liver blood tests are trending during treatment. These are the same things the medical team is watching, and asking about them can help you feel like a partner in the care rather than a bystander. It is also worth knowing that treatment takes time — a full course in this study lasted two weeks, with a repeat culture at the end to confirm the infection had cleared — so patience is part of the process, and a single early test result does not tell the whole story.

There is also a bigger picture worth mentioning: the best infection is the one that never happens. Researchers continue to study whether giving a preventive antifungal to the highest-risk premature babies, and removing central lines as early as safely possible, can stop these infections before they start [13]. What families can take away is this: fungal infections in premature babies are serious, but they are treatable, and the tools for treating them are steadily improving. Researchers are now working toward larger studies across many hospitals, with attention to which yeast is involved and to how children develop in the years afterward — because the real goal is not just a clear culture, but a healthy child. The Cairo team put it simply, concluding that micafungin worked well and was well tolerated, and calling for larger studies to confirm it [1].

References

  1. Ibrahim MJA, Mohammed Fathy MS, Ghobrial MAT, Mohamed MH. Micafungin versus amphotericin B in treatment of invasive fungal infection in preterm neonates: a randomized control trial. Ital J Pediatr. 2025;51(1):61. doi:10.1186/s13052-025-01852-9 ↩
  2. Steinbach WJ, Roilides E, Berman D, Hoffman JA, Groll AH, Bin-Hussain I, et al. Results from a prospective, international, epidemiologic study of invasive candidiasis in children and neonates. Pediatr Infect Dis J. 2012;31(12):1252–1257. doi:10.1097/INF.0b013e3182737427 ↩
  3. Clerihew L, Lamagni TL, Brocklehurst P, McGuire W. Candida parapsilosis infection in very low birthweight infants. Arch Dis Child Fetal Neonatal Ed. 2007;92(2):F127–F129. doi:10.1136/adc.2006.097758 ↩
  4. Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr KA, Ostrosky-Zeichner L, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016;62(4):e1–e50. doi:10.1093/cid/civ933 ↩
  5. Benjamin DK Jr, Kaufman DA, Hope WW, Smith PB, Arrieta A, Manzoni P, et al. A phase 3 study of micafungin versus amphotericin B deoxycholate in infants with invasive candidiasis. Pediatr Infect Dis J. 2018;37(10):992–998. doi:10.1097/INF.0000000000001996 ↩
  6. Garzillo C, Bagattini M, Bogdanović L, Di Popolo A, Iula VD, Catania MR, Zarrilli R. Risk factors for Candida parapsilosis bloodstream infection in a neonatal intensive care unit: a case-control study. Ital J Pediatr. 2017;43(1):10. doi:10.1186/s13052-017-0332-5 ↩
  7. Taormina G, Gopinath R, Moore J, Yasinskaya Y, Colangelo P, Reynolds K, Nambiar S. A regulatory review approach for evaluation of micafungin for treatment of neonatal candidiasis. Clin Infect Dis. 2021;73(12):2335–2340. doi:10.1093/cid/ciab025 ↩
  8. Auriti C, Falcone M, Ronchetti MP, Goffredo BM, Cairoli S, Crisafulli R, et al. High-dose micafungin for preterm neonates and infants with invasive and central nervous system candidiasis. Antimicrob Agents Chemother. 2016;60(12):7333–7339. doi:10.1128/AAC.01172-16 ↩
  9. Leroux S, Jacqz-Aigrain E, Elie V, Legrand F, Barin-Le Guellec C, Aurich B, et al. Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial. Br J Clin Pharmacol. 2018;84(9):1989–1999. doi:10.1111/bcp.13628 ↩
  10. Chen YH, Cheng IL, Lai CC. Echinocandins vs. amphotericin B against invasive candidiasis in children and neonates: a meta-analysis of randomized controlled trials. Int J Antimicrob Agents. 2019;53(6):789–794. doi:10.1016/j.ijantimicag.2019.02.019 ↩
  11. Queiroz-Telles F, Berezin E, Leverger G, Freire A, van der Vyver A, Chotpitayasunondh T, et al. Micafungin versus liposomal amphotericin B for pediatric patients with invasive candidiasis: substudy of a randomized double-blind trial. Pediatr Infect Dis J. 2008;27(9):820–826. doi:10.1097/INF.0b013e31817275e6 ↩
  12. Viscoli C, Bassetti M, Castagnola E, Cesaro S, Menichetti F, Ratto S, Giacobbe DR. Micafungin for the treatment of proven and suspected invasive candidiasis in children and adults: findings from a multicenter prospective observational study. BMC Infect Dis. 2014;14:725. doi:10.1186/s12879-014-0725-7 ↩
  13. Ferrando G, Castagnola E. Prophylaxis of invasive fungal infection in neonates: a narrative review for practical purposes. J Fungi (Basel). 2023;9(2):164. doi:10.3390/jof9020164 ↩