Proper management of fungal infections in neonates especially preterm is crucial in proper outcome in NICUs worldwide. The wide spread of antibiotics has led to the flourishing of fungal species in preterm neonates. Researching the effectiveness of the different antifungal drugs proposed was the target of our study, and we studied the effectiveness of micafungin in comparison to amphotericin B in the management of invasive fungal infections in preterm neonates. In our study Micafungin group showed significant increased percentage of complete cure of neonates with fungal culture changing to negative after fourteen days of treatment, compared to Amphotericin B group, 18 (64.3%) vs 10 (35.7%) respectively and a decreased percentage of in complete cure compared to Amphotericin B, 10(35.7%) vs 18(64.3%) respectively with p-value 0.030. Amphotericin B was not able to attain complete cure after 14 days of treatment with a persistent growth of fungal species in fungal culture after 14 days of treatment.
Similar results were reported by a previous study (1) that reported the effectiveness of Micafungin in altering negative fungal culture at 5.5 days ranging (1-11days). Duration was extended in candida glabarata, meningitis and in patients with candida albicans urinary sepsis to 9 days.
In previous prospective, observational studies, it has been reported that patients under the age of 18 with invasive candidiasis have achieved favorable treatment outcomes and high rates of survival with micafungin (9)(10). Success rates observed in neonates are comparable to those determined in pediatric research. On the other hand, an illustration provided by the researchers documented comparable rates of treatment efficacy after Micafungin at a dose (2 mg/kg), and liposomal amphotericin B (3 mg/kg) in patients < 16 years of age with Invasive candidiasis (11).
According to the results we reached in our study we recommend completion of fungal treatment with Micafungin for at least 14 days to attain fungal eradication in low resources countries where fungal culture will not be readily available to be requested as frequently as needed.
In our study as regarding the different candida species in Micafungin group, (65.2%) that had original candida albicans growth in fungal culture and received Micafungin had total eradication of this organism in the blood culture after 14 days of taking treatment, on the other hand only (40%) of the patients who received Amphotericin B had complete eradication from candida albicans in their fungal culture.
Only (17.4%) that had original candida albicans growth in their fungal culture, showed persistence of the organism after 14 days of treatment with Micafungin, as opposed to a higher percentage of (40%) of the patients that similarly showed persistence of the candida albicans species in Amphotericin B group.
8.7% of patients who had original candida albicans growth in their fungal culture and received Micafungin for 14 days, developed candida non albicans in their fungal blood culture after 14 days. We couldn’t estimate the exact time when the patient developed the non albicans species infection, so effectiveness of the drug cannot be assessed according to this issue on its own.
(60%) of patients with original candida non-albicans growth in their fungal culture and received Micafungin had total eradication of the organism after 14 days of taking the treatment, on the other hand a less percentage of (33.3%) of the patients who received Amphotericin B had total eradication from candida non-albicans in their fungal culture.
(40%) of patients with original candida non-albicans growth in their fungal culture and received Micafungin for 14 days still showed growth for candida non-albicans in their fungal culture, which is similar to (44.5%) of patients who received Amphotericin B and still had persistence of Candida non-albicans in their fungal culture after 14 days of treatment. the previous comparisons showed a clear difference in percentages but did not mount statistical significance owing to the small sample size used. Further studies are recommended to be done to further tackle the eradication of specific fungal species in each category in neonates.
Similarly, Benjamin et al., (12) reported, in his study that was done on 20 infants who received Micafungin and 10 infants who received Amphotericin B deoxycholate for at least 21 days and fungal culture was done one week after the last dose, that complete eradication was observed in 11 (55%) of patients who received Micafungin and 8(80%) who received Amphotericin B deoxycholate. Candida infections that persisted were due to Candida. parapsilosis in 2 Micafungin-treated infants and Candida. glabrata and Candida. albicans in neonates with amphoteric acid deoxycholate (n = 1 for each) was recorded. In fact. one-fourth of invasive fungal infection cases in very low birthweight neonates (less than 1500 g) are attributable to parapsilosis (14). Among non-albicans Candida species, parapsilosis has become the most prevalent in neonatal invasive candidiasis (15).
In our study, we used high dose of micafungin in neonates due to high clearance (13) and high volume of distribution in neonates as presented by previous studies (3).
It is noted that there is an uncertainty to the clinical applicability of echinocandins in the treatment of Candida parapsilosis as it needs a mean inhibitory concentration that is greater in comparison to other Candida species (16).
In our study Micafungin group did not show any abnormalities in liver or kidney function but they showed significantly lower magnesium concentration compared to Amphotericin B but the drop in magnesium showed no signs or symptoms and did not need any correction. Creatinine and ALT concentrations were within normal acceptable range indicating no affection or alteration with the use of the Micafungin.
On the other hand, Amphotericin B patients had significant elevation of their renal function compared to Micafungin group in our study.
In agreement with our results Arıkan et al., (1) also reported no increase in liver function test or renal function test on using Micafungin. Conversely, Previous study have reported elevation in liver, renal functions, and electrolytes in Micafungin group. In a study by Benjamin et al., (12) the authors reported significant elevation in bilirubin and liver enzymes in Micafungin group than Amphotericin B group. In addition, there was a significant drop in potassium and magnesium levels which needed to be treated by giving the respective deficit of potassium and magnesium. This study was in infants from (2-120 days) who received Micafungin at 10mg/kg/day for a minimum of 21 days and maximum of 28–42 days and the basal liver function of the patients was not known which may explain the elevation of liver function after the use of micafungin.
In our study patients who received Micafungin did not develop any complication, indicating the safety of the use of Micafungin with no emergence of complications.
In our study as part of improvement of the patient general condition patients in Micafungin group has a significant decrease of duration of respiratory support and were successfully extubated earlier than the patients in Amphotericin B group. Also, the positive effect in circulation was seen in the readiness to withdraw inotropic drugs and short duration of total inotrope used indicating the efficacy of Micafungin in the management of invasive fungal infections and improvement of patients' overall health.
Although patients in micafungin group in our study showed short duration of respiratory and circulatory support, this was not interpreted in the length of hospital stay and age at discharge. It has to be noted that the patients included in the study had other comorbid conditions that could have prolonged their hospital stay until everything was completely managed and treated.
To the best of our knowledge hospital stay and age of discharge were not researched in other studies researching the effect of Micafungin in neonates.