ABSTRACT
Candida species are the leading cause of invasive fungal infections in hospitalized children. Colonization by Candida spp. is' almost always the first step in the development of invasive candidiasis. Preterm neonates in NICUs are at high risk for severe fungal infections. Early-onset neutropenia is a well-known risk factor for bacterial sepsis in preterm neonates. The aim of this case control study was evaluation of the role of early onset neutropenia as a risk factor for Candida colonization in preterm very low_ birth weight neonates in NICU, the current role of granulocyte colony-stimulating factor in treatment of these conditions and to screen the antifungal susceptibility of the isolated Candida spp to help management of emerging fungal infections. Forty four very low birth weight" [VLBW] neonates were enrolled in this study. ·They were classified into two groups. Group I: twenty two VLBW neonates [<1500gm] with early onset neutropenia [EON] in the 1st week of life and group II: twenty two matched VLBW neonates without EON as a control group. Group I was further divided into: group IA: Eleven neonates received recombinant granulocyte colony stimulating factor [G CSF] for 3 consecutive days plus routine therapy and group IB: Eleven neonates received routine therapy. Surveillance microbiological swabs from ear canal, oropharyngeal secretions, perianal area and rectum, urine and blood in the 1st and 2nd weeks were collected and cultured according to standard methods. Colonies identified as Candida by colonial morphology on sabouraud dextrose agar and CHRO Magar candida media. All isolated strains were subjected to broth microdilution assays to detect MIC for voriconazole, fluconazole, Iitraconazole, and amphotericin B with calculation of MIC50 and MIC90 for the isolated strains. The study revealed a significant difference of colonization by Candida spp in neutropenic group I as 9 cases out of 22 patient in group I were colonized while only 3 cases out of 22 patient in group II were colonized by Candida spp. [P value 0. 04]. Out of 220 samples cultured from each group, Candida spp were significantly isolated from group I [26] in comparison to group II [JO] [P value 0.05]. C. albicans was the most commonly isolated Candida species followed by C. tropicalis, then C. glabrata. There was a good therapeutic effect of rhG-CSF on intensity of colonization as three cases with high grade colonization in the 1st week improved to low grade colonization in the second week. Treatment with rhGCSF significantly improved absolute neutrophilic count in group IA receiving rhGCSF than group IB [conventional treatment]. Among all isolates of Candida spp, the highest MIC 50 and MIC 90 were for fluconazole [4 and 64 microglml respectively]. The lowest MIC50 and MIC90 were for voriconazole [0.06and0.5 microg/ml]. C. albicans was the most susceptible species to voriconazole [MIC50, 0.03 microg/ml while MIC90, 0.06 microg/ml]. C. tropical is the least susceptible to voriconazole [[MIC50, 0.5 microg/ml while MIC90, 2 microg/ml]. Amphotericin B MICs show a very narrow range [0.25-1 microglml]. Isolated strains were all susceptible to amphotrocinB. As regards to azoles tested, isolated strains were most sensitive to voriconazole [97.2%], followed by Iitraconazole [88.9%] and fluconazole [83.3%] respectively. This study concludes that early onset neutropenia is an independent risk factor for Candida colonization and treatment with rhGCSF corrects ANC sooner and decreases the intensity but fails to completely clear Candida colonization so it recommends proper antenatal and post-natal care to decrease other risk factors of pre-maturity and Candida colonization. This study also concludes that Candida spp isolated is still sensitive to amphotericin B. But resistance to azole antifungal drugs is an emerging problem so it recommends further studies to evaluate the antifungal resistance