الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 204 |  |  |
| | | from | 204 | | |
Abstract
Fungal infections have become an increasingly significant cause of neonatal morbidity and mortality, especially in premature and very low birth weight infants. Morbidity and mortality is exceptionally high in this group of low birth weight neonates because they are particularly susceptible to invasive fungal infections. Invasive infection is defined as a systemic infection of either vital organs or normally sterile body fluids, such as blood or cerebrospinal fluid (CSF).The diagnosis of fungal infection should be considered in any neonate with sepsis and should be either confirmed or excluded. These infections are often severe, rapidly progressive, difficult to diagnose and refractory to therapy.
Risk factors for fungal infection include:-
- The primary barriers of defense, such as the skin and mucosa, are anatomically more fragile in children and more easily colonized.
- Neonates generally have functionally immature phagocytes and T lymphocytes witch make the immune system week and easily invaded with fungi.
- Prematurity, as gestational age and low birth weight clearly are associated with risk for invasive fungal infection.
- The frequent use of broad-spectrum antibiotics especially when administered for more than a week, has been associated with elimination of protective bacterial flora, and give chance for opportunistic fungal infection.
- Antancids, such as H-2 blockers and proton pump inhibitors, and corticosteriods are also thought to increase risk of candidiasis.
- The use of devices such as catheters and endotracheal tubes destroys the natural barriers of the body and allows fungi to penetrate, multiply and invade sterile body areas.
- Delayed enteral feeding and prolonged total parenteral nutrition, also are important risk factors for fungal infection in NICU.
- On the other hand, the longer NICU stay the more exposure to the therapeutic intervention and exposure to nosocomial infection, consequently we suggest that most of fungal infection in NICU are hospital acquired.
Diagnosis of fungal infections in neonates has been difficult because of insufficient sensitivity and specificity of conventional culture methods, and also by procedures that depend on the host functioning immune system, but within recent years, novel serological and molecular methods have been developed to improve the early diagnosis of invasive fungal infections which is essential for adequate therapeutic management.
Antifungal prophylaxis is currently applied in different NICUs and in various patients groups with successful results. Prophylactic drugs can include oral nystatin and oral or intravenous fluconazole. To date, antifungal prophylaxis with fluconazole is the recommended approach for neonates mainly in NICUs with relatively high frequency of invasive candidiasis.
Amphotericin B deoxycholate, fluconazole, or micafungin represent the treatment of choice in infants with IFIs. However, optimal dosage and duration of antifungal agents have not been fully tested in neonates, mainly in preterm infants, and their use still represent a challenge for neonatologists.
The aim of our study is to establish the correlation between the different risk factors and the incidence of fungal infection in neonates admitted to neonatal intensive care unit in Menoufia University Hospital.
Our study was conducted on 100 neonates: 50 cases, high risk neonates with one or more risk factors predisposing to fungal infection, after 5 days from admission to NICU. They were compared to control group of 50 healthy neonates after 5 days from admission to NICU.
Each neonate was subjected to:
1. History taking: Which included (pre-natal, natal, and post-natal).
2. Clinical examination: Which included (General examination, Local examination).
3. Laboratory investigations: Which included:-
- Routine investigation as (CBC, Blood culture, liver and kidney function tests, CRP and serum electrolytes).
- Culture of blood samples and other swabs on special media for fungal growth and detection of susceptibility of isolates to antifungal drugs.
Our study revealed that the incidence of fungal infection in the NICU was 24% of the cases (16% candida and 8% aspergillus) which is a very high rate in comparing to the other studies.
We found that the major risk factor for fungal infection in our NICU was the long stay in NICU with mean (8.34±5.06) (p˂0.001) value which is associated with the other risk factors which were respectively, prolonged use of antibiotics, prolonged TPN, use of devices, and delayed enteral feeding.
Prematurity ˂ 32 weeks and low birth weight, which are known to be the most important risks for fungal infection, came in our study second to the long stay in NICU as in our study prematurity was in (16%) of but it also resemble a significant risk for fungal infection ( p value= 0.006).
Use of devices carried a high significant risk for fungal infection especially use of endotracheal tubes ETT (mechanical ventilation) as it used in (68%) of cases, followed by central venous catheters (CVC) (48%) and umbilical venous catheters (UVC) (44%). (P value˂0.001) for each.
The use of prolonged antibiotics was a risk factor of high significance especially the combination of two or three antibiotics as, it resembles (96% Vs 78%, 76% Vs 0%, 58% Vs 0%, 48% Vs 0%, 18% Vs 0%) for (Ampicillin/sulbactam) + Amikacin, ceftazidime, Vancocin + (Imipenem/Cilastatin), metronidazole and Others (Cipro. , Piperacillin/ Tazobactam , Teicoplanin) respectively. Also the use of H2 blocker, was a significant risk factor in (26%) of cases only.
Also prolonged TPN (82%), and delayed enteral feeding (56%) were very important risk factors for developing of fungal infection in NICU (p value˂0.001)
Our study reported significant increase in CRP level in cases (2-96 gm. /L) as compared to control group (2-12 gm/L) (p value < 0.001).
Also there was significant difference of level of CRP between survived and died groups, as mean CRP was (45.03±36.47) for died cases and (16.0±21.59) for improved cases.
Our study reported that there was highly significant difference between cases and controls regarding to Fungal colonization of oral mucous membrane by candida species being occurred in (34%) of cases only, not in controls (p value < 0.001). as colonization considered a risk factor for fungemia.
Fungal blood cultures were +ve for fungal growth in 12 cases (24%) which were 8 with candidal growth and 4 with aspergillus growth.
Our study showed that there was significant association between +ve fungal blood cultures and high level of both clinical sepsis score and hematological sepsis score among cases (p value < 0.05).
Our study observed that there was no significant difference between cases with +ve or –ve fungal blood culture as regard to fungal colonization of oral mucous membrane, which occurred in (66.7%) of cases with +ve fungal blood culture and in (65%) of cases with –ve fungal blood culture. (And this may be due to that 78% of cases were receiving fluconazole as antifungal prophylaxis).
Our study reported that 43 devices (31.1%) of all devices used in cases were +ve for fungal growth when cultured on Sabouraud dextrose agar. As follow 13/34 (38%) endotracheal tubes, 6/24 (25%) central venous catheters, 3/22 (13.6%) umbilical venous catheters, 16/39 (41%) Ryle, 2/13 (15.4) chest tube and 3/6 (50%) other devices with total 22 (44%) cases with at least one culture positive device.
Regarding the correlation between + ve fungal cultures for both blood and devices in our study, there was significant use of devices among the cases with +ve fungal blood culture, as (100%) for use of both ETTs and Ryle, (75%) for CVCs, (50%) for UVCs, (25%) for chest tubes and ( 16%) for other devices (urinary catheter, Drain ..).
Also our study revealed that positive culture in endotracheal tube, central venous catheter and Ryle were significantly associated with positive fungal blood culture (p value <0.05). As in the cases with +ve fungal blood culture; it was found that the used devices for them were significantly had +ve fungal cultures with a percent more than the used devices for the cases with –ve fungal blood cultures, it represents (66.7% Vs 22.7%, 66.7% Vs 29.6%, 66.7% Vs 0%, 55.6% Vs 6.7%, 16.7% Vs 12.5%) for their (ETTs, Ryles, chest tubes, CVCs and UVCs) respectively. But regarding to chest tubes, UVCs and other devices (urinary catheter, Drain ...), there was a small sample size so there was no statistically significant association between their +ve culture and +ve blood culture.
The susceptibility of isolates to antifungal drugs were:-
For blood cultures: - Amphotricin-B (91.7%) followed by caspofungin (75%), both fluconazole and flucytocin were (25%) and Ketoconazole (8.3%).
For devices cultures:- Among total 43 culture positive devices, there was 23.3% ketoconazole sensitive, 37.2% fluconazole sensitive, 65.1% amphotricin B sensitive, 44.2% flucytocin sensitive and 55.8% caspofungin sensitive.
The outcome of the cases group show that 20 neonate survived (40%), 2 neonates were referred (4%) while 28 neonate were died (56%) while the control group were completely survived (P value < 0.001).
Through our study there were 5 patients stayed more than 20 days in NICU, so we secondly evaluate them with another fungal blood culture and we found that there was a significant association between prolonged stay in NICU more than 20 days and incidence of fungal infection which was +ve in 4 of them (80%) after staying in NICU more than 20 days (p value < 0.05).