Oral Nystatin Prophylaxis to Prevent Systemic Fungal Infection in Very Low Birth Weight Preterm Infants

Study Overview
=================
Brief Summary
-----------------
This study determines the effectiveness of oral nystatin as prophylaxis in order to prevent systemic fungal infection in very low birth weight preterm neonates. 47 participants received oral nystatin and 48 participants received sterile water as part of oral hygiene.

Detailed Description
-----------------
Oral nystatin is an effective and safe alternative fungal prophylaxis. Some previous studies (1 randomized controlled trial and 4 observational studies) showed that oral nystatin prophylaxis reduce fungal colonization and decrease risk of systemic fungal infection in very low birth weight infants. Nystatin is a non-absorbable antifungal agent with minimal side effects that works by binding on the major component of fungus cell membrane and causes death of the fungus. Its efficacy as fungal prophylaxis is comparable with Fluconazole but does not linked to drug-induced liver injury. To determine this effectivity, we recruit eligible neonates who are admitted in our neonatal intensive care unit and randomly assign them into 2 groups once noted written parental consent. One group is given nystatin via oral and/or orogastric tube and the other group only receives sterile water as part of oral hygiene. Weekly fungal surveillance cultures (oropharyngeal and rectal) are done to evaluate colonization. Further examinations (blood/cerebrospinal fluid/deep tissue/urine culture) are done once noted clinical signs of systemic fungal infections. Data analysis is conducted with intent-to treat approach. Significance testing is done by chi-square or fisher's exact test as needed.

Official Title
-----------------
Oral Nystatin Prophylaxis to Prevent Systemic Fungal Infection in Very Low Birth Weight Preterm Infants: a Randomized Controlled Trial

Conditions
-----------------
Fungal Infections Systemic

Intervention / Treatment
-----------------
* Drug: Nystatin Oral


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Gestational age <= 32 weeks and/or birth weight <=1500 grams 1 or more systemic fungal infection risk factors (antibiotic therapy, intravenous access, endotracheal tube, orogastric tube, urinary catheter, corticosteroid therapy, parenteral nutrition, theophylline therapy) Exclusion Criteria: Suspected of having necrotizing enterocolitis within 72 hours after birth, cyanotic congenital heart disease, chromosomal defects, or critical conditions whom were not expected to live more than 72 hours after birth

Ages Eligible for Study
-----------------
Maximum Age: 3 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participants is randomly allocated into 2 study groups (nystatin group and control group) during study period
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nystatin group<br>Nystatin oral 1 mL (0.5 mL coated in oral cavity and the rest was given through orogastric tube) three times a day | Drug: Nystatin Oral<br>* Nystatin oral suspension<br>* Other names: Mycostatin;|
| No Intervention: Control group<br>Sterile water 1 mL three times a day for oral hygiene | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fungal colonization | Weekly oropharyngeal and rectal fungal surveillance results are evaluated. Colonization is considered positive if yeast cells were found on either oral or rectal specimen | 1 to 6 weeks | 
| Systemic fungal infection | Culture of blood, cerebrospinal fluid, deep tissue, or urine is evaluated in participants with symptoms/signs of systemic infection. Proven systemic fungal infection is defined as a positive blood, cerebrospinal fluid, deep tissue, or urine culture (> 10.000 or more colony forming unit/mL from sterile bladder catheterization or suprapubic aspiration) | 1 to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality rates | Fungal and overall related mortality rates | 1 to 6 weeks | 
| Nystatin-related adverse drug reactions | Any side effects of nystatin as reported in references | 1 to 6 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Nystatin, Fungal colonization, Systemic fungal infections