Fungal Infection In Preterm Neonates Research Articles

Fungal cutaneous microbiome and host determinants in preterm and term neonates.

The neonatal cutaneous mycobiome has not been characterized in preterm infants. Invasive fungal infections in preterm neonates are associated with high mortality. The immaturity of the preterm skin predisposes neonates to invasive infection by skin colonizers. We report the clinical and host determinants that influence the skin mycobiome. Skin swabs from the antecubital fossa, forehead, and gluteal region of 15 preterm and 15 term neonates were obtained during the first 5 weeks of life. The mycobiome was sequenced using the conserved pan-fungal ITS2 region. Blood samples were used to genotype immune modulating genes. Clinical metadata was collected to determine the clinical predictors of the abundance and diversity of the skin mycobiome. The neonatal mycobiome is characterized by few taxa. Alpha diversity of the mycobiome is influenced by antibiotic exposure, the forehead body site, and the neonatal intensive care unit (NICU) environment. Beta diversity varies with mode of delivery, diet, and body site. The host determinants of the cutaneous microbiome include single-nucleotide polymorphisms in TLR4, NLRP3,CARD8, and NOD2. The neonatal cutaneous mycobiome is composed of few genera and is influenced by clinical factors and host genetics, the understanding of which will inform preventive strategies against invasive fungal infections.

Effect of Enteral Lactoferrin Administration on Invasive Fungal Infections in Preterm Neonates

Effect of Enteral Lactoferrin Administration on Invasive Fungal Infections in Preterm Neonates

Duration and intensity of fluconazole for prophylaxis in preterm neonates: a meta-analysis of randomized controlled trials.

BackgroundThe currently available evidence shows fluconazole is an effective prophylaxis treatment against invasive fungal infections in preterm neonates in neonatal intensive care units (NICUs). However, the duration and dosing of this prophylaxis treatment remain controversial. Thus, a meta-analysis and systematic review are necessary.MethodsPubMed and EMBASE were systematically searched with no restrictions. All relevant citations that compared prophylactic fluconazole and no prophylaxis were considered for inclusion. Pooled effect estimates were obtained through fixed- and random-effects meta-analyses, and a meta-regression was used to explore the sources of heterogeneity in the data.ResultsFive independent randomized controlled clinical trials (RCTs) involving 1006 preterm neonates were identified. Compared with no prophylaxis, the overall combined relative risks (RRs) of invasive fungal infection with the 28- and 42-day durations of prophylactic fluconazole were 0.80 (95 % CI 0.48–1.35, p = 0.4048) and 0.30 (95 % CI 0.15–0.58, p = 0.0004), respectively. The fluconazole dose had no significant impact on the RR of invasive fungal infections. The RR of mortality presented no significant differences between prophylactic fluconazole and no prophylaxis (RR 0.82, 95 % CI 0.60 to 1.12, p = 0.2093).ConclusionsProphylaxis with fluconazole for 42 days was found to be superior to no prophylaxis as a strategy for preventing invasive fungal infection in preterm infants in NICUs except in terms of mortality. The dosing regimen of prophylactic fluconazole may have no impact on the outcome; however, due to the limitations of the available data, further research is needed.

Probiotic supplementation for preventing invasive fungal infections in preterm neonates--a systematic review and meta-analysis.

Invasive fungal infections (IFI) are associated with significant health burden in preterm neonates. The objective of this study was to systematically review effect of probiotic supplementation (PS) for preventing IFI in preterm neonates. We searched Cochrane Central Register of Controlled Trials, Medline, Embase, Cumulative Index of Nursing and Allied Health Literature, and proceedings of the Pediatric Academic Society meetings in August 2014. Study selection was performed on randomised controlled trials (RCT) of PS in neonates born <37 weeks. Primary outcome of this study was IFI (Isolation of fungus in blood/body fluids) and secondary outcome was fungal gut colonisation. Information on IFI/colonisation was available in 8 of 27 RCT. Meta-analysis (fixed effects model) showed that PS reduced the risk of IFI (RR: 0.50, 95% CI: 0.34, 0.73, I(2) = 39%). Results were not significant with random effects model (RR: 0.64, 95%, CI: 0.30, 1.38, P = 0.25, I(2) = 39%). Analysis after excluding the study with a high baseline incidence (75%) of IFI showed that PS had no significant benefits (RR: 0.89; 95% CI: 0.44, 1.78). Of the five studies reporting on fungal gut colonisation, three reported benefits of probiotics; two did not. Current evidence is limited to derive firm conclusions on the effect of PS for preventing IFI/gut colonisation in preterm neonates.

Update on the management of Candida infections in preterm neonates

Invasive fungal infections in preterm neonates in the neonatal intensive care unit are predominantly caused by Candida spp, and have a high burden of morbidity and mortality. Effective prophylactic strategies...

Mannose-binding lectin codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit

Objective. Preterm neonates are susceptible to infection due to a combination of sub-optimal immunity and increased exposure to invasive organisms. Invasive fungal infections are associated with significant morbidity and mortality among preterm infants cared for in the neonatal intensive care unit (NICU). Mannose-binding lectin (MBL) is a component of the innate immune system, which may be especially important in the neonatal setting. The objective of this study was to investigate the presence of any association between MBL gene polymorphism and nosocomial invasive fungal infection in preterm neonates.Methods. Codon 54 (B allele) polymorphism in exon 1 of the MBL gene was investigated in 31 patients diagnosed as nosocomial invasive fungal infection and 30 control preterm neonates.Results. AB genotype was determined in 26% and 30% of patient and control groups, respectively, and the difference was not statistically significant. AA genotype was determined in 74% of the patient group and in 67% of the control group, and the difference was not statistically significant. B allele frequency was not different significantly in the patient group (13%) compared to the control group (18%).Conclusions. In our study, no relationship was found between MBL codon 54 gene polymorphism and the risk of nosocomial invasive fungal infection in preterm neonates in NICU.

AO-27. Mannose-binding lectin (MBL) codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit

AO-27. Mannose-binding lectin (MBL) codon 54 gene polymorphism in relation to risk of nosocomial invasive fungal infection in preterm neonates in the neonatal intensive care unit

Type and number of sites colonized by fungi and risk of progression to invasive fungal infection in preterm neonates in neonatal intensive care unit

Retrospective cohort study to assess if different patterns of Candida colonization determine different risks of progression to invasive fungal infection (IFI) in preterm neonates in NICU. Weekly surveillance cultures from all neonates weighing at birth <1500 g admitted over a 6-year period were reviewed. Infants with available results from at least 3 cultures/week and from at least 4 different sites were enrolled and identified by the number of sites involved [1-2 (low-grade), 3 or more (high-grade)] and type (low-risk, if colonization was recovered from skin, stool, ear canal swab, gastric aspirate, nasopharynx secretions, endotracheal tube; high-risk, from urine, catheter tip, drains, surgical devices). Progression rates from colonization to IFI were calculated for each subgroup. Univariate analysis was performed looking for significant associations between IFI and a number of risk factors, including the different subgroups of colonization. Multiple logistic regression assessed all significantly (P<0.05) associated risk factors. In the 405 eligible infants, overall colonization rate was 42.9%, IFI rate 9.9%, overall progression rate to IFI 0.23, the latter being significantly higher in high-grade or high-risk than in low-grade or low-risk colonized infants (0.59 vs. 0.18, P=0.001; 0.44 vs. 0.11, P<0.001, respectively). Infants with concomitant high-grade + high-risk colonization had 4-fold higher risk of progression than any other colonized infant, and 7-fold higher risk than infants concomitantly low-grade + low-risk colonized (P<0.001). At multivariate analysis, high-grade and high-risk colonization (P=0.001 for both), birth weight (P=0.02) and presence of central venous line (P=0.04) remained independent predictors of IFI. Density and severity of fungal colonization condition the progression to IFI in preterm infants in NICU, and certain patterns of colonization are independent predictors of IFI. Increased culture surveillance and prophylactic measures should be addressed to preterm colonized infants in NICU featuring the most risky colonization patterns.

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

Infections fongiques invasives du grand prématuré

Fungal infections were frequent in premature baby (<1500 g) and were associated with significant morbidity and mortality. In this paper we review the risk factors for invasive fungal infections and clinical settings. A better understanding of the mechanism of fungal infection in preterm infants is important in treatment and prevention. The early neonatal intensive care unit course favours colonization and proliferation of fungi since many preterm infants have central catheters and are exposed to broad spectrum antibiotics and parenteral nutrition. The majority of fungal infections in preterm neonates are due to Candida, with a small number due to other yeasts such as Malassezia. Candida is an opportunistic pathogen, which adheres to the skin, mucosal, and catheter surface. C. albicans account for 50% of cases of fungal sepsis. C. parapsilosis is the second most prevalent species in very low birth weight children; its frequency increased from 1995 to 2000. Risk factors for fungal colonization are: very low birth weight, exposure to broad spectrum antibiotics, parenteral nutrition and use of corticosteroids. Colonization of the skin, gastro-intestinal tract and respiratory tract and central vascular catheter precede infection. The majority of preterm infants with fungal infections develop thrombocytopenia, but this is a common feature shared with other sepsis. The evaluation of infants with fungal sepsis should include cerebrospinal fluid examination and culture of urine with surveillance for endocarditis, renal, liver and brain abscesses and endophthalmitis. The mortality rate can reach 30%, and is higher in very low birth weight infants.

Risk Factors for Progression to Invasive Fungal Infection in Preterm Neonates With Fungal Colonization

Colonization by Candida spp is a major risk factor for development of fungal sepsis, but little is known about the variables associated with progression to invasive disease in already colonized neonates. We investigated such variables in a large number of colonized preterm neonates in an NICU. This study was conducted in the Department of Neonatology and the NICU at Sant'Anna Hospital in Torino, Italy. A database search of clinical charts and weekly surveillance cultures was used to identify all neonates with birth weights < 1500 g (very low birth weight) who were admitted to our NICU during 1998-2005 and were colonized (> or = 1 site) by Candida spp during their stay, as well as infants with invasive fungal infection. The association between a number of factors with progression to invasive fungal infection was evaluated. Those shown to be significantly associated by univariate analysis were cross-checked by logistic regression. Colonization occurred in 201 infants (32.1% of very low birth weight admitted neonates), and invasive fungal infection occurred in 51 (8.1%) of them, with an overall progression rate of 0.25. At univariate analysis, 10 factors (namely low birth weight, low gestational age, use of third-generation cephalosporins, endotracheal intubation, duration of stay in the NICU, bacterial sepsis, colonization of central venous catheter, of endotracheal tube, of gastric aspirate, or in > or = 3 [multiple] sites) were associated with an increased risk of progression, whereas prophylaxis with fluconazole was associated to a decreased risk. After logistic regression, only colonization of central venous catheter and colonization in multiple sites remained significantly associated with invasive fungal infection. Fluconazole prophylaxis remained an independent protective factor. Central venous catheter colonization and multiple-site colonization are independent risk factors and predictors of progression to fungal sepsis in preterm very low birth weight neonates colonized by Candida spp during their stay in the NICU. Fluconazole prophylaxis is an independent protective factor. These findings can be used to improve the surveillance, prophylaxis, or preemptive measures in neonates at high risk.

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

Abstract Aim: The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. Methods: We performed a case‐control study on neonates with birthweight less than 1250 g admitted to our tertiary‐level unit during the years 1998–2004 (n=383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late‐onset sepsis caused by bacterial agents (n=46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia &gt; 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Results: Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235–4.432, p=0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p=0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Conclusions: Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late‐onset sepsis, with a typical 3‐d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.

Hyperglycaemia as a possible marker of invasive fungal infection in preterm neonates

The incidence of invasive fungal infection in preterm newborns is rising steadily. Early recognition and treatment are imperative, but diagnosis is difficult as data from microbiological investigations are often poor, and clinical and laboratory signs do not help in differentiating bacterial from fungal infections. We evaluated whether glucose intolerance could represent a possible surrogate marker predictor of invasive fungal infection in preterm neonates. We performed a case-control study on neonates with birthweight less than 1250 g admitted to our tertiary-level unit during the years 1998-2004 (n = 383), comparing those with invasive fungal infection (n = 45, group A) to matched controls with late-onset sepsis caused by bacterial agents (n = 46, group B). We investigated in both groups the occurrence of hyperglycaemia (serum glycaemia > 215 mg/dl, i.e. 12 mmol/l) in the first month of life, and its temporal relationship with the episodes of sepsis. Hyperglycaemia occurred significantly more often in group A (21/45, 46.6%) than in group B neonates (11/46, 23.9%) (OR 1.95, 95% CI 1.235-4.432, p = 0.008). Moreover, in 19 of 21 (90.4%) neonates with hyperglycaemia in group A, the carbohydrate intolerance episode typically occurred 72 h prior to the onset of invasive fungal infection; in contrast, no temporal relationship was found in neonates with bacterial sepsis (p = 0.002). Correction of hyperglycaemia was successfully achieved in all neonates of both groups, with no significant differences in the number of days of insulin treatment needed to normalize glycaemia (p = 0.15). Hyperglycaemia is significantly more frequent in neonates who subsequently develop fungal rather than bacterial late-onset sepsis, with a typical 3-d interval. We suggest that a preterm neonate whose birthweight is less than 1250 g in its first month of life should be carefully evaluated for systemic fungal infection whenever signs of carbohydrate intolerance occur.