Clinical characteristics and response to prophylactic fluconazole of preterm VLBW neonates with baseline and acquired fungal colonisation in NICU: data from a multicentre RCT.

BACKGROUND: Fungal colonisation by Candida spp. affects a high proportion of VLBW neonates in NICU. However, few data are available on the clinical characteristics of colonisation in preterm infants who are colonised at baseline via vertical transmission, compared to preterms who become colonised during their stay in NICU via horizontal transmission. MATERIAL AND METHODS: We reviewed the database of a multicentre, randomised trial of prophylactic fluconazole in VLBW neonates conducted in 8 Italian NICUs in the years 2004 and 2005 (Manzoni et al., NEJM 2007;356(24):2483-95). Per the protocol, all enrolled infants underwent weekly surveillance cultures from birth till discharge. We investigated the frequency of the two different modalities of Candida colonisation in this population, as well as the clinical and outcome characteristics possibly related to them. RESULTS: Overall, Candida colonisation affected 54 of 336 infants (16.1%). Baseline (i.e., detected <3(rd) day of life) colonisation affected 16 (4.7%), and acquired 38 (11.4%), of the 54 colonised preterms. Infants with baseline colonisation had significantly higher birth weight (1229 ± 28 g vs. 1047 g ± 29, p = 0.01) and gestational age (30.2 wks ± 2.7 vs. 28.5 wks ± 2.6, p = 0.01), and were significantly more likely to limit progression from colonisation to invasive Candida infection when fluconazole prophylaxis was instituted (21.6% vs. 42.7%, p = 0.009). Isolation of C. parapsilosis was significantly more frequent in infants with acquired colonisation. CONCLUSIONS: Infants with baseline and acquired colonisation differ for demographics characteristics and for their response to fluconazole prophylaxis. This information may be useful for targeting more accurate management strategies for these two different groups of colonised preterms in NICU.

Recent advances in prevention of sepsis in the premature neonates in NICU.

Sepsis-related morbidity and mortality are major problems in NICU. Preterm neonates display clinical characteristics that make them prone to infections. Due to the high frequency of severe neurodevelopmental sequelae in survivors, the best possible strategy to manage sepsis in NICU is to prevent them. Hygiene, cohorting, stewardship on use of H2-blockers, steroids and broad-spectrum antibiotic are mandatory, as well as proper management of central venous accesses and surgical devices. In addition, clinical research offers the opportunity of adopting pharmacological preventative strategies such as use of palivizumab to prevent RSV infection, use of fluconazole to prevent fungal sepsis, use of probiotics and lactoferrin to enhance the innate immunity, and use of pagibaximab to prevent staphylococcal sepsis.

Lactoferrin and prevention of late-onset sepsis in the pre-term neonates.

Late-onset sepsis (LOS) affects a large proportion of pre-term neonates in neonatal intensive care units (NICUs) worldwide, with high morbidity and related mortality, and frequent occurrence of severe late neurodevelopmental impairment. Due to the frequency, severity and difficulties in early diagnosis and prompt therapy, prevention is crucial for decreasing the burden of infection-related complications in NICUs. It is well known that feeding with fresh maternal milk, hygiene measures and the cautious use of H2-blockers are related with a decreased risk of developing sepsis. However, evidence from randomised clinical trials exists only for fluconazole in the prevention of fungal infections in the NICU. Lactoferrin is the main whey protein in mammalian milk, and is involved in innate immune host defences. Notably, human lactoferrin can be found at increased concentrations in colostrum and in milk from mothers of premature neonates. Human (hLF) and bovine lactoferrin (bLF) share a high (77%) amino-acid homology, and the same N-terminal peptide responsible for antimicrobial activity, called lactoferricin. In vitro, bLF shows potent direct antimicrobial activity against all types of pathogens, which occurs via anti-cell wall actions and leads to disintegration of the micro-organism's membranes. bLF is also synergistic with many antimicrobials and antifungals, and promotes growth and differentiation of the immature gut. Based on this background data, a randomised clinical trial was recently conducted in very low birth weight pre-term neonates given bLF alone or with the probiotic Lactobacillus GG. The aim of the trial was to assess the ability of bLF to prevent late-onset sepsis of any origin in the studied infants during their stay in the NICU. This article discusses the preliminary data from this study, along with the proposed mechanisms of action of bLF in pre-term infants.

Nosocomial necrotising enterocolitis outbreaks: epidemiology and control measures.

UNLABELLED: Necrotising enterocolitis (NEC) is one of the most serious gastrointestinal diseases among newborns and it mainly affects those in intensive care units. The aetiology of the disease has been reported to be multifactorial and both sporadic cases and nosocomial outbreaks have occurred. In this report, we review 17 epidemics of NEC reported in the literature between 1973 and 1999. The number of confirmed cases ranged from 1 to 32 with an average of 10.5 confirmed cases. On average, 16.15% of cases required surgery (range 0-66.6%). The average mortality rate was 6.25% (range 0-87.5%). The mean age at disease onset was 9.5 days (range 6.6-29 days). Most of the infants had low birth weight (median weight 1,395 g; range 1,112-2,788 g, calculated on the reported mean weights). The main risk factors associated with NEC were: low birth weight, low gestational age, low Apgar score, perinatal complications, hyaline membrane disease, and umbilical catheterisation. The bacteria involved often included Enterobacteriaceae, particularly Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae type 3305573. The causative role of Clostridia in NEC is controversial. With regard to viral agents, coronarovirus, rotavirus and enterovirus, such as echovirus type 22, were isolated during some of the epidemics. The recommended control measures for NEC epidemics are those used for epidemics of other orofaecally transmitted infections. CONCLUSION: Understanding the epidemiology of necrotising enterocolitis is fundamental if adequate preventive control measures are to be developed and applied.

Risk factors for nosocomial sepsis in newborn intensive and intermediate care units.

UNLABELLED: A multicentre prospective study was performed to estimate the incidence of hospital infections and to identify the most relevant risk factors for sepsis in a large and unselected population of high-risk newborns. The study involved 49 neonatal intensive care units and 17 neonatal intermediate care units in Italy. Newborns were followed up from admittance to the units until discharge. Data on demographics and clinical characteristics, exposure to the principal invasive procedures, and onset of infectious complications were prospectively collected. Only infections developing after 48 h from admittance to the unit were recorded. A multiple logistic regression was performed to identify which factors were independently associated with sepsis. Among the 8263 newborns included in the analysis, the incidence of infected newborns was 14.4 per 100 newborns and 0.9/100 days of stay. The incidence of infections was 19.1/100 newborns and 1.2/100 days of stay. Sepsis represented 15.4% of all infections (incidence 2.9/100 newborns and 0.2/100 days of stay). The following factors were independently associated with sepsis: umbilical catheterization, both through the vein and the artery for more than 5 days; mechanical ventilation for more than 5 days; necrotizing enterocolitis; birth weight equal to or less than 2500 g; nasogastric tube; total parenteral nutrition; and transfer from other hospitals. Umbilical catheters accounted for the highest proportion of sepsis (62%), followed by arterial catheters (31%), nasopharyngeal cannulae (26%), tracheal cannulae (20%), and nasal cannulae (20%). The population attributable risk for the other procedures was less than 10%. CONCLUSION: This study demonstrates that in a large and unselected newborn population, several host factors and invasive procedures are independently associated with an increased risk of sepsis. After adjustment for clinical severity, intravascular catheterization and assisted ventilation were found to be responsible for a considerable proportion of observed sepsis. They should therefore be considered as priorities for interventions, aimed both at reducing unnecessary use and promoting more strict compliance with aseptic practices.