Sepsis in early infancy results in one million annual deaths worldwide, most of them in developing countries. No efficient means of prevention is currently available. Here we report on a randomized, double-blind, placebo-controlled trial of an oral synbiotic preparation (Lactobacillus plantarum plus fructooligosaccharide) in rural Indian newborns. We enrolled 4,556 infants that were at least 2,000 g at birth, at least 35 weeks of gestation, and with no signs of sepsis or other morbidity, and monitored them for 60 days. We show a significant reduction in the primary outcome (combination of sepsis and death) in the treatment arm (risk ratio 0.60, 95% confidence interval 0.48-0.74), with few deaths (4 placebo, 6 synbiotic). Significant reductions were also observed for culture-positive and culture-negative sepsis and lower respiratory tract infections. These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic containing L. plantarum ATCC-202195.

A randomized synbiotic trial to prevent sepsis among infants in rural India

Heart Disease : A Textbook of Cardiovascular Medicine, 5th Ed.

Background Invasive fungal infection is an important cause of mortality and morbidity in very low birth weight infants. Early diagnosis is difficult, and treatment is often delayed. The available data are insufficient to conclude that topical/oral prophylaxis (usually nystatin and/or miconazole) prevents invasive fungal infection or mortality in very low birth weight infants. Systemic antifungal agents (usually azoles) are increasingly used as prophylaxis against invasive fungal infection. Objectives To assess the effect of prophylactic systemic antifungal therapy on mortality and morbidity in very low birth weight infants. Search strategy The standard search strategy of the Cochrane Neonatal Review Group was used. This included searches of the Cochrane Controlled Trials Register (The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - May 2007), EMBASE (1980 - May 2007), conference proceedings, and previous reviews. Selection criteria Randomised controlled trials that compared the effect of prophylactic systemic antifungal therapy versus placebo, or no drug, or another antifungal agent or dose regimen, in very low birth weight infants. Data collection and analysis Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by each author, and synthesis of data using relative risk, risk difference, and weighted mean difference. The pre-specified outcomes were death prior to hospital discharge, long-term neurodevelopment, incidence of invasive fungal infection, emergence of antifungal resistance, and adverse drug reactions. Main results Seven eligible trials enrolling a total of 638 participating infants were identified. Meta-analysis of data from four trials that compared prophylactic fluconazole versus placebo revealed a statistically significant reduction in the risk of invasive fungal infection in the infants who received prophylaxis [typical relative risk: 0.23 (95% confidence interval 0.11, 0.46); typical risk difference: -0.11 (95% confidence interval -0.16, -0.06); number needed to treat: 9 (95% confidence interval 6, 17)]. There was no statistically significant difference in the risk of death prior to hospital discharge [typical relative risk: 0.61 (95% confidence interval 0.37, 1.03); typical risk difference: -0.05 (95% confidence interval -0.11, -0.00)]. Only one trial reported long term neurodevelopmental outcomes. There were no statistically significant differences in the incidence of developmental delay, or motor or sensory neurological impairment in children assessed at a median age of 16 months. One small trial that compared systemic versus oral/topical prophylaxis did not detect a statistically significant effect on invasive fungal infection or mortality. Two trials compared different dosing regimens of prophylactic intravenous fluconazole. These did not detect any significant differences in infection rates or mortality. Authors' conclusions Prophylactic systemic antifungal therapy reduces the incidence of invasive fungal infection in very low birth weight infants. This finding should be interpreted cautiously. The incidence of invasive fungal infection was very high in the control groups of some of the included trials. Furthermore, the trials may have been affected by ascertainment bias since use of prophylactic fluconazole may reduce the sensitivity of microbiological culture for detecting fungi in blood, urine, or cerebrospinal fluid. Meta-analysis does not demonstrate a statistically significant effect on overall mortality rates, but the 95% confidence interval around this estimate of effect is wide. There are currently only limited data on the long-term neurodevelopmental consequences for infants exposed to this intervention. In addition, there is a need for further data on the effect of the intervention on the emergence of organisms with antifungal resistance.

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Prophylactic systemic antifungal agents to prevent mortality and morbidity in very low birth weight infants

Brucellosis, caused by bacteria of the genus Brucella, is an important zoonotic infection that causes reproductive disease in domestic animals and chronic debilitating disease in humans. An intriguing aspect of Brucella infection is the ability of these bacteria to evade the host immune response, leading to pathogen persistence. Conversely, in the reproductive tract of infected animals, this stealthy pathogen is able to cause an acute severe inflammatory response. In this review, we discuss the different mechanisms used by Brucella to cause disease, with emphasis on its virulence factors and the dichotomy between chronic persistence and reproductive disease.

Brucella spp. Virulence Factors and Immunity

Neonatal hypoxic ischemic encephalopathy-related biomarkers in serum and cerebrospinal fluid.

OBJECTIVES: The goal was to investigate the effect of orally administered synbiotics on outcome of infants with cyanotic congenital heart disease (CCHD). METHODS: A prospective, blinded, randomized controlled trial was conducted to evaluate the effect of synbiotics on outcome of infants with CCHD. The infants with CCHD were assigned randomly to 2 groups. Infants in the study group were given synbiotic ( Bifidobacterium lactis plus inulin) added to breast milk or mixed feeding until discharge or death. Infants in the placebo group were fed with breast milk or mixed feeding. The outcome measurements were nosocomial sepsis, necrotizing enterocolitis (NEC; Bell stage ≥2), length of NICU stay, and death. RESULTS: A total of 100 infants were enrolled in the trial: 50 in each arm. There were 9 cases of culture-proven sepsis (18%) in the placebo group and 2 cases (4%) in the synbiotic group ( P = .03). Length of NICU stay did not differ between the groups (26 [14–36] vs 32 days [20–44], P = .07]. There were 5 cases of NEC (10%) in the placebo group and none in the synbiotic group ( P = .03). The incidence of death was lower in synbiotic group (5 [10%] of 50 vs 14 [28.0%] of 50, respectively; P = .04). CONCLUSIONS: Synbiotics administered enterally to infants with CCHD might reduce the incidence of nosocomial sepsis, NEC, and death.

Treatment Outcomes of Infants With Cyanotic Congenital Heart Disease Treated With Synbiotics

To determine the role of mean platelet volume (MPV) and uric acid levels in the diagnosis of neonatal sepsis (NS). A total of 146 newborns with suspected NS were prospectively included in the study and infants without NS (n = 142) were assigned as controls. The patients were divided into three groups: Group I (n = 64): clinical NS, Group II (n = 82): culture-proven NS, and Group III (n = 142): healthy controls. The patients in Group II had the highest C-reactive protein (CRP) levels (54.6 ± 5.4 mg/L), lowest platelet counts (199,329 ± 135,952/mm3) and lowest uric acid levels (2.6 ± 1.8 mg/dL) when compared to Groups I and III (p < 0.05, for all comparisons). MPV values were higher in Group I (10.6 ± 1.1 fL) and Group II (10.4 ± 0.9 fL) when compared to Group III (9.2 ± 1.2 fL) (p = 0.001), although there was no difference between Groups I and II. Area under curve (AUC) values for CRP, MPV, and uric acid were 0.92 (p = 0.001), 0.76 (p = 0.001) and 0.28 (p = 0.001), respectively. The diagnostic cut-off values for CRP and MPV were 9.5 mg/dL and 10.4 fL. Sensitivity and specificity of MPV in NS were 54 % and 82 % respectively. When combined with CRP its sensitivity and specificity increased to 89 % and 79 % respectively. The combined use of CRP and MPV should be considered in the early diagnosis of NS, but uric acid levels may only be utilized as an additional tool to support diagnosis. CRP is shown to be more sensitive and specific than MPV and uric acid in diagnosing neonatal sepsis.

Mean platelet volume and uric acid levels in neonatal sepsis.

Hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia remains an important cause of neonatal morbidity and mortality. The aim of this study was to investigate the predictive values of biochemical parameters, including serum creatine kinase (CK), lactate dehydrogenase (LDH), uric acid (UA), and lactate, in newborns with HIE. A total of 94 patients who were diagnosed with HIE were prospectively enrolled into the study. According to the Sarnat and Sarnat classification, 29 (30.9%) patients had Stage I, 36 (38.3%) Stage II, and 29 (30.9%) Stage III HIE. When CK, LDH, UA, and lactate were used together in order to determine the stage of HIE, specificity and sensitivity were calculated to be 87% and 94%, respectively. Measurement of serum CK, LDH, lactate, and UA levels together is a promising method in determining the stage of hypoxia in the laboratory before clinical manifestations occur so that hypothermia treatment can be initiated earlier.

Can biochemical markers predict the severity of hypoxic- ischemic encephalopathy?

Brucellosis is a zoonosis caused by ingestion of unpasteurized milk or other dairy products from infected animals or through close contact with their secretions. Human-to-human transmission, which is rare, has been reported in association with blood transfusion, bone marrow transplantation, transplacental or perinatal exposure, and breastfeeding. In the neonatal period, congenital brucellosis, which is an extremely rare condition, can lead to serious clinical consequences with a high morbidity and mortality rate. The case presented here is a premature baby born at 25 weeks’ gestation to a mother suffering from severe oligohydramnios, premature rupture of membranes and untreated acute brucellosis. The baby had severe respiratory distress and radiological findings compatible with pulmonary infection. The blood cultures of the baby and the mother were positive for Brucella melitensis, supporting the diagnosis of brucellosis with presumed transplacental transmission. Brucellosis is a zoonotic disease with a worldwide distribution. It is transmitted from animals to humans through unpasteurized milk and other improperly cooked dairy products; meat and meat products from infected animals; direct contact with the contaminated area; and the inhalation of contaminated animal feces, which dry off and become dust-like 1 . Human-tohuman transmission is rare. Only 20 neonatal cases with congenital brucellosis caused by transplacental exposure have been reported in the literature thus far 2 . The majority of these cases exhibited non-specific symptoms and findings. Here, we report a case of congenital brucellosis with presumed transplacental transmission in a premature newborn suffering from severe pulmonary involvement in the course of the disease.

Prematurity due to maternal brucella infection and review of the literature

Cupriavidus pauculus is a gram-negative, aerobic, non-spore forming, non-fermentative motile bacillus. The bacillus can be isolated from water, bottled mineral water, and water from ultrafiltration systems in hospital setting. C. pauculus rarely causes human infections, however it may be an infectious agent especially in immunocompromised individuals. In this report, we present the first case of community acquired pneumonia caused by C. pauculus in a previously healthy newborn who was hospitalized in neonatal intensive care unit on postnatal day 16 because of respiratory distress.

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Banu Aydin

Papers

Treatment Outcomes of Infants With Cyanotic Congenital Heart Disease Treated With Synbiotics

Mean platelet volume and uric acid levels in neonatal sepsis.

Can biochemical markers predict the severity of hypoxic- ischemic encephalopathy?

Prematurity due to maternal brucella infection and review of the literature

A case of newborn with community acquired pneumonia caused by Cupriavidus pauculus