Clinical microbiology of bacterial and fungal sepsis in very-low-birth-weight infants

Twenty percent of very-low-birth-weight (<1500 g) preterm infants experience a serious systemic infection, and despite advances in neonatal intensive care and antimicrobials, mortality is as much as threefold higher for these infants who develop sepsis than their counterparts without sepsis during their hospitalization. Outcomes may be improved by preventative strategies, earlier and accurate diagnosis, and adjunct therapies to combat infection and protect the vulnerable preterm infant during an infection. Earlier diagnosis on the basis of factors such as abnormal heart rate characteristics may offer the ability to initiate treatment prior to the onset of clinical symptoms. Molecular and adjunctive diagnostics may also aid in diagnosing invasive infection when clinical symptoms indicate infection but no organisms are isolated in culture. Due to the high morbidity and mortality, preventative and adjunctive therapies are needed. Prophylaxis has been effective in preventing early-onset group B streptococcal sepsis and late-onset Candida sepsis. Future research in prophylaxis using active and passive immunization strategies offers prevention without the risk of resistance to antimicrobials. Identification of the differences in neonatal intensive care units with low and high infection rates and implementation of infection control measures remain paramount in each neonatal intensive care unit caring for preterm infants.     

Economic evaluation of neonatal intensive care of very-low-birth-weight infants

We evaluated the economic aspects of neonatal intensive care of very-low-birth-weight infants, using outcomes and costs of care before and after the introduction of a regional neonatal-intensive-care program. Neonatal intensive care increased both survival rates and costs. For newborns weighing 1000 to 1499 g, the cost (in 1978 Canadian dollars) was $59,500 per additional survivor, $2,900 per life-year gained, and $3,200 per quality-adjusted life-year gained; intensive care resulted in a net economic gain when figures were undiscounted but a net economic loss when future costs, effects, and earnings were discounted at 5 per cent per annum. For infants weighing 500 to 999 g, the corresponding costs were $102,500 per additional survivor, $9,300 per life-year gained, and $22,400 per quality-adjusted life-year gained; intensive care resulted in a net economic loss. By every measure of economic evaluation, the impact of neonatal intensive care was more favorable among infants weighing 1000 to 1499 g than among those weighing 500 to 999 g. A judgment concerning the relative economic value of neonatal intensive care of very-low-birth-weight infants requires a comparison with other health programs.     

Acute shift in immune response to microbial activators in very-low-birth-weight infants.

Investigation of lymphocyte activation in vitro to microbial pathogens was undertaken in very-low-birth-weight infants during the first 2 weeks of life. Twenty-three infants with birth weights less than 1500 g were studied on day 1. Normal adults (n = 23) and cord blood from seven full-term infants were used as controls. Longitudinal studies were also carried out on seven of the 23 infants 2 weeks following delivery. Results indicated that lymphocyte responses of very-low-birth-weight infants on day 1 of life were significantly greater than those of both adult controls and full-term infants, particularly to Haemophilus influenzae, Staphylococcus epidermidis and Staphylococcal protein A. In contrast, response to the T cell mitogen phytohaemagglutinin (PHA) was significantly less in very-low-birth-weight infants than in adult controls and full-term infants. The seven very-low-birth-weight infants studied showed a down-regulation of immune response in the 2 weeks following birth, such that responses on day 14 were significantly less than those on day 1 for the same activators. This shift in immune response appears to have important implications for the immune development and host defence in the post-natal period.     

儿童肠系膜淋巴结炎的病原体分析

目的分析儿童肠系膜淋巴结炎的病原体,为该病的临床诊断和治疗提供实验室依据。方法对2010年1月至2012年12月期间．湖北省黄冈地区门诊和住院已经确诊为儿童肠系膜淋巴结炎的1225例标本进行免疫学检验和细菌培养。结果从1225例送检标本中检出病毒1097例,其中柯萨奇病毒976例,埃可病毒121例。细菌培养检出细菌118例,阳性率为9．6％;其中溶血性链球菌73例,占61．9％;金黄色葡萄球菌31例,占26．2％;其他14例,占11．9％。结论病毒感染和溶血性链球菌、金黄色葡萄球菌等是造成儿童肠系膜淋巴结炎的主要病原体。     

Genetic variant rs16944 in IL1B gene is a risk factor for early-onset sepsis susceptibility and outcome in preterm infants

Objective

Interleukin-1-B (IL1B) is a proinflammatory cytokine that plays an important role in sepsis. The aim of this study was to evaluate the relationships between IL1B-511G/A polymorphism and susceptibility and outcome of early-onset sepsis (EOS) in preterm infants.

Methods

DNA was extracted from the buccal swabs of 471 (285 with EOS and 186 control) preterm infants. Genotypes of rs16944 polymorphism were determined with real-time PCR method.

Results

We found statistically significant higher frequency of IL1B-511AA genotype in EOS group than in control group (p?=?0.012). Also, IL1B-511AA genotype is statistically significantly more frequent in patients with lethal EOS outcome (p?=?0.011).

Conclusion

Genotype IL1B-511AA was associated with susceptibility to EOS and it is a significant predictor of lethal outcome in preterm infants with EOS.

     

Breast milk causing neonatal sepsis and death

Breast milk can occasionally transmit serious viral and bacterial infections to preterm infants. We present three cases of late-onset neonatal sepsis, including one that resulted in death, occurring in preterm infants. The likely source of the microorganisms in all three cases was expressed breast milk.     

Unconventional pathogens causing spongiform encephalopathies absent in blood products

To determine whether unconventional pathogens causing subacute spongiform encephalopathy may be present in blood products, a newly developed hepatitis B vaccine and a widely used blood product were injected into mice and rats. As only a few aged mice in the test and the control groups showed spongiform encephalopathic change of a sparse or mild degree and which differed from that seen in rodents infected with Creutzfeldt-Jakob disease, the presence of unconventional pathogens in the tested inocula can be ruled out.     

Plasma erythropoietin activity in infants with sepsis

Translated fromByulleten' Pksperimental'noi Biologii i Meditsiny, Vol. 115, N ^o 5, pp. 499–502, May, 1993     

Congenital bacterial sepsis in very preterm infants.

The results of body fluid and surface cultures from 148 preterm infants less than 33 weeks gestational age obtained routinely on admission to a neonatal intensive care unit were reviewed. The aim was to determine the occurrence of congenital bacterial sepsis in this population and to examine whether surface cultures yielded information helpful in management. Gastric aspirate and umbilical, nasal and ear swabs were cultured and the results were compared to those of blood cultures. Nine infants (5.4%) had congenital bacterial sepsis diagnosed by positive blood cultures. Only the results of microscopy of gastric aspirate were available within hours of birth and before the results of blood culture. Microscopy of gastric aspirate, demonstrating pus cells, alone had a sensitivity of 0.86 in predicting congenital sepsis but a specificity of 0.49; the specificity, however, rose to 0.80 if both organisms and pus cells were observed on microscopy. Thus, only this combination was a useful pre-indicator of congenital sepsis. In infants who did not develop septicaemia, treatment was modified only if Streptococcus agalactiae was cultured from surface sites; in all such cases, the organism was grown from the ear swab. Our results demonstrate that congenital bacterial sepsis is common amongst very preterm infants admitted for neonatal intensive care but routine screening of surface cultures should be restricted to an ear swab only.     

Relationship between maternal serum C-reactive protein, funisitis and early-onset neonatal sepsis

The aim of this study was to determine whether maternal serum C-reactive protein (CRP) is of value in predicting funisitis and early-onset neonatal sepsis (EONS) in women with preterm labor or preterm premature rupture of membranes (PROM). This retrospective cohort study included 306 consecutive women with preterm labor or preterm PROM who delivered preterm singleton neonates (23-35 weeks gestation) within 72 hr of CRP measurement. The CRP level was measured with a highly sensitive immunoassay. The sensitivity, specificity, positive predictive value, and negative predictive value of an elevated serum CRP level (≥ 8 mg/L) were 74.1%, 67.5%, 32.8%, and 92.4% for funisitis, and 67.7%, 63.3%, 17.2%, and 94.6% for EONS, respectively. Logistic regression analysis demonstrated that elevated levels of serum CRP were significantly associated with funisitis and EONS, even after adjusting gestational age. The maternal serum CRP level obtained up to 72 hr before delivery is an independent predictor of funisitis and EONS in women with preterm labor or preterm PROM. A low serum CRP level (< 8 mg/L) has good negative predictive value in excluding funisitis and EONS, and may therefore be used as a non-invasive adjunct to clinical judgment to identify low-risk patients.     

A randomized clinical trial of early hospital discharge and home follow-up of very-low-birth-weight infants

To determine the safety, efficacy, and cost savings of early hospital discharge of very-low-birth-weight infants (less than or equal to 1500 g), we randomly assigned infants to one of two groups. Infants in the control group (n = 40) were discharged according to routine nursery criteria, which included a weight of about 2200 g. Those in the early-discharge group (n = 39) were discharged before they reached this weight if they met a standard set of conditions. For families of infants in the early-discharge group, instruction, counseling, home visits, and daily on-call availability of a hospital-based nurse specialist for 18 months were provided. Infants in the early-discharge group were discharged a mean of 11 days earlier, weighed 200 g less, and were two weeks younger at discharge than control infants. The mean hospital charge for the early-discharge group was 27 percent less than that for the control group ($47,520 vs. $64,940; P less than 0.01), and the mean physician's charge was 22 percent less ($5,933 vs. $7,649; P less than 0.01). The mean cost of the home follow-up care in the early-discharge group was $576, yielding a net saving of $18,560 for each infant. The two groups did not differ in the numbers of rehospitalizations and acute care visits, or in measures of physical and mental growth. We conclude that early discharge of very-low-birth-weight infants, with follow-up care in the home by a nurse specialist, is safe and cost effective.     

Elevated levels of lipopolysaccharide-binding protein and soluble CD14 in plasma in neonatal early-onset sepsis

No data on lipopolysaccharide-binding protein (LBP) in newborns with sepsis have been available up to now. We therefore determined levels of LBP and soluble CD14 (sCD14) in plasma of healthy and septic neonates in order to evaluate their potential diagnostic role. The study included prospectively collected patient samples of two recently published studies on cytokine expression in neonatal sepsis. Twenty-nine septic patients were enrolled in the present analysis. Samples--either cord blood or peripheral blood--from patients admitted within the first 24 h of life for suspicion of sepsis and cord blood samples of a control group of 40 healthy mature infants delivered spontaneously were analyzed. For seven patients of the septic group, a second sample collected between 24 and 48 h of life was available. Levels of sCD14 and LBP in plasma were determined by an enzyme immunoassay using recombinant CD14 and LBP as standards. LBP and sCD14 were correlated to cytokine plasma levels. In septic neonates, LBP (median, 36.6 versus 7.8 microg/ml; P < 0.001) and sCD14 (median, 0.42 versus 0.28 microg/ml; P < 0.001) levels were highly elevated when compared to those of healthy neonates and strongly correlated to granulocyte colony-stimulating factor (G-CSF), interleukin-1beta (IL-1beta), IL-6, and IL-8 levels. LBP levels in septic neonates analyzed between 24 and 48 h of life even increased when compared to samples obtained at or shortly after delivery (median, 36.6 versus 60 microg/ml; P = 0.038). In summary, levels of LBP in plasma of neonates with early-onset sepsis are significantly elevated; the elevated plasma levels seem to persist for more than 24 h, which could provide the clinician with a prolonged time period to identify the newborn with bacterial sepsis.     

Pathophysiologic mechanisms causing sleep apnea and hypoventilation in infants

Complete absence of chemoreception in the medulla is characterized by sustained hypoventilation. Except for the first months of life, this deficit does not, of itself, cause apnea. Both in infants who lack central chemical drive, as well as those who are only partly deficient, it is necessary to invoke at least one further pathophysiologic event. Various alterations in gas exchange, especially during sleep, which promote hypoxemia can contribute to a positive feedback effect on ventilation. If gas exchange is further impeded by upper-airway obstruction, only a massive arousal response separates the infant from death.