Infection In Premature Neonates Research Articles

Fluconazole Prophylaxis of Candida Infections in Preterm Neonates

Abstract Infections belong to the most serious health problems in neonates. Invasive candidiases are one of the leading causes of mortality and morbidity in Neonatal intensive care units (NICUs). A more cautious approach is adequate when dealing with fungal infections in premature neonates. Sometimes it is necessary to cure an infection at the very beginning just before manifestation of clinical symptoms. Neonatal colonization due to Candida albicans or non-albicans Candidae predisposes to invasive candidiasis. Pregnancies complicated by preterm delivery should be considered for screening and treatment of maternal Candida colonization to decrease the occurrence of neonatal fungal colonization and its consequences. It is important to prevent infection to spread among patients and avoid complications. Prophylaxis in neonates must be safe and effective. Most authors prefer selective prophylaxis. Fluconazole is the drug of choice for prophylaxis in extremely low birth weight (ELBW) neonates. The prophylaxis is beneficial especially in NICUs with high rates of invasive candidiases. The authors describe benefits and trends in prophylaxis. They also summarize evidence on timing, dosing, and effect of fluconazole prophylaxis.

1161 Quandry Over the Use of Antifungal Prophylaxis in Preterm Infants: Survey of Current Practice in the United Kingdom

IntroductionProphylactic anti fungal use reduces the incidence of colonisation and invasive fungal infection in premature neonates. We surveyed the current regimens for the use of antifungal prophylaxis in the tertiary...

Placental Inflammatory Changes and Bacterial Infection in Premature Neonates with Respiratory Failure

Objective: to reveal a relationship of placental inflammatory changes to bacterial infection in premature neonates with respiratory failure. Material and methods. Bronchoalveolar aspirate was bacteriologically studied in 157 premature neonates with respiratory distress syndrome (NRDS); the total and differential leukocyte counts were measured in their peripheral blood. The levels of the cytokines IL-1^3, IL-4, IL-6, and TNF-a were studied in different biological fluids of mothers and their babies; the placentas were also morphologically examined. Results. An analysis of bacterial cultures from the tracheobronchial tree revealed no growth of bacterial microflora in 61.8% of cases, Enterococcus faecalis and Staphylococcus epidermidis were isolated in 6.4 and 8.3% of the infants, respectively; Staphylococcus haemolyticus, Staphylococcus capitis, Enterobacter agglomerans, and hemolytic group A Streptococcus were seen in 1.9% each; moreover, 1.3% of the newborn infants were found to have Bacillus spp., Staphylococcus aureus, Escherichia coli, Acinetobacter spp., and Serratia marcescens. Other microorganisms and a microbial association were encountered in 8.9% of cases. Placental morphological examination revealed different inflammatory changes concurrent with chronic and acute placental insufficiency. The investigation demonstrated that the maternal peripheral plasma levels of IL-1^, IL-4, IL-6, and TNF-a were within the physiological range at the end of the first period of delivery. The amniotic fluid displayed elevated IL-6 and TNF-a concentrations and normal IL-4 and IL-1e levels, suggesting that there was an intrauterine inflammatory process. Conclusion. Premature birth is associated with various placental inflammatory changes, which causes intrauterine stimulation of macrophages in the chorionic villi. Specific immune defense mechanisms that prevent the development of a fetal infectious process, i.e. the maternal infectious process, may induce preterm birth, but fail to lead to fetal and neonatal diseases. The investigation has shown that NRDS is a major disease in premature neonatal infants. Key words: intrauterine infection, premature neonates, cytokines, neonatal res piratory distress syndrome.

Anidulafungin for Neonatal Hematogenous Candida Meningoencephalitis: Identification of Candidate Regimens for Humans Using a Translational Pharmacological Approach

Hematogenous Candida meningoencephalitis (HCME) is a serious infection in premature neonates. Anidulafungin is an echinocandin antifungal agent with potent activity against Candida spp., but its efficacy and optimal regimens for human neonates with HCME are not known. A well-validated rabbit model of HCME was used to define pharmacokinetic-pharmacodynamic (PK-PD) relationships of anidulafungin. A mathematical model was fitted to the entire data set. The experimental data were bridged to humans. A population PK model was fitted to the data from human neonates receiving anidulafungin receiving a loading dose of 3 mg/kg, followed by 1.5 mg/kg/day. Monte Carlo simulations were performed to identify candidate anidulafungin regimens for humans. All untreated rabbits succumbed by ≤96 h postinoculation. The PK of anidulafungin was linear with dose-dependent penetration into the cerebrum. Anidulafungin exerted a rapid antifungal effect that was apparent in the first dosing interval. Near-maximal antifungal activity was observed with dosages of 10 to 20 mg/kg/day. The bridging studies suggested that the current regimen of first 3 mg/kg, followed by 1.5 mg/kg/day, is suboptimal. Higher dosages were associated with progressively greater antifungal effect. Anidulafungin is effective for the treatment of experimental HCME. Higher dosages than those currently used for clinical care are required for maximal antifungal effect.

Rare Case of Trichomonal Peritonitis

Rare Case of Trichomonal Peritonitis

Evolution of Mating within the Candida parapsilosis Species Group

Candida orthopsilosis and Candida metapsilosis are closely related to Candida parapsilosis, a major cause of infection in premature neonates. Mating has not been observed in these species. We show that ∼190 isolates of C. parapsilosis contain only an MTLa idiomorph at the mating-type-like locus. Here, we describe the isolation and characterization of the MTL loci from C. orthopsilosis and C. metapsilosis. Among 16 C. orthopsilosis isolates, 9 were homozygous for MTLa, 5 were homozygous for MTLα, and 2 were MTLa/α heterozygotes. The C. orthopsilosis isolates belonged to two divergent groups, as characterized by restriction patterns at MTL, which probably represent subspecies. We sequenced both idiomorphs from each group and showed that they are 95% identical and that the regulatory genes are intact. In contrast, 18 isolates of C. metapsilosis contain only MTLα idiomorphs. Our results suggest that the role of MTL in determining cell type is being eroded in the C. parapsilosis species complex. The population structure of C. orthopsilosis indicates that mating may occur. However, expression of genes in the mating signal transduction pathway does not respond to exposure to alpha factor. C. parapsilosis is also nonresponsive, even when the GTPase-activating protein gene SST2 is deleted. In addition, splicing of introns in MTLa1 and MTLa2 is defective in C. orthopsilosis. Mating is not detected. The alpha factor peptide, which is the same sequence in C. parapsilosis, C. orthopsilosis, and C. metapsilosis, can induce a mating response in Candida albicans. It is therefore likely either that mating of C. orthopsilosis takes place under certain unidentified conditions or that the mating pathway has been adapted for other functions, such as cross-species communication.

Comparison of shunt infection incidence in high-risk subgroups receiving antibiotic-impregnated versus standard shunts

Shunt infection is a morbid complication of CSF shunting. Though antibiotic-impregnated shunt (AIS) systems decrease shunt infections by preventing bacterial colonization following device implantation, their effectiveness in populations at high risk for infection has recently been disputed. We set out to determine whether the categorical switch to AIS systems at our institution has resulted in a decreased incidence of shunt infection in high-risk pediatric patients. We retrospectively reviewed the records from all pediatric patients undergoing CSF shunt procedures at The Johns Hopkins Hospital over a 10-year period between January 1997 and December 2007. During the 5.75 years prior to October 2002, all CSF shunts included standard, non-AIS catheters. During the 4.25 years after October 2002, all CSF shunts included AIS catheters. High-risk subgroups were defined a priori as prematurity (<35 weeks gestational age), shunts placed immediately post-meningitis, conversion of external ventricular drains (EVD) to shunt, and replacement of nosocomial shunt infection in patients requiring prolonged hospital stay (>1 month). A total of 544 pediatric patients underwent 1,072 shunt placement procedures (502 AIS, 570 non-AIS). Of patients with non-AIS catheters, 64 (11.2%) experienced shunt infection, whereas only 16 (3.2%) patients with AIS catheters experienced shunt infection (p<0.001). AIS versus non-AIS was associated with decreased shunt infection in premature neonates [three (5.5%) vs. seven (20.0%), p=0.030], acutely following bacterial meningitis [two (5.7%) vs. nine (25.0%), p=0.043], when converting EVD to shunts [zero (0%) vs. four (13.3%), p=0.030], and in patients with prolonged hospital stay>1 month [three (5.3%) vs. 12 (18.5%), p=0.022]. Staphylococcus aureus was the most common infectious agent for both non-AIS (81.3%) and AIS (75.0%) systems. The introduction of AIS catheters into our institutional practice has reduced the incidence of shunt infection in pediatric populations at highest risk for infection. AIS catheters are effective instruments to prevent peri-operative colonization of CSF shunt components.

Identification of Diagnostic Biomarkers for Infection in Premature Neonates

Infection is a leading cause of neonatal morbidity and mortality worldwide. Premature neonates are particularly susceptible to infection because of physiologic immaturity, comorbidity, and extraneous medical interventions. Additionally premature infants are at higher risk of progression to sepsis or severe sepsis, adverse outcomes, and antimicrobial toxicity. Currently initial diagnosis is based upon clinical suspicion accompanied by nonspecific clinical signs and is confirmed upon positive microbiologic culture results several days after institution of empiric therapy. There exists a significant need for rapid, objective, in vitro tests for diagnosis of infection in neonates who are experiencing clinical instability. We used immunoassays multiplexed on microarrays to identify differentially expressed serum proteins in clinically infected and non-infected neonates. Immunoassay arrays were effective for measurement of more than 100 cytokines in small volumes of serum available from neonates. Our analyses revealed significant alterations in levels of eight serum proteins in infected neonates that are associated with inflammation, coagulation, and fibrinolysis. Specifically P- and E-selectins, interleukin 2 soluble receptor alpha, interleukin 18, neutrophil elastase, urokinase plasminogen activator and its cognate receptor, and C-reactive protein were observed at statistically significant increased levels. Multivariate classifiers based on combinations of serum analytes exhibited better diagnostic specificity and sensitivity than single analytes. Multiplexed immunoassays of serum cytokines may have clinical utility as an adjunct for rapid diagnosis of infection and differentiation of etiologic agent in neonates with clinical decompensation.

Outbreak of invasive disease caused by methicillin-resistant Staphylococcus aureus in neonates and prevalence in the neonatal intensive care unit.

To describe an outbreak of severe invasive disease caused by methicillin-resistant Staphylococcus aureus (MRSA) and the epidemiology of MRSA in a neonatal intensive care unit during a 12-yr period from 1989 to 2001. A 40-bed, level III neonatal intensive care unit at a children's hospital that admits approximately 450 neonates each year from about 35 neighboring hospitals. All neonates infected or colonized with MRSA during the outbreak are described. All cases of MRSA infection or colonization in the neonatal intensive care unit from 1989 to 2001 were identified from the database maintained by the hospital epidemiology program. During the outbreak, 12 neonates were infected or colonized with MRSA, 11 of whom had the epidemic strain. Seven of these 11 neonates had invasive disease, including bacteremia, meningitis, or urinary tract infection, and four neonates were colonized with the epidemic strain. This outbreak was difficult to control by routine epidemiologic measures, and additional control measures, including closing the neonatal intensive care unit to new admissions and treating all infants with intranasal mupirocin, were implemented. Since the outbreak, the prevalence of MRSA in the neonatal intensive care unit has remained low. MRSA outbreaks in neonatal intensive care units can be prolonged. Aggressive infection-control measures are often necessary to terminate these outbreaks. Such efforts are essential because MRSA infections in premature neonates can cause significant morbidity and mortality.

Infection in premature neonates is not associated with higher attributable mortality, but with more neurologic sequellae

Infection in premature neonates is not associated with higher attributable mortality, but with more neurologic sequellae

Factor estimulante de colonias granulocíticas en prevención de sepsis nosocomial del prematuro: estudio doble ciego randomizado, controlado

Neonates often develop severe bacterial infections, at this age there is a failure in the quantity and quality of the phagocytic system, often associated with a neutropenia. This is usually more severe in the premature contributing to the higher mortality seen in this group. Recent publications favour the use of GCSF for the prevention of nosocomial infections. This was a prospective study to evaluate the early use of GCSF in the prevention of hospital acquired infection in preterm neonates. 34 preterms were randomized to treatment with GCSF and 34 to the placebo group. In this double blind trial there was no reduction in infections in this group of patients inspite of achieving a significant neutrophilia. Conclusions: In this trial GCSF was not useful in the prevention of nosocomial infections in premature neonates.

Candidal and bacterial bloodstream infections in premature neonates: a case-control study

Nosocomial bloodstream infections (BSI) in premature neonates are an important cause of morbidity and mortality. The early and efficient diagnosis of a neonatal BSI and the differentiation between bacterial and fungal BSI remains a challenging task. We compared the clinical features and blood test results in preterm infants with proven candidal or bacterial BSI in order to identify potential risk factors for developing a candidal BSI. Preterm infants with proven candidal BSI were significantly more prematurely born (mean age of gestation 27·7 vs. 29·8 weeks), had previously received significantly more antibiotics of multiple classes (mean 4·4 vs. 1·2) for significantly longer periods (mean 19·3 vs. 3·2 days), were ventilated more intensively, had a significantly longer stay at the neonatal intensive care unit before the onset of the BSI (mean 26·5 vs. 9·4 days), and had C-reactive protein values even higher than in preterm infants with a bacterial BSI (mean 90 vs. 71 mg l−1). The presence of thrombocytopenia (< 150 × 109 cells l−1) in all the preterm infants with candidal BSI was a significant difference. No differences were seen with regard to birth-weight, use of central intravascular catheters, total parenteral nutrition, white blood cell count and differentiation. In conclusion, candidal BSI can be strongly expected after the third week of admittance in the most premature neonates on a respirator and treated with multiple classes of antibiotics for a prolonged period of time. The presence of these risk factors in a ‘septic’ premature infant on antibiotic treatment justifies the empiric use of antifungals.

Candidal and bacterial bloodstream infections in premature neonates: a case-control study.

Nosocomial bloodstream infections (BSI) in premature neonates are an important cause of morbidity and mortality. The early and efficient diagnosis of a neonatal BSI and the differentiation between bacterial and fungal BSI remains a challenging task. We compared the clinical features and blood test results in preterm infants with proven candidal or bacterial BSI in order to identify potential risk factors for developing a candidal BSI. Preterm infants with proven candidal BSI were significantly more prematurely born (mean age of gestation 27.7 vs. 29.8 weeks), had previously received significantly more antibiotics of multiple classes (mean 4.4 vs. 1.2) for significantly longer periods (mean 19.3 vs. 3.2 days), were ventilated more intensively, had a significantly longer stay at the neonatal intensive care unit before the onset of the BSI (mean 26.5 vs. 9.4 days), and had C-reactive protein values even higher than in preterm infants with a bacterial BSI (mean 90 vs. 71 mg l(-1)). The presence of thrombocytopenia ( < 150 x 10(9) cells l(-1)) in all the preterm infants with candidal BSI was a significant difference. No differences were seen with regard to birth-weight, use of central intravascular catheters, total parenteral nutrition, white blood cell count and differentiation. In conclusion, candidal BSI can be strongly expected after the third week of admittance in the most premature neonates on a respirator and treated with multiple classes of antibiotics for a prolonged period of time. The presence of these risk factors in a 'septic' premature infant on antibiotic treatment justifies the empiric use of antifungals.

Candidal meningitis in neonates: a 10-year review.

Candidal meningitis may complicate systemic candidiasis in the premature neonate. We conducted a 10-year retrospective review of 106 cases of systemic candidiasis in neonates to define the incidence, clinical features, laboratory findings, treatment, and outcome of candidal meningitis. Twenty-three of the 106 neonates had candidal meningitis (0.4% of admissions to the neonatal intensive care unit). The median gestational age was 26.2 weeks, the median birth weight was 820 g, and the median age at the onset of illness was 8 days. Clinical disease was severe and commonly was manifested by respiratory decompensation. Findings of cerebrospinal fluid (CSF) analyses varied: pleocytosis was inconsistent, hypoglycorrhachia was common, gram staining was uniformly negative, and Candida was isolated from 17 neonates (74%). Each infant was treated with amphotericin B (median cumulative dose, 30 mg/kg); 5 also received flucytosine therapy. In conclusion, initial clinical features of candidal meningitis are indistinguishable from those of other causes of systemic infection in premature neonates, and normal CSF parameters do not exclude meningitis. Timely initiation of amphotericin B monotherapy was associated with an excellent outcome.

Microbial characteristics and severity of coagulase-negative staphylococcal septicaemia in premature neonates.

A pilot study was undertaken to assess the predictive value of characteristics possessed by coagulase-negative staphylococci in determining clinically important infection in premature neonates. No significant association was demonstrated between organism properties and clinical indices of infection. The routine use of simple measures of microbial characteristics in the assessment of neonatal septicaemia is not warranted.

Intravenous immune globulin prophylaxis of late-onset sepsis in premature neonates

To determine whether a single dose of intravenously administered immune globulin (IVIG) decreases late-onset sepsis in premature infants, we prospectively entered 753 neonates with birth weight 500 to 2000 gm, gestation ≤34 weeks, and age ≤12 hours into a multicenter, double-blind, controlled trial. Infants were randomly selected to receive a single intravenous infusion, 10 ml/kg, of either IVIG (500 mg/kg) or albumin (5 mg/kg) and were observed for 8 weeks for infection. Maternal and neonatal risk factors for infection did not differ between groups. Although serum IgG values before infusion were related to gestation ( R = 0.62), the change in serum IgG or half-life of IgG after IVIG infusion was not ( R ≤ 0.09). The serum IgG concentration was increased ( p <0.05) in IVIG-treated patients for 8 weeks. There were 88 episodes of late-onset sepsis in 79 neonates (10.5%). Causative organisms included the following: Staphylococcus epidermidis (37 episodes), Enterococcus (9), Staphylococcus aureus (7), Candida (6), Escherichia coli (6), and multiple organisms (11). Sepsis, death, and death as a result of infection were unaffected by treatment. We conclude that a single infusion of IVIG, 500 mg/kg, shortly after birth was not effective prophylaxis for late-onset infection in premature neonates. Future studies of late-onset sepsis prophylaxis should consider IVIG with known pathogen-specific antibody concentrations against organisms causing these infections, in particular S. epidermidis. (J P EDIATR 1994;125:922-30)

Infection and preterm labour

Preterm labour occurs in up to 10% of all births but is associated with 85% of perinatal deaths in otherwise normal babies and an unknown proportion of physical and mental handicap. The cause of preterm labour is usually unknown. Cases associated with multiple pregnancy, polyhydramnios or abnormalities of the uterus or cervix are in the minority. Associations have been found between preterm labour and maternal age, weight and height, cigarette smoking, parity, and other socio-economic factors.’ Recently the role of infection has been recognised as a major factor in the aetiology of preterm labour. The evidence that preterm labour is associated with genital tract infection falls into three categories; the increased incidence of puerpural sepsis following preterm delivery; the increased incidence of infection in premature neonates; and the epidemiological association between preterm labour and genital tract colonisation by various organisms. The incidence of maternal puerpural sepsis is three-fold greater following preterm labour than delivery at term. The incidence of infection in premature neonates is 5% compared to O.l-0.5% in term infants.3 This is partly a reflection of their immaturity, their increased risk of instrumentation and exposure to hospital pathogens in the neonatal intensive care unit. It is likely, however, that many of these infections are acquired in utero or during vaginal delivery. Common causes of neonatal sepsis are the group B streptococci and Escherichia coli both of which are commonly found in the vagina.