High intravenous doses of human immune globulin suppress neonatal group B streptococcal immunity in rats

We evaluated the effect of intravenously administered immune globulin (IVIG) on neonatal group B streptococcal (GBS) infection in vivo and in vitro. A suckling rat model was used to compare the impact of penicillin (150 mg/kg) with albumin control, high-dose IVIG (2.7 gm/kg), or low-dose IVIG (0.68 gm/kg) on survival and bacteremia. Three lots of IVIG (two standard and one hyperimmune) with varying titers of GBS type III activity were used. An opsonophagocytic assay was then employed to evaluate in vitro the effect of concentrations of penicillin (none to 2.4 micrograms/ml), IVIG (none to 20 mg/ml), organism-specific (GBS type III-specific) activity (none to 1280(-1], and quantity of organisms (10(4) to 10(6] on the killing of several strains of GBS type III. Low doses of IVIG enhanced suckling rat survival (p less than 0.0025) and bacterial clearance (p less than 0.01). High doses of IVIG did not improve survival and in fact delayed bacterial clearance (p less than 0.05) when compared with low doses. Survival and bacterial clearance increased as the GBS type III activity of the IVIG lot increased. GBS opsonophagocytosis was suppressed at all penicillin concentrations (p less than 0.01) by high levels of IVIG (20 mg/ml). High-dose IVIG suppression of GBS opsonophagocytosis decreased as type III activity of the lot increased. We speculate that high doses of nonspecific IVIG may cause blockade of neutrophil or bacterial receptors necessary for GBS immunity in neonates.     

Treatment of experimental group B streptococcal infection with hybridoma antibody

Previous studies have shown a reduction in mortality rate from 90% to zero when neonatal rats, inoculated with group B streptococci (GBS) were injected with type-specific IgM antibody. However, in those studies, the antibody was administered simultaneously with the bacteria and at the same site, unlike the situation which would exist if antibody was used clinically to treat established infection. In the present experiments, we administered antibody intraperitoneally at various intervals following intrathoracic inoculation of GBS. When antibody was administered immediately after, or up to 2 h following bacterial inoculation, all animals survived. When antibody administration was delayed for 4, 5, or 6 h, survival rates of 92, 60, and 29% were observed. When antibody administration was delayed for more than 6 h, no survival occurred. Failure of antibody to protect animals from death coincided temporally with profound depletion of the neutrophil storage pool. In other experiments, depletion of the neutrophil storage pool was produced by a separate, noninfectious mechanism (subcutaneous implantation of sterile polyvinyl sponge discs) after which animals were inoculated with GBS. Antibody did not provide protection from death in animals with neutrophil storage pool depletion.     

MODIFIED HUMAN IMMUNE SERUM GLOBULIN FOR INTRAVENOUS ADMINISTRATION: IN VITRO OPSONIC ACTIVITY AND IN VIVO PROTECTION AGAINST GROUP B STREPTOCOCCAL DISEASE IN SUCKLING RATS

ABSTRACT. Human immune serum globulin (ISG) preparations were tested in an in vivo suckling rat protection assay and an in vitro opsonophagocytic assay against various types and strains of Group B streptococci (GBS). Standard ISG provided minimal protection in suckling rats against type III GBS sepsis, whereas preparations of ISG modified for intravenous administration (MISG) provided significant protection against all strains of type III, type II and type Ia GBS tested. Although less protection was obtained against type la strains, the survival in suckling rats challenged with all types of GBS varied from 73 % to 91% with MISG therapy, as compared with 5% to 12% survival in untreated animals. In this in vivo model, MISG was protective even when administered after bacterial challenge, but had to be administered within 5 h of infection. MISG also had high in vitro opsonic activity against GBS types III and II, but was less effective with some type Ia strains. Just as MISG was more protective than ISG in vivo, it also was more opsonic in vitro. A detailed comparison of one lot of MISG with its parent ISG revealed that the modified preparation actually contained less IgG. When equivalent concentrations of affinity-purified IgG from both preparations were tested, the IgG from MISG was significantly more opsonic. Since the affinity purification procedure eliminated the possibility that IgM or substances introduced in the modification process were actually responsible for the enhanced bactericidal activity, it appears that the individual IgG molecules in MISG may be more effective. These studies suggest that MISG which has been modified by reduction and alkylation for intravenous administration may provide a valuable adjunct to chemotherapy in the treatment of GBS disease in the neonate.     

Prophylactic or simultaneous administration of recombinant human granulocyte colony stimulating factor in the treatment of group B streptococcal sepsis in neonatal rats.

Despite the emergence of newer antibiotic treatments, group B streptococcal infection still carries a high mortality rate in the newborn and is characterized by reduced neutrophil proliferative pools, neutrophil storage pools, neutropenia, and polymorphonuclear cell dysfunction. Recombinant human granulocyte-colony stimulating factor (rhG-CSF) has recently been demonstrated to induce neutrophilia and modulate neutrophil proliferative pools and neutrophil storage pools in the newborn rat. We therefore investigated the adjuvant effect of rhG-CSF given to group B streptococcus (GBS) septic Sprague-Dawley newborn (less than 36 h) rats treated with and without antibiotic therapy. After inoculation of GBS, a GBS survival curve established the LD50 at 50 h to be approximately 3 X 10(6) organisms/gm. Newborn rats were divided into four treatment groups after GBS inoculation. rhG-CSF was administered at the same time as GBS inoculation. At 24 h, there was approximately 100% survival in all groups. However, by 72 h after GBS inoculation, there was a significant difference in survival. Group 1, PBS/Alb, had a survival rate of 4%; group 2, rhG-CSF, 9%; group 3, antibiotics, 28%; and group 4, antibiotics plus rhG-CSF, 91% (p less than or equal to 0.001). Additionally, when rhG-CSF was administered prophylactically (6 h before GBS), a similar significant synergistic effect in survival was demonstrated with granulocyte colony stimulating factor plus antibiotics versus antibiotics alone (70 versus 10%) (p less than or equal to 0.01). These preliminary data suggest that either simultaneous or prophylactic pulse administration of rhG-CSF may have a synergistic and protective effect on survival in antibiotic-treated experimental GBS in the neonatal rat.     

Transplacental or enteral transfer of maternal immunization-induced antibody protects suckling rats from type III group B streptococcal infection

Deficiency of maternal group B streptococcal (GBS) type-specific IgG increases neonatal susceptibility to GBS infection. We asked if immunization-induced maternal type III GBS opsonic antibody transferred prenatally (via placenta) or postnatally (via breast milk) would affect suckling rat survival after GBS infection. Pregnant immunized dams with type III GBS opsonic antibody (20 through 320 dil-1) and nonimmunized dams without GBS antibody were matched (n = 16). Half of each litter was cross-suckled to a matching dam creating four pup groups with different exposure to maternal type III GBS opsonic antibody: none, postnatal, prenatal, and combined (pre- and postnatal). After infection with type III GBS, group survival (n) was 41% (51), 66% (47), 98% (43), and 98% (47), respectively. Type III GBS opsonic antibody in surviving pups was directly related to their immunized dam's antibody either postnatally (R = 0.85), prenatally (R = 0.84), or combined (R = 0.81). Pups exposed postnatally to high titers (80 to 320 dilution-1) of type III GBS opsonic antibody survived more often than those exposed to low titers (20 to 40 dil-1) (p less than 0.03). Immunization-induced maternal type III GBS opsonic antibody is transferred pre- and postnatally and results in improved neonatal survival after GBS infection. Survival of pups exposed to postnatal antibody appears related to the concentration of maternal type III GBS opsonic antibody. Breast milk with high titers of GBS type-specific antibody may modify the course of GBS infection. GBS vaccines and strategies could be tested in this model.     

Fetal dexamethasone exposure affects basal ornithine decarboxylase activity in developing rat brain regions and alters acute responses to hypoxia and maternal separation

Although glucocorticoids are widely used to stimulate fetal/neonatal lung function, they also interfere with cellular development in the central nervous system. Dexamethasone was administered to pregnant rats in late gestation at a dose (0.8 mg/kg) that lies just above the threshold for stimulation of lung surfactant synthesis, and the impact on ornithine decarboxylase (ODC) was evaluated in three brain regions. Dexamethasone treatment produced an initial inhibition of basal ODC activity followed by postnatal elevations, a pattern known to be associated with delays in cell replication and differentiation. Dexamethasone also interfered with the ability of the 1-day-old neonate to turn off ODC acutely in response to a 2-h period of maternal separation; as this response conserves energy in the absence of the dam, the effect of dexamethasone is maladaptive. Additionally, dexamethasone sensitized the neonatal brain to hypoxia: the acute increase of ODC associated with a 2-h exposure to 7% O2 was exacerbated in 8-day-old rats exposed to dexamethasone prenatally. These results suggest that administration of dexamethasone, in doses that promote respiratory competence, delays cell development in the central nervous system and renders the brain more vulnerable to adverse neonatal conditions, such as maternal separation or hypoxia.     

Effects of postnatal dexamethasone on oxygen toxicity in neonatal rats

We investigated the effect of timing of early postnatal dexamethasone on survival of hyperoxia-exposed neonatal rats. Pups <24 h old were treated with a tapering course of dexamethasone or saline beginning either prior to exposure (day 0), or after 2, 4, or 6 days of > or =98% O2 (n=11-14) or air (n=8-11). Exposures were continued for 14 days. By day 14, day 0 pups had poor survival regardless of the exposure (14% in O2, 13% in air). Survival of pups treated with dexamethasone after 2, 4 and 6 days of O2 exposure was significantly higher at 14 days (50, 86 and 79%, respectively) compared to saline O2 controls (9%, p < 0.001 for each). Pulmonary biochemical analyses were conducted after exposure for 7 days in rat pups treated with dexamethasone or saline beginning after 4 days of exposure to air or O2 (n=11-12 for each group). While pups treated with dexamethasone showed greatly improved survival compared to O2 controls, there was no decrease in neutrophil influx into the lung as measured by lung myeloperoxidase and neutrophil counts in histologic specimens and lavage fluid. Catalase, glutathione peroxidase, total and manganese superoxide dismutase activities as well as manganese superoxide dismutase (MnSOD) mRNA expression were elevated in both O2 groups after 7 days compared to the air groups (p < 0.05) and MnSOD mRNA expression was elevated in the O2/dexamethasone group, but there were no differences between dexamethasone and saline groups in O2. Thus, this study indicates that the timing of dexamethasone administration is crucial. Mechanisms other than increases in antioxidant enzymes or decreases in lung neutrophils underlie the ability of dexamethasone to improve survival of these neonatal rats.     

Monoclonal antibody 2-2-B kills K1-positive Escherichia coli in conjunction with cord blood neutrophils and sera, but not with spinal fluid

In conjunction with 400 ng/ml murine monoclonal antibody of the IgM class, cord neutrophils were able to kill K1-positive Escherichia coli in an in vitro opsonophagocytic assay. Neither adult nor cord neutrophils mediated bacterial killing in the absence of this monoclonal antibody. This bactericidal capacity was observed with eight of 11 (73%) but not all cord neutrophil samples, and under conditions of bacteria to neutrophil ratios as high as 15:1. Increasing the monoclonal antibody concentration up to 12 micrograms/ml paradoxically resulted in significantly lower amounts of bacterial killing. All 11 cord serum samples had sufficient complement activity to permit this monoclonal antibody to function; however, neonatal cerebrospinal fluid was not an effective complement source. We conclude that this monoclonal antibody may be a useful adjunct to conventional therapy of invasive disease caused by K1-positive E. coli; but it would have to work at the bacteremic phase of infection.     

Advances in Burkholderia cepacia complex

Burkholderia cepacia is an important opportunistic pathogen in certain compromised hosts, particularly those with either cystic fibrosis (CF) or chronic granulomatous disease. The "family" of bacteria known as B. cepacia is highly heterogeneous and is composed of at least nine discrete species or genomovars, constituting the B. cepacia complex. Bacteria from the B. cepacia complex are particularly virulent in susceptible hosts, often causing necrotising invasive infection and death. Whereas the microbial determinants of virulence in B. cepacia complex are currently not defined, the bacteria appear to have features facilitating survival within host cells. Burkholderia cepacia is highly resistant to antibiotics and to neutrophil-mediated non-oxidative killing; infection should be treated with combination antimicrobial therapy. Burkholderia cepacia can spread from one CF patient to another. Transmission appears to be facilitated by close personal contact and by certain bacterial factors.     

Neonatal group B streptococcal infection in South Bedfordshire, 1993-1998

BACKGROUND: Group B streptococcus (GBS) is now the leading cause of neonatal bacterial sepsis in the western world. The incidence of GBS infection in the United States has been determined, and guidelines produced and implemented for the prevention of neonatal infection. Neither incidence nor guidelines are currently established in the United Kingdom. AIM: To define the pattern of neonatal infection within one hospital (Luton and Dunstable Hospital). METHOD: A six year retrospective analysis was performed. RESULT: An incidence of early onset GBS of 1.15 per 1000 deliveries, comparable with that documented in the United States, was found.     

Dose-related protective efficacy of immunoglobulins in experimentally induced group B streptococcal infection

This study investigates the dose-dependent effect of administration of commercially available intravenous immunoglobulins (IVIG) on the survival of newborn rats experimentally infected with group B streptococci (GBS). The opsonic activity of various concentrations of IVIG in vitro was determined by examination of opsonophagocytosis of GBS by peritoneal macrophages and bacterial killing by blood neutrophils. The best survival was observed in newborn rats who received immunoglobulins at doses of 250, 500 and 1000 mg/kg of bodyweight. The survival of animals that received either 125 mg/kg or 2.5 g/kg of immunoglobulins was no better than that of animals who received no immunoglobulins. The maximal phagocytosis and bacterial killing were observed at in vitro immunoglobulin concentrations ranging from 32 to 250 mg/dL (these in vitro concentrations may correspond roughly to in vivo administration doses ranging from 150 to 1200 mg/kg). These doses are comparable to the doses of IVIG currently administered to neonates. However use of very high doses may be harmful to babies since the high concentration of non-specific immunoglobulins inhibited in vitro phagocytosis and bacterial killing by phagocytes.     

Early postnatal dexamethasone treatment and increased incidence of cerebral palsy

OBJECTIVE: To study the long term neurodevelopmental outcome of children who participated in a randomised, double blind, placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease. METHODS: The original study compared a three day course of dexamethasone (n = 132) with a saline placebo (n = 116) administered from before 12 hours of age in preterm infants, who were ventilated for respiratory distress syndrome and had received surfactant treatment. Dexamethasone treatment was associated with an increased incidence of hypertension, hyperglycaemia, and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality. A total of 195 infants survived to discharge and five died later. Follow up data were obtained on 159 of 190 survivors at a mean (SD) age of 53 (18) months. RESULTS: No differences were found between the groups in terms of perinatal or neonatal course, antenatal steroid administration, severity of initial disease, or major neonatal morbidity. Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo (39/80 (49%) v. 12/79 (15%) respectively; odds ratio (OR) 4.62, 95% confidence interval (95% CI) 2.38 to 8.98). The most common form of cerebral palsy was spastic diplegia (incidence 22/80 (28%) v. 5/79 (6%) in dexamethasone and placebo treated infants respectively; OR 4.45, 95% CI 1.95 to 10.15). Developmental delay was significantly more common in the dexamethasone treated group (44/80 (55%)) than in the placebo treated group (23/79 (29%); OR 2. 87, 95% CI 1.53 to 5.38). Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group, although these differences were not statistically significant. Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period; all 11 had received dexamethasone. Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome. CONCLUSIONS: A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay.     

Lack of effectiveness of dexamethasone in neonatal bacterial meningitis

A clinical trial was conducted to determine whether dexamethasone as adjunctive therapy alters the outcome of bacterial meningitis in neonates. Fifty-two full-term neonates with bacterial meningitis were enrolled in a prospective study. Infants were alternately assigned to receive either dexamethasone or not. Twenty-seven received dexamethasone in addition to standard antibiotic treatment and 25 received antibiotics alone. Dexamethasone therapy was started 10–15 min before the first dose of antibiotics in a dose of 0.15 mg/kg per 6 h for 4 days. Baseline characteristics, clinical and laboratory features in the two groups were virtually similar. Both groups showed a similar clinical response and similar frequency of mortality and sequelae. Six (22%) babies in the treatment group died compared to 7 (28%) in the control group (P = 0.87). At follow up examinations up to the age of 2 years, 6 (30%) of dexamethasone recipients and 7 (39%) of the control group had mild or moderate/severe neurological sequelae. Audiological sequelae were seen in two neonates in the dexamethasone group compared to one in the control group. Conclusion Adjunctive dexamethasone therapy does not improve the outcome of neonatal bacterial meningitis. Received: 22 December 1997 / Accepted: 14 March 1998     

Failure of rifampin to eradicate group B streptococcal colonization in infants

BACKGROUND: Mucous membrane colonization with group B streptococci (GBS) frequently persists in infants after treatment of invasive infection and may be associated with recurrent disease. OBJECTIVE: To determine the frequency with which GBS colonization persists at mucous membrane sites after treatment of invasive early or late onset infection and to determine the efficacy of oral rifampin in eradicating colonization in these infants and their mothers. METHODS: Cultures for isolation of GBS were obtained from infants and their mothers after completion of the infant's parenteral therapy, 1 week later when rifampin therapy was initiated and at approximately 1 and 4 weeks after completion of rifampin therapy. Rifampin was administered (10-mg/kg dose; maximum, 600 mg) twice daily for 4 days. RESULTS: Ten of 21 infants (48%) and 13 (65%) of their 20 mothers were colonized with GBS at throat or rectal (infant) or vaginal, rectal or breast milk (mother) sites before rifampin was initiated. One week or less after rifampin treatment, 7 (70%) infants and 4 (31%) mothers remained colonized with GBS. At study completion 6 infants and 7 mothers had GBS colonization. Persistent colonization was not related to GBS serotype, to initial rifampin minimal inhibitory concentration or to the development of rifampin resistant strains. CONCLUSIONS: Rifampin treatment for four days utilized as a single agent after completion of parenteral therapy failed to reliably eradicate GBS colonization in infants.     

Management of asymptomatic, term gestation neonates born to mothers treated with intrapartum antibiotics

Intrapartum antibiotics are frequently administered to parturient women for suspected chorioamnionitis to treat infection in the mother and to prevent or treat infection in the baby. We sent a questionnaire to the 150 United States fellowship program directors in neonatology and pediatric infectious disease, focusing on recommendations for evaluation and therapy of apparently healthy, pretreated, term gestation infants. Eighty-three (55%) of the completed responses were analyzed. Sixteen (19%) respondents do no initial laboratory evaluation but simply observe the baby, 65 (78%) take a complete blood count as well as a platelet count, 59 (71%) obtain blood cultures, 41 (49%) check urine antigen for Group B Streptococcus (GBS) and 23 (28%) perform a lumbar puncture. Only 39% of respondents would begin antibiotic therapy for all pretreated infants. If the evaluation were unremarkable 65 directors would treat for less than or equal to 3 days. If only the urine GBS antigen were positive 47 would treat for greater than or equal to 7 days, while if an elevated immature neutrophil:total neutrophil ratio were the sole abnormality 19 would treat for greater than or equal to 7 days. Forty-four respondents thought that a combination of an elevated immature neutrophil:total neutrophil ratio and a positive urine GBS antigen should always be considered indicative of bacteremia. Given a different scenario, that of a mother treated with intrapartum antibiotics because of a positive cervical culture for GBS and a risk factor (e.g. temperature greater than or equal to 38 degrees C), 58 respondents would begin antibiotics. There is no consensus regarding management of pretreated, healthy appearing, term gestation neonates.     

Perinatal infection with Group B streptococci

Group B streptococcus (GBS) is a major cause of severe bacterial infection in newborns. Early neonatal GBS infection can be prevented by identifying high-risk pregnancies and administering intrapartum antibiotics. In the USA, a screening strategy has been introduced resulting in a reduction in early-onset GBS infection, but no decrease in late-onset neonatal GBS disease has been noted. In many European countries, a risk-based strategy is recommended. Vaccination may, in the future, be an alternative in preventing GBS infection in newborns.     

中性粒细胞CD64和降钙素原联合检测在新生儿细菌感染早期诊断中的价值

目的探讨血清中性粒细胞CD64和降钙素原(PCT)联合检测在新生儿细菌感染早期诊断中的价值。方法将37例细菌感染新生儿依据出院诊断分为败血症组(n=15)和一般感染组(非败血症患儿;n=22);并选取同期住院非感染新生儿作为对照组(n=21)。各组新生儿均于入院后即刻抽取静脉血,采用流式细胞术检测血清中性粒细胞CD64表达,化学发光法和免疫透射比浊法分别检测血清PCT及CRP水平。结果败血症组血清中性粒细胞CD64、PCT、CRP水平高于对照组(P0.01);一般感染组中性粒细胞CD64水平高于对照组(P0.01);败血症组血清PCT、CRP水平高于一般感染组(P0.01)。中性粒细胞CD64、PCT、CRP诊断细菌感染的曲线下面积分别为0.818、0.818、0.704,均低于中性粒细胞CD64与PCT联合诊断细菌感染的曲线下面积(0.926)。中性粒细胞CD64与PCT联合检测在早期诊断新生儿感染的灵敏度和准确度分别为97.29%和89.65%,较CRP联合中性粒细胞CD64或PCT检测的灵敏度和准确度均高,较中性粒细胞CD64、PCT及CRP单项检测的灵敏度和准确度更高。结论中性粒细胞CD64、PCT联合检测能显著提高新生儿细菌感染诊断的灵敏度及准确度,有助于早期识别细菌感染。     

Neonatal escherichia coli infections: concerns regarding resistance to current therapy

Currently recommended antibiotic treatment of suspected neonatal sepsis is ampicillin and an aminoglycoside. Recently, we observed increasing ampicillin and gentamicin resistance in strains of Escherichia coli isolated from neonates at our institution. We therefore reviewed clinical and laboratory records of all neonates with systemic infection, hospitalized from 1994 through 1998, from whom E. coli was isolated from blood and/or cerebrospinal fluid. The influence of perinatal variables (e.g. rupture of foetal membranes > 24h, group B Streptococcus (GBS) colonization, urinary tract infection during pregnancy and the use of antepartum and/or intrapartum antibiotics), and neonatal variables (e.g. gestational age, age at onset of sepsis (early: < or = 72 h, late: >72 h), number of E. coli septic recurrences, and associated underlying medical and/or surgical conditions) on antimicrobial susceptibilities of invasive E. coli isolates was studied. Twenty-three neonates with invasive E. coli infection were identified; most [19 (83%)] presented as late-onset sepsis (LOS). Ampicillin-resistant E. coli were isolated in 75% and 53% of neonates in the early- and late-onset groups, respectively. Gentamicin resistance was found in 50% of early-onset sepsis (EOS) isolates compared with 16% in the late-onset group. Isolates from two neonates with EOS were resistant to both ampicillin and gentamicin. One neonate with EOS and three with LOS had recurrent E. coli sepsis; all isolates were ampicillin-resistant and one was gentamicin-resistant. All these neonates were initially treated with ampicillin and gentamicin. Both groups had associated underlying medical and/or surgical conditions (50% early-onset, 47% late-onset). Maternal GBS colonization occurred in 2 (50%) versus 3 (16%) of EOS and LOS cases, respectively. All GBS colonized women received intrapartum ampicillin prior to delivery. CONCLUSIONS: Ampicillin and gentamicin resistance is emerging in neonatal E. coli isolates from invasive infection. Current- empiric management of neonatal sepsis requires re-evaluation given changing antimicrobial susceptibilities.     

Diminished bactericidal capacity for group B Streptococcus in neutrophils from "stressed" and healthy neonates

This study compared the bactericidal capacity of polymorphonuclear leukocytes (PMNs) from neonates and adults for type Ic group B Streptococcus (GBS), and examined the effect of severe stress on the bactericidal capacity of PMNs from newborn infants. PMNs were obtained from three study groups: 26 adults, 13 healthy neonates (cord blood), and 29 stressed neonates. Stress was defined as an acute respiratory illness or bacterial infection requiring assisted ventilation. Bacterial killing was assessed using a fluorochrome microassay and PMNs adherent to glass coverslips. PMNs from stressed infants killed significantly fewer GBS than PMNs from adults (P less than 0.001 at both time points). PMNs from healthy infants also demonstrated reduced killing compared with adults (P less than 0.01 at 60 min; P less than 0.001 at 90 min). There was no significant difference in bacterial killing between stressed and healthy neonates and no correlation between bactericidal capacity and age at time of study, gestational age, birth weight, peripheral leukocyte count, or Apgar scores. Therefore, the bactericidal capacity for GBS by PMNs from neonates is diminished; however, it is not further compromised by stress.     

Neutrophil transfusions in the treatment of neonatal sepsis

Neonatal host defense simulates a clinical state of immunodeficiency that predisposes the preterm and term newborn to overwhelming bacterial sepsis. Defects in both the quantitative and the qualitative aspects of the neonatal phagocyte contribute significantly to the immaturity of their immune system. The neonate lacks adequate numbers of granulocyte bone marrow progenitor cells and has a decreased neutrophil storage pool and an increased tendency to peripheral neutropenia during neonatal sepsis. Additionally, the neonatal granulocyte demonstrates altered physiological function compared with that found in the adult with respect to chemotaxis, phagocytosis, oxidative metabolism, and bacterial killing. Reduced circulating immunoglobulins and impaired production of specific antibody are additional hallmarks of altered neonatal immunity. The use of adult neutrophil transfusions for the treatment of neonatal sepsis has shown promise in some clinical studies and no difference in others. Recent investigations have examined the use of intravenous gamma-globulin for prophylaxis and treatment of neonatal sepsis. The following review summarizes the state of immunodeficiency in the newborn and the potential role of polymorphonuclear leukocyte transfusions in the treatment of overwhelming neonatal bacterial sepsis.