Modulation of neonatal myelopoiesis in newborn rats after 7 days' administration of either granulocyte-monocyte colony stimulating factor or interleukin-3

Single-pulse administration of either recombinant human granulocyte-monocyte colony stimulating factor or recombinant human granulocyte colony stimulating factor to newborn rats has previously been demonstrated to increase the peripheral neutrophil count and modulate bone marrow (BM) neutrophil pools. In our present study, we investigated the effects of 7 d of either recombinant murine granulocyte-monocyte colony stimulating factor (rmGM-CSF) (75 micrograms/kg/d) or recombinant murine IL-3 (rm IL-3) (10 micrograms/kg/d) on newborn rat myelopoiesis. Sprague Dawley newborn rats (greater than or equal to 24 h) were injected (intraperitoneally) daily for 7 d with either rmGM-CSF, rmIL-3, or PBS/BSA. rmGM-CSF induced a significant increase in the peripheral neutrophil count on d 3 (p less than 0.03) and d 7 (p less than 0.001) (75% increase). Additionally, rmGM-CSF induced a 50% increase in the BM neutrophil storage pool (p less than 0.025). rmIL-3 increased the BM colony forming unit-granulocyte monocyte pool (p less than 0.001); however, it failed to increase the peripheral neutrophil count or BM neutrophil storage pool. Neither CSF increased the BM neutrophil proliferative pool or BM colony forming unit-granulocyte monocyte proliferative rate. Additionally, 7 d of rmGM-CSF with or without antibiotics did not synergistically alter the mortality rate after group B streptococcol inoculation. This study suggests that rmIL-3 appears to stimulate more neonatal myeloid committed progenitor cell activity compared with rmGM-CSF. Optimal modulation of neonatal myelopoiesis may require the use of a sequential combination of hematopoietic CSF, namely an early-acting CSF followed by a more lineage myeloid-specific CSF.     

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.     

A trial of recombinant human granulocyte colony stimulating factor for the treatment of very low birthweight infants with presumed sepsis and neutropenia

OBJECTIVES: The primary objective was to investigate the safety of recombinant human granulocyte colony stimulating factor (rhG-CSF) for the treatment of very low birthweight infants (VLBW) with sepsis and relative neutropenia, specifically with regard to worsening of respiratory distress and thrombocytopenia and all cause mortality. Secondary objectives were to evaluate duration of ventilation, intensive care, and antibiotic use as markers of efficacy. DESIGN: Neonates (< or = 28 days) in intensive care, with birth weights of 500-1500 g, absolute neutrophil count (ANC) of < or = 5 x 10(9)/l, and clinical evidence of sepsis, were randomly assigned to receive either rhG-CSF (10 microg/kg/day) administered intravenously (n = 13), or placebo (n = 15) for a maximum of 14 days, in addition to standard treatment and antibiotics. All adverse events, oxygenation index, incidence of thrombocytopenia, all cause mortality, duration of ventilation, intensive care and antibiotic treatment, and ANC recovery were compared between the two groups. RESULTS: Adverse events and oxygenation index were not increased by, and thrombocytopenia was not attributable to, treatment with rhG-CSF. At 6 and 12 months postmenstrual age, there were significantly fewer deaths in the group receiving rhG-CSF (1/13 v 7/15; p < or = 0.038). There was a non-significant trend towards a reduction in duration of ventilation, intensive care, and antibiotic use in the rhG-CSF group. There was a significantly more rapid increase in ANC in the rhG-CSF treated babies (p < 0.001). CONCLUSIONS: In a small randomised placebo controlled trial in a highly selected group of neonates, adjuvant treatment with rhG-CSF increased ANC rapidly, and no treatment related adverse events were identified. Mortality at 6 and 12 months postmenstrual age was significantly lower in the treatment group. A large trial investigating efficacy in a similar group of neonates is warranted.     

Sequential administration of interleukin-6 and granulocyte-colony stimulating factor in newborn rats: modulation of newborn granulopoiesis and thrombopoiesis.

During states of increased demand, neonatal host defense is characterized by dysregulation of granulopoiesis, resulting in a high incidence of neutropenia. This study investigated the modulation of neonatal rat hematopoiesis by 14-d administration of recombinant human (rh) IL-6, rh-granulocyte-colony stimulating factor (G-CSF), or sequential combination of rhIL-6 and rhG-CSF. Specifically, newborn Sprague-Dawley rats were treated with either rhIL-6 (5 micrograms/kg/d for 14 d), rhG-CSF (5 micrograms/kg/d for 14 d), rhIL-6 for 7 d followed by rhG-CSF for 7 d, PBS/BSA for 7 d followed by rhG-CSF for 7 d, or PBS/BSA for 14 d. RhIL-6 alone significantly increased the peripheral platelet count during the latter part of the 2nd wk of administration (d 13: 980 +/- 42 versus 716 +/- 23 x 10(3)/mm3) (p = less than 0.001) (mean +/- SEM). Treatment with rhIL-6 for 7 d followed by rhG-CSF significantly increased the peripheral neutrophil count compared with 7 d of PBS/BSA and 7 d of G-CSF (d 14 absolute neutrophil count 4888 +/- 12 versus 2720 +/- 317/mm3) (p = less than 0.05). Similarly, sequential rhIL-6/rhG-CSF significantly increased the d-14 bone marrow neutrophil storage pool (9873 +/- 882 versus 3564 +/- 159/mm3) (p = less than 0.005). Lastly, sequential rhIL-6/rhG-CSF induced the highest increase in bone marrow (p less than 0.01) and liver/spleen CFU-GM pool (p less than 0.001) compared with any other treatment group. These studies suggest that rhIL-6 alone is associated with a significant increase in the neonatal platelet count.(ABSTRACT TRUNCATED AT 250 WORDS)     

The effect of administration of immunoglobulin to newborn rats with Escherichia coli sepsis and meningitis

Newborn rats 24-36 h old were injected transthoracically with various doses of Escherichia coli K1. Eighty-six of 92 rats which received 10(4) colony-forming units/g body weight were dead within 48 h. Two h after injection, E. coli were recovered from the blood of six of six rats and from the cerebrospinal fluid of two of six. Sixteen h after injection, E. coli were recovered from all blood (7/7) and spinal fluid (11/11) specimens cultured. Animals inoculated with 10(4) E. coli/g exhibited neutropenia and depletion of the neutrophil storage pool. In other studies, newborn rats inoculated with E. coli were injected intraperitoneally with various doses of human serum immunoglobulin, modified for intravenous use (MISG). One hundred percent (25/25) injected with 1500 mg/kg lived. In contrast to infected animals injected with albumin (controls), MISG recipients did not develop neutropenia nor did they deplete their neutrophil reserves. The effects of treating infected animals with MISG, antibiotics, or a combination of antibiotics plus MISG were compared. When administered within 2 h after the E. coli, all treatments resulted in survival rates of over 75%. However, when delayed for 6 h, 63% (17/27) of antibiotic recipients, 50% (12/24) of MISG recipients, and 91% (30/33) of those receiving both treatments lived (p less than 0.01 versus antibiotics or MISG).     

Granulocytic stem cell (CFUc) proliferation in experimental group B streptococcal sepsis

Adult rats infected with group B streptococci (GBS) develop neutrophilia and display a marked increase in granulocytic stem cells (CFUc). In contrast, infected neonatal rats develop a profound neutropenia and their CFUc do not increase. In order to better understand this phenomenon, we assessed the CFUc proliferative rate in control and infected adult and neonatal rats using the technique of [3H]-thymidine suicide. Beginning only 3 h after GBS inoculation, adult rats increased CFUc proliferative activity, as illustrated by an increase in thymidine suicide, from 38 +/- 2% cell kill in control animals to 70 +/- 2% when infected (mean + S.E., P less than 0.001). In contrast, the CFUc thymidine suicide rate did not increase in infected neonates. It was noted, however, that the baseline CFUc thymidine suicide rate in uninfected neonatal rats exceeded the rate in uninfected adult rats by 2-3-fold. The CFUc thymidine suicide rate was therefore determined in uninfected premature (74 +/- 1%), newborn (70 +/- 2%), 1-wk-old (70 +/- 1%), 6-wk-old (32 +/- 1%) and 6-month-old (37 +/- 3%) rats. These findings suggest that the proliferative rate of granulocytic stem cells is already maximal or near maximal in noninfected neonatal animals. In contrast to adults, the neonates' granulocyte production from stem cells can not significantly increase, even if bacterial infection is present.     

Modulation of neonatal rat myeloid kinetics resulting in peripheral neutrophilia by single pulse administration of Rh granulocyte-macrophage colony-stimulating factor and Rh granulocyte colony-stimulating factor.

Rh granulocyte-macrophage (GM) colony-stimulating factor (CSF) and rh granulocyte (G) CSF have been demonstrated to induce proliferation and maturation of myeloid stem cells and release of mature polymorphonucleocytes (PMNs) from human and animal adult bone marrows. Unfortunately, reduced bone marrow progenitor cells, neutrophil storage pool (NSP) depletion and peripheral neutropenia are characteristic of human and animal newborn bone marrows. We investigated the effect of administering intraperitoneal rhGM-CSF and rhG-CSF to Sprague-Dawley newborn rats (less than 36 h). Newborn rats treated with intraperitoneal CSF (3.0 micrograms/kg) demonstrated significant leukocytosis at 6 and 24 h: rhGM-CSF vs. control, WBC (10(3)/mm3), at 6 h, 8.0 +/- 0.5 vs 4.3 +/- 0.9 (p less than or equal to 0.003), and at 24 h, 7.7 +/- 1.7 vs. 3.8 +/- 0.2 (p less than or equal to 0.008); rhG-CSF vs. control WBC (10(3)/mm3) at 6 h, 6.6 +/- 1.2 vs 4.3 +/- 0.1 (p less than or equal to 0.03), and at 24 h, 8.1 +/- 0.2 vs. 3.75 +/- 0.2 (p less than or equal to 0.003). The absolute neutrophil count was also significantly elevated at 6 h following intraperitoneal CSF (3.0 micrograms/kg): RhGM-CSF vs. control 1,827 +/- 25 vs. 379 +/- 10 (p less than or equal to 0.001); rhG-CSF vs. control, 1,698 +/- 40 vs. 371 +/- 10.1 (p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Rifampin and penicillin for the elimination of group B streptococci in nasally colonized infant rats

Although multiple antibiotic strategies to eradicate group B streptococci (GBS) from colonized infants and women have been utilized, no regimen has been successful in eliminating GBS carriage reliably. Because rifampin has been successful in terminating nasopharyngeal colonization with other bacteria, we tested both the in vitro sensitivity of GBS to rifampin and the in vivo efficacy of rifampin in eliminating GBS from a new animal model of nasally colonized infant rats. The minimal inhibitory concentration of rifampin for 18 clinically derived strains of type III GBS ranged from 0.1 to 0.4 micrograms/ml. Atraumatic nasal inoculation of infant rats with 10(6)-10(7) colony forming units of GBS twice daily for 4 days resulted in heavy asymptomatic carriage for at least 10 days. Colonized animals were divided into four treatment groups: saline, oral rifampin, intraperitoneal penicillin, or oral rifampin plus intraperitoneal penicillin. Treatment was administered every 12 h for 4 days. All 78 saline-treated controls and 47 of 52 (90.4%) penicillin-treated animals had continued GBS carriage 36 h after completion of therapy. In contrast, only 18 of 52 (34.6%) rifampin-treated animals and seven of 54 (13.0%) rifampin plus penicillin-treated animals remained GBS-positive. No rifampin-resistant GBS were detected. Combination rifampin plus penicillin therapy was significantly more effective in terminating GBS carriage compared to saline or penicillin alone (p less than 0.0001) or to rifampin (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

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.     

Newborn colonization and antibiotic susceptibility patterns of <Emphasis Type="Italic">Streptococcus agalactiae</Emphasis> at the University of Gondar Referral Hospital,Northwest Ethiopia

Background

Group B Streptococcus (GBS) that asymptomatically colonizing the recto-vaginal area of women is the most important cause of neonatal colonization. There is paucity of evidence about newborn colonization with GBS in Ethiopia. Thus, this study was aimed to determine the prevalence of newborn colonization with GBS, antibiotic susceptibility patterns of the isolates and associated risk factors at the University of Gondar Referral Hospital in Northwest Ethiopia

Methods

A prospective cross sectional study was conducted from December 2016 to November 2017. A total of 1,155 swabs from nasal, ear and umbilical areas of the newborns were collected from the 385 newborns. Identifications of the isolates and antibiotic susceptibility testing were done by using conventional methods.

Results

Sixty two (16.1%, 95% CI: 12.2% - 20%) of the newborns were colonized by GBS. Seven percent of the total specimens were positive for GBS. The antibiotics susceptibility rates of GBS (average of the three body sites tested) were 95.1%, 89.6%, 88.9%, 85.7%, 85.3%, 81.3%, 76.9%, 76.1%, 73.8%, and 34.4% to ampicillin, penicillin, ciprofloxacin, chloramphenicol, vancomycin, azitromycin, erythromycin, clindamycin, ceftriaxone, and tetracycline, respectively. A multilogistic regression analyses were shown that the newborns that were from mothers whose education status was below tertiary level, and newborns from mothers who were: being employed, being nullipara and multigravida were at risk for colonization with GBS.

Conclusion

Prevalence of neonatal colonization with GBS was higher than it was reported in three decades ago in Ethiopia. Ciprofloxacin, chloramphenicol, vancomycin and azithromycin were identified as the drug of choice next to ampicillin and penicillin.

     

Prevention of group B streptococcal colonization with topically applied lipoteichoic acid in a maternal-newborn mouse model

An animal model of maternal-newborn transmission of group B streptococci (GBS) was developed. Pregnant Swiss-Webster mice were colonized by applying 10(8) GBS to the oral cavity, vagina, and nipples daily for 3 days before delivery. Lipoteichoic acid (LTA) from type III GBS or phosphate buffered saline was applied topically to the oral cavity, perineum or nape of newborn mice. Cultures of newborn mice at 3 days of age revealed 35 of 75 (47%) controls and 0 of 79 animals given 2 doses of LTA (2 mg/ml) were positive for GBS at one or more sites. One to two% of control and LTA-treated mice remained culture positive at 7 days of age. None developed GBS disease and no obvious toxicity was noted. This is the first in vivo evidence that colonization with GBS can be prevented by interfering with their adherence to epithelial surfaces. LTA also prevented colonization by 60,000 GBS in the oral cavity of 1-day-old newborn mice. A minimum concentration of 0.5 mg LTA/ml was required and similar dose response curves were obtained in preventing maternal-newborn transmission or oral newborn colonization. LTA from type III GBS also protected against types Ia and II. Only 6 of 15 (40%) vaginally colonized, nonpregnant mice became noncolonized 3 days after LTA treatment. Topically applied lipoteichoic acid from group B streptococci may be a useful method of preventing GBS colonization and/or disease in human infants at birth if it is nontoxic. The method avoids the problems associated with antibiotic prophylaxis and vaccine development.     

Administration of recombinant human granulocyte-colony stimulating factor to septic neonates induces neutrophilia and enhances the neutrophil respiratory burst and β2 integrin expression Results of a randomized controlled trial

The objective of this study was to investigate the effect of treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF) on the neutrophil count and function of preterm neonates with documented sepsis. For this purpose 62 preterm neonates with proven sepsis and 19 healthy preterm ones were studied. Of the 62 patients, 27 septic neonates had an absolute neutrophil count (ANC) >5000/mm³ (group A) and were scheduled not to receive rhG-CSF and 35/62 had an ANC <5000/mm³ (n= 35) and were randomly assigned either to receive rhG-CSF (group B) or not to receive it (group C). rhG-CSF (10 μg/kg) was administered for 3 consecutive days (0, 1, 2). The ANC, plasma levels of G-CSF (ELISA), neutrophil respiratory burst activity (NRBA) and neutrophil expression of CD11a, CD11b and CD11c (flow cytometry) were measured in all septic neonates on days 0 (onset of sepsis), 1, 3 and 5 and in the healthy neonates once within the first 2 days of life. We found that on day 0, G-CSF levels of all groups of septic neonates were significantly higher than those of the healthy ones. The highest levels were observed in group A. NRBA was diminished only in groups B and C and the expression of CD11a and CD11c was reduced in all groups of septic neonates. Administration of rhG-CSF resulted in a rapid and significant increase in ANC, NRBA and CD11a, CD11b and CD11c expression that persisted throughout the follow up. Conclusion The administration of granulocyte colony stimulating factor to septic neonates significantly increases the absolute granulocyte count and enhances the neutrophil respiratory burst and β₂ integrin expression. Received: 25 March 1997 and in revised form: 5 August 1997 / Accepted: 14 October 1997     

Significance of radiographic findings in early-onset group B streptococcal infection.

Chest radiographs on 73 neonates with early-onset group B Streptococcus (GBS) infection were reviewed. Eighty-six percent of the infants were premature (less than 38 weeks); 68% weighed less than or equal to 1,500 g. In infants weighing less than or equal to 1,500 g, the predominant radiographic pattern was hyaline membrane disease (HMD) (80%). There was a significant increase in radiographic HMD in 1,000 to 1,500-g neonates with GBS infection (77%) when compared to a control group of infants without GBS infection (44%). Mortality in 1,000 to 1,500-g infants with GBS infection and radiographic HMD (95%) was also significantly higher than in the control group of infants with hmd HMD and no GBS infection (38%). In larger premature and full-term infants, the radiographic findings were not specific and also were not helpful in distinguishing GBS infection from other newborn respiratory disorders.     

Early-onset neonatal group B streptococcal infections in New Zealand 1998-1999

OBJECTIVE: To determine in New Zealand infants the attack rates, risk factors, preventive policies, strain serotype and antibiotic susceptibilities of early-onset neonatal group B streptococcus (GBS) infection. METHOD: A 2-year prospective active surveillance study was conducted in New Zealand's 19 neonatal units. Cases had to present within 48 h of delivery, be unwell, possess abnormal haematological indices and have GBS isolated from sterile sites. RESULTS: Of the 112 402 infants born in New Zealand during 1998-1999, 56 had early-onset GBS infection, an attack rate of 0.5 per 1000 live births (95% confidence interval [CI] 0.38, 0.65). Seven had meningitis and there was one death (case fatality rate of 1.8%; upper 95% CI 9.5%). Univariate analysis identified young maternal age, parity, preterm labour, prolonged membrane rupture, maternal fever and assisted delivery as risk factors. Preventive policies for GBS were reported by 14 (74%) obstetric centres associated with neonatal units. Of the 56 cases, five (9%) were born to mothers receiving intrapartum antibiotics, 32 (57%) had mothers with risk factors but were not treated with antibiotics, and 19 (34%) were born to mothers without identifiable risk factors for GBS prevention. Serotypes Ia and III predominated, while two isolates were resistant to erythromycin and/or clindamycin. CONCLUSIONS: Rates of early-onset GBS infection are similar to other countries following the introduction of prevention policies. Further reductions are possible with full implementation of these guidelines. Meanwhile, emergence of antibiotic resistance complicates the management of women with penicillin allergy. Vaccine development therefore remains a priority.     

Protective value of gamma globulin preparations against group B streptococcal infections in chick embryos and mice

The protective value of pooled human gamma globulin (GG) and a group B streptococcal immune globulin (GBSIG) was studiedf in a chick embryo and a murine model of group B streptococcal (GBS) infection. Chick embryos were protected by the IV administration of 0.4 to 0.8 mg of GG from three manufacturers against IV challenge with type Ia GBS. Two of three GG preparations at doses of 0.4 to 1.65 mg protected chick embryos against type III, but 1.65 mg of all three preparations failed to protect against GBS types Ib and II. MIce were protected from lethal IP challenges with types Ia and Ib by the prior IM inoculation of three and two of the three GG preparations at doses of 0.5 to 1.0 mg, respectively. Administration IM of 1 mg of GG failed to protect mice against types II and III. The IV administration of 0.2 mg of GBSIG protected chick embryos against IV inoculation with GBS types Ia, Ib, II, and III. Administration IM of 0.5 mg of GBSIG protected mice against IP challenges with types Ia, Ib, and II, but not with type III. The IP administration of 0.25 mg of GBSIG simultaneously with type III GBS protected mice, whereas GG was not protective. GBSIG should undergo clinical trials for the prevention of GBS infections and their recurrences and as a possible adjunct to antibiotic and supportive therapy of severe GBS infections.     

The use of inhaled corticosteroid in preschool wheezers: what's the point today?

Purpura fulminans (PF) is an ominous cutaneous condition usually associated with meningococcemia. PF in the newborn is rarely reported. We report the case of a female preterm infant with extensive PF due to group B streptococcus (GBS) septicemia. She developed multi-organ system failure despite neonatal intensive care support and succumbed 9 days later. GBS, sensitive to penicillin, was isolated from the blood cultures of the mother and the infant. Invasive early GBS infection is common in the newborn and is empirically treated with prompt institution of intravenous antibiotics. PF associated with GBS is a rare cutaneous sign that must not be missed. Mortality remains high despite aggressive treatment and ICU support.     

Prevention of neonatal group B streptococcus disease in the 21st century

There have been significant reductions in early-onset neonatal group B streptococcus (GBS) disease following implementation of maternal intrapartum antibiotic prophylaxis (IAP) policies. Nevertheless, GBS remains a leading cause of neonatal sepsis in Australia and New Zealand resulting in considerable morbidity and mortality, particularly among preterm infants. In the United States, the universal screening-based approach for identifying women for IAP results in apparently lower rates of early-onset neonatal GBS infection than risk-based assessment. In addition, IAP has altered the profile of newborn infants who develop early-onset disease. Many affected infants lack the typical intrapartum risk factors for GBS infection, are born to mothers with a negative GBS screen or represent missed opportunities for prevention. Clinicians should remain alert for signs of sepsis in any newborn infant. We provide an update of GBS preventative management strategies in the perinatal period taking into account recent United States, Australian and New Zealand guidelines.     

Neonatal bacterial sepsis in a neonatal intensive care unit: A 5 year analysis

Objective : To study the pattern of neonatal sepsis in a neonatal intensive care unit (NICU) during a 5 year period and assess the relationship between maternal risk factors and early onset sepsis (EOS).
Methodology : The study reported here was a retrospective analysis of 209 episodes of septicaemia and 5 episodes of bacterial meningitis in 198 newborn infants, 22 of whom died. Eighty-one infants had EOS (≤72h) and 117 infants had late onset sepsis (LOS >72 h). All infants had clinical evidence of sepsis, a computerized haematological score for sepsis of 4 or greater, and either treatment with antibiotics for 7 days or more or had earlier death due to sepsis. The organisms causing neonatal sepsis were analyzed according to the day of onset, gestational age, birthweight and year of infection.
Results : Sepsis occurred in 5.6 per 1000 live births and 3.8% of NICU admissions. There were 81 episodes of EOS and 128 of LOS. Coagulase negative staphylococci (CONS) 38.8%, group B Streptococcus (GBS) 20.1% and Gram-negative bacilli (GNB) 20.1% were the common causes of sepsis; and GBS (50.6%) and CONS (60.9%) were the most common organisms in EOS and LOS, respectively. The mean gestational age and birthweight were heigher in babies with EOS than compared with LOS. The higher likelihood of probable rather than definite infection in infants with EOS was related to more mothers in the EOS group receiving intrapartum antibiotics. GNB infection was more common in their babies.
Conclusions : GBS and CONS were the most common causes of EOS and LOS, respectively. The use of maternal intrapartum antibiotics interferes with neonatal blood culture results. Because blood cultures are not always positive in neonatal septicaemia, a combination of clinical, haematological and other microbiological evidence should be used when diagnosing neonatal septicaemia.     

白血病患儿重组粒细胞集落刺激因子血药浓度监测及临床意义

目的研究急性白血病患儿反复应用重组粒细胞集落刺激因子(rhG-CsF)的药代动力学及其与临床的关系。方法应用酶联免疫吸附测定(ELIsA)方法检测46例白血病患儿的血清G-CSF浓度。结果获得29例患儿用rgG-CSF后的标本,其血清G-CSF浓度为(5.335±5.597)μg/L。反复应用rhG-CSF的患儿在下次用药前血清G-CSF水平恢复正常;少数未应用rgG-CSF患儿可检测到较高浓度的G-CsF。血清G-CSF浓度与粒细胞绝对计数值呈负相关(r=-0.8746,P＜0.01)。结论rhG-CSF的药代动力学中存在有粒细胞介导的清除机制,反复应用无药物蓄积作用。     

Intrapartum antibiotics and early onset neonatal sepsis caused by group B Streptococcus and by other organisms in Australia. Australasian Study Group for Neonatal Infections.

OBJECTIVE: Early onset group B streptococcal (EOGBS) infection, the major neonatal infection in industrialized countries, can be prevented by intrapartum antibiotics, but population studies are lacking. This study aimed to determine the incidence of early onset infections caused by group B Streptococcus (GBS) and other organisms in Australia and to assess intrapartum antibiotic use. DESIGN: Longitudinal, prospective surveillance of neonatal infections in Australian neonatal units from 1991 to 1997. Early onset infection defined as clinical sepsis in first 48 h after birth, with positive cultures of blood or cerebrospinal fluid or positive urine GBS antigen detection. RESULTS: The incidence of EOGBS sepsis fell from 2.0 per 1000 live births (95% confidence interval, 1.4, 2.5) in 1991 to 1993, to 1.3 (1.2, 1.4) in 1993 to 1995, to 0.5 (0.4, 0.7) in 1995 to 1997 (P < 0.0001). The incidence in Aboriginal babies was 5.2 (1.8, 8.6) in 1991 to 1993, 5.1 (3.0, 7.2) in 1993 to 1995 and 1.8 (1.1, 2.5) in 1995 to 1997 (P < 0.05). The incidence of early onset infections caused by organisms other than GBS also fell, from 1.2 per 1000 live births (0.8, 1.7) in 1991 to 1993, to 0.8 (0.7, 0.9) in 1993 to 1995 and 0.5 (0.3, 0.7) in 1995 to 1997 (P < 0.0001). In 1991, 3 of 9 study hospitals had a formal policy on intrapartum antibiotic use, whereas in 1997 all 11 hospitals had a formal policy (P=0.002). CONCLUSIONS: A steady fall in EOGBS infections in Australia from 1991 to 1997 has been associated with increasing use of intrapartum antibiotics. Increased antibiotic use is probably causal in the fall in GBS, because the incidence of early onset infections caused by other organisms has also fallen.