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Biomedical subjects

L B Givner

Publications and source records attributed to L B Givner.

At least 37 records · Page 2Linked to original sources

A prospective, randomized, placebo-controlled trial of penicillin in preterm premature rupture of membranes.

OBJECTIVE: Preterm premature rupture of the fetal membranes is common and frequently results in infectious complications. A prospective, randomized, controlled trial of penicillin versus placebo in preterm premature rupture of membranes is reported. The aim of the study was to determine if prophylactic antibiotics after preterm premature rupture of membranes would reduce infectious complications in the mother or neonate. STUDY DESIGN: Patients with preterm premature rupture of membranes between 21 and 37 weeks' gestation were randomized into a penicillin group that received 1 million units of benzylpenicillin intravenously every 4 hours followed by 250 mg of potassium phenoxymethyl penicillin (Pen-Vee K, Wyeth-Ayerst) orally twice daily or a placebo group before delivery. Latency period, infectious complications, and neonatal outcomes were studied. RESULTS: Patients with preterm premature rupture of membranes who received prophylactic penicillin had fewer infectious complications, including intraamniotic infection and postpartum endometritis (4 vs 11, p < 0.03), without adverse effects on the mother or fetus. CONCLUSION: Prophylactic penicillin in patients with preterm premature rupture of membranes reduces maternal infectious complications without adversely affecting the mother or newborn.

Chorioamnionitis↗

Invasive disease caused by Neisseria meningitidis relatively resistant to penicillin in North Carolina.

A case of sepsis and meningitis caused by Neisseria meningitidis with relative resistance to penicillin occurred in North Carolina in August 1992. This isolate was relatively resistant due to decreased affinity of its penicillin-binding protein 2 for penicillin. Such isolates have been reported in Spain, elsewhere in Europe, in South Africa, and in Canada, but invasive disease caused by meningococcal isolates relatively resistant to penicillin was not recognized in the United States before a preliminary report of this case in October 1992. The Centers for Disease Control and Prevention recently retrospectively identified 3 additional cases from 1991. A fifth case occurred in Kentucky in 1993. Surveillance studies of penicillin susceptibility of N. meningitidis isolates suggest such meningococci have existed sporadically in the past. Increases in prevalence and magnitude of penicillin resistance among strains of N. meningitidis would require reconsideration of current clinical practice with regard to treatment of meningococcal disease.

Amoxicillin↗

Hyperimmune human IgG or recombinant human granulocyte-macrophage colony-stimulating factor as adjunctive therapy for group B streptococcal sepsis in newborn rats.

Group B streptococcus (GBS) continues to cause considerable morbidity and death in newborn infants despite the use of antibiotics. We investigated the use of adjunctive therapies to be used with antibiotics in the treatment of neonatal sepsis, using a neonatal rat model of established GBS disease. After the development of GBS bacteremia, a human IgG preparation hyperimmune for GBS, administered with penicillin, decreased the mortality rate compared with the use of penicillin alone (14% vs 57%; p = 0.02). Similarly, recombinant human granulocyte-macrophage colony-stimulating factor, administered in a range of doses to animals with bacteremia, decreased mortality rates. The greatest effect was noted at a dose of 0.05 micrograms/kg (mortality rate 39% in combination with penicillin vs 76% for penicillin alone; p < 0.0001). Thus adjunctive therapies such as those studied here may have the potential to improve the outcome of neonatal sepsis.

Adjuvants, Immunologic↗

Meningitis due to Staphylococcus aureus in children.

Meningitis due to Staphylococcus aureus is uncommon, occurring primarily in patients with known preexisting abnormalities of the CNS (including patients who have undergone previous neurosurgery or trauma). We reviewed our experience with meningitis due to S. aureus in children seen at two medical centers. Among the 40 patients, 32 (80%) had a known predisposing abnormality of the CNS at the time of diagnosis of S. aureus meningitis; all of these 32 patients had had recent neurosurgery, most for placement or revision of a ventriculoperitoneal shunt. Eight patients had no known predisposing CNS abnormality. Four of these eight patients were known to be immunocompromised. The other four patients all had an occult CNS abnormality demonstrated during subsequent workup. Our series demonstrates that when the diagnosis of S. aureus meningitis is made in the absence of a known predisposing CNS abnormality or immunologic defect, then a timely search for an occult CNS abnormality should be undertaken.

Brain Abscess↗

Intravenous immune globulin for the prevention of nosocomial infection in low-birth-weight neonates. The Multicenter Group for the Study of Immune Globulin in Neonates.

BACKGROUND: Nosocomial infection is a major risk for premature infants with very low birth weights. One reason for their susceptibility to infection may be antibody deficiency, since there is little transfer of maternal IgG to the fetus before 32 weeks' gestation. METHODS: We conducted a multicenter, double-blind study of neonates weighing 500 to 1750 g at birth. A total of 588 neonates were randomly assigned, with stratification for birth weight, to receive periodic intravenous infusions of either immune globulin (500 mg per kilogram of body weight per day) or a placebo. Mortality, morbidity, and nosocomial infection during the next 56 days were assessed. RESULTS: The infusions were well tolerated; mild, reversible adverse reactions occurred in five infants in each group. There was a significant reduction in the risk of a first nosocomial infection in the recipients of immune globulin as compared with the placebo recipients (relative risk, 0.7; 95 percent confidence interval, 0.5 to 0.9). About 85 percent of the nosocomial infections were bacterial; the majority of these were caused by coagulase-negative staphylococci or Staphylococcus aureus. The neonates who received immune globulin had fewer mean days of hospitalization than the controls (62 vs. 68, P = 0.15); among the infants with infections, the difference in the mean length of the hospital stay was even greater (80 days vs. 101 days, P = 0.02). CONCLUSIONS: For premature infants weighing between 500 and 1750 g at birth, treatment with intravenous infusions of immune globulin is safe and reduces the risk of nosocomial infection.

Cross Infection↗

Outbreak of Candida bloodstream infections associated with retrograde medication administration in a neonatal intensive care unit.

An outbreak of candidemia involving five infants receiving total parenteral nutrition in the neonatal intensive care unit was investigated. Cultures of the intravenous fluids demonstrated that the retrograde medication syringe fluids were significantly more likely to be contaminated with Candida than were other fluids being administered to the infants (p less than 0.001). Candidemia was significantly associated with total parenteral nutrition (p = 0.04) and retrograde medication administration (p = 0.02). A survey of nursing practice found that reuse of the retrograde syringes was the most likely cause of contamination. Molecular typing showed that the strains of Candida albicans that were isolated from the bloodstream were also found in the retrograde syringes and that at least three strains of C. albicans and one strain each of Candida tropicalis and Candida parapsilosis were involved. In vitro growth curves demonstrated that Candida species had a selective growth advantage versus bacteria in the total parenteral nutrition fluid. An in vitro simulation of the retrograde medication administration system suggested that the outbreak probably developed after the frequency of changing intravenous tubing was decreased from every 24 hours to every 72 hours. The outbreak was terminated by using syringes only once and resuming intravenous tubing changes every 24 hours. Retrograde medication administration in association with total parenteral nutrition may increase the risk of Candida line infection.

Candida↗

Therapeutic use of recombinant human granulocyte-macrophage colony-stimulating factor in neonatal rats with type III group B streptococcal sepsis.

The use of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) as therapy in neonatal sepsis has been proposed because of observed defects in polymorphonuclear leukocyte (PMNL) production and function in infected neonates. Newborn rats were infected intraperitoneally (ip) with type III group B streptococcus (III-GBS) and effects of treatment with rhGM-CSF given ip 7-19 h after infection were studied. Overall mortality was 67% in controls and 37% in animals treated with rhGM-CSF (P = .003). No changes in peripheral blood PMNL number or oxidative metabolic function were found in infected or uninfected animals given rhGM-CSF compared with controls. In uninfected animals, there was an increase in the oxidative burst of peritoneal cells at 3.5 h (P = .043) and in the numbers of peritoneal cells at 3 h (P = .001) in animals receiving ip rhGM-CSF compared with controls. Phagocyte priming, cellular influx into the peritoneum, or both appear to contribute to the decreased mortality observed in this model of rhGM-CSF therapy of III-GBS disease in neonates.

Animals↗

Apparent increase in the incidence of invasive group A beta-hemolytic streptococcal disease in children.

Recently, among adults, an increase in the incidence of invasive disease caused by group A beta-hemolytic streptococci (GABS) has been noted, as has the appearance of a severe illness called "toxic shock-like syndrome," also caused by GABS. We now report an apparent increase beginning in 1987 in the incidence of invasive disease caused by GABS in children. Among these patients the manifestations were varied. One child had signs and symptoms compatible with the streptococcal toxic shock-like syndrome. Among the GABS isolates from our patients, 8 (80%) of 10 evaluated for M-protein antigens were nontypeable. Further studies will be necessary to determine the relationship between serotypes and virulence of GABS. Physicians should be aware of the possibility of an increasing incidence of invasive GABS disease in children, as well as its manifestations, which may include toxic shock-like syndrome.

Adolescent↗

Pooled human IgG hyperimmune for type III group B streptococci: evaluation against multiple strains in vitro and in experimental disease.

Because rates of morbidity and mortality due to newborn sepsis are unacceptably high, adjunctive therapies must be investigated. In the current studies, after healthy adults were immunized with type III group B streptococcal (III-GBS) capsular polysaccharide vaccine, serum was obtained from "vaccine-responders" from which a pooled human IgG preparation hyperimmune for III-GBS was prepared by ion-exchange column chromatography. This preparation, containing 549 micrograms/ml III-GBS antibody was very active functionally when evaluated against multiple III-GBS strains both in vitro in an opsonophagocytic assay using newborn sera and in a newborn rat model of III-GBS disease. The level of functional activity was dramatically higher than that of commercially available human IgG preparations for intravenous use demonstrated previously in identical assays. Human IgG preparations hyperimmune for GBS offer promise for use as adjunctive therapy of sepsis in newborns.

Animals↗

Intrapartum hepatitis B screening in a low-risk population.

Intrapartum hepatitis B surface antigen testing was performed on all laboring patients admitted to Forsyth Memorial Hospital in Winston-Salem, North Carolina from December, 1988 through November, 1989. Of the 5580 patients tested, eight patients had test results positive for hepatitis B surface antigen (overall prevalence rate of 0.14%). HBsAg was present in 0.3% of public patients and 0.08% of private patients. Of the seven patients who were not known to be positive for hepatitis B surface antigen before pregnancy, three had identifiable risk factors for hepatitis B virus. The time interval from birth to administration of hepatitis B immune globulin in the newborn averaged 13.3 hours. Patient cost per new case detected was $13,203. Intrapartum hepatitis B surface antigen screening with an assay performed once daily allows for timely administration of hepatitis B immune globulin to the newborn in accordance with recommendations of the American College of Obstetricians and Gynecologists, although some newborns receive hepatitis B immune globulin after the 12-hour birth-to-administration interval recommended by the Centers for Disease Control.

Costs and Cost Analysis↗

Human immunoglobulins for intravenous use: comparison of available preparations for group B streptococcal antibody levels, opsonic activity, and efficacy in animal models.

Currently available human immunoglobulin preparations for intravenous use (IVIGs) are being used (with antibiotics) by some physicians for therapy of sepsis in newborns. Most neonatal sepsis and/or meningitis in this country is caused by group B Streptococcus (GBS), and most of these cases are due to type III GBS (III-GBS). The killing of III-GBS in vitro is dependent on specific IgG antibody. Adequate serum levels of specific III-GBS antibody protect the exposed newborn from the development of invasive disease. Therefore, III-GBS was used as a model to evaluate the activity of three IVIG preparations available for clinical use. Specific antibody levels, in vitro opsonophagocytic killing, and protective efficacy in animal models revealed differences in activity for III-GBS between the three IVIG preparations as well as between IVIG lots from the same manufacturer. Furthermore, it was found that the effect of IVIG using one of the assay methods may not reliably predict activity obtained using the other assays. These data document the inability to predict functional activity against a specific pathogen such as GBS on the part of a lot of IVIG chosen at random. In view of these findings and of the limited data evaluating clinical efficacy, IVIG cannot be recommended at this time for use in the therapy of infectious diseases such as neonatal sepsis.

Animals↗

A polyclonal human IgG preparation hyperimmune for type III, group B Streptococcus: in vitro opsonophagocytic activity and efficacy in experimental models.

Neonates at risk for disease due to type III, group B Streptococcus (III-GBS) are those born with low serum levels of transplacentally derived, specific III-GBS antibody. Specific antibody is also required in vitro for opsonophagocytosis of III-GBS. Commercially available human immune serum globulins contain only moderate levels of III-GBS antibody. In the present study, IgG that was isolated from the serum of a human volunteer after vaccination with III-GBS polysaccharide contained very high levels of III-GBS antibody. Small amounts of this hyperimmune preparation added in vitro significantly increased the opsonophagocytosis of III-GBS in neonatal sera in the presence of polymorphonuclear leukocytes. Furthermore, small volumes of the preparation were protective in mouse and neonatal rat models of III-GBS disease. The administration of such hyperimmune human IgG preparations should be considered for preventing or treating III-GBS disease in infants.

Animals↗