Showing papers by "Donald A. Goldmann published in 2000"

Occurrence of nosocomial bloodstream infections in six neonatal intensive care units.

Abstract: Background.Nosocomial bloodstream infections (NBSIs) occur frequently in neonatal intensive care units (NICUs) and are associated with substantial morbidity and mortality. Little has been published regarding variation in NBSI among institutions.Objective.To determine NBSI incidence among six NICUs a

Transmission of viral respiratory infections in the home.

Abstract: Respiratory viruses in the home exploit multiple modes of transmission. RSV is transmitted primarily by contact with ill children and contaminated objects in the environment. Influenza appears to be spread mainly by airborne droplet nuclei. Despite many years of study, from the plains of Salisbury, to the hills of Virginia, to the collegiate environment of Madison, WI, the precise routes rhinovirus takes to inflict the misery of the common cold on a susceptible population remain controversial.

Prophylactic and Therapeutic Efficacy of Antibodies to a Capsular Polysaccharide Shared among Vancomycin-Sensitive and -Resistant Enterococci

Abstract: Enterococci are important nosocomial pathogens that are increasingly difficult to treat due to intrinsic and acquired resistance to antibiotics, including vancomycin. A recently described capsular polysaccharide (CP) isolated from Enterococcus faecalis 12030 was used to evaluate the potential efficacy of active or passive immunotherapy regimens as adjunctive treatments. Evaluation of protective efficacy was carried out in immunocompetent mice challenged intravenously (i.v.) with live enterococci. In nonimmune mice, i.v. inoculations resulted in high levels of bacteria in kidneys, spleens, and livers 5 days after challenge. Mice immunized with four 10-μg doses of CP antigen/mouse were protected against challenge with the homologous E. faecalis strain. High-titer opsonic immunoglobulin G was also induced by immunizing rabbits with the purified CP, and passive transfer of this antiserum to mice produced significantly lower bacterial counts in organs than did normal rabbit serum or sterile saline. Antibodies to the polysaccharide isolated from E. faecalis 12030 were protective against Enterococcus faecalis OG1RF and against two serologically related, vancomycin-resistant Enterococcus faecium clinical isolates. Antibodies to this CP antigen were also effective as a therapeutic reagent in mice when passive therapy was initiated 48 h after live bacterial challenge. These data indicate that CP antigens from enterococci are potential targets of protective antibodies and that these antibodies may be useful for prophylaxis and treatment of enterococcal infections.

Enhancement of Neonatal Innate Defense: Effects of Adding an N-Terminal Recombinant Fragment of Bactericidal/Permeability-Increasing Protein on Growth and Tumor Necrosis Factor-Inducing Activity of Gram-Negative Bacteria Tested in Neonatal Cord Blood Ex Vivo

Abstract: Innate defense against microbial infection requires the action of neutrophils, which have cytoplasmic granules replete with antibiotic proteins and peptides. Bactericidal/permeability-increasing protein (BPI) is found in the primary granules of adult neutrophils, has a high affinity for lipopolysaccharides (or "endotoxins"), and exerts selective cytotoxic, antiendotoxic, and opsonic activity against gram-negative bacteria. We have previously reported that neutrophils derived from newborn cord blood are deficient in BPI (O. Levy et al., Pediatrics 104:1327-1333, 1999). The relative deficiency in BPI of newborns raised the possibility that supplementing the levels of BPI in plasma might enhance newborn antibacterial defense. Here we determined the effects of addition of recombinant 21-kDa N-terminal BPI fragment (rBPI(21)) on the growth and tumor necrosis factor (TNF)-inducing activity of representative gram-negative clinical isolates. Bacteria were tested in citrated newborn cord blood or adult peripheral blood. Bacterial viability was assessed by plating assay, and TNF-alpha release was measured by enzyme-linked immunosorbent assay. Whereas adult blood limited the growth of all isolates except Klebsiella pneumoniae, cord blood also allowed logarithmic growth of Escherichia coli K1/r and Citrobacter koseri. Bacteria varied in their susceptibility to rBPI(21)'s bactericidal action: E. coli K1/r was relatively susceptible (50% inhibitory concentration [IC(50)], approximately 10 nM), C. koseri was intermediate (IC(50), approximately 1,000 nM), Klebsiella pneumoniae was resistant (IC(50), approximately 10,000 nM), and Enterobacter cloacae and Serratia marcescens were highly resistant (IC(50), >10,000 nM). All isolates were potent inducers of TNF-alpha activity in both adult and newborn cord blood. In contrast to its variable antibacterial activity, rBPI(21) consistently inhibited the TNF-inducing activity of all strains tested (IC(50), 1 to 1,000 nM). The antibacterial effects of rBPI(21) were additive with those of a combination of conventional antibiotics typically used to treat bacteremic newborns (ampicillin and gentamicin). Whereas ampicillin and gentamicin demonstrated little inhibition of bacterially induced TNF release, addition of rBPI(21) either alone or together with ampicillin and gentamicin profoundly inhibited release of this cytokine. Thus, supplementing newborn cord blood with rBPI(21) potently inhibited the TNF-inducing activity of a variety of gram-negative bacterial clinical pathogens and, in some cases, enhanced bactericidal activity. These results suggest that administration of rBPI(21) may be of clinical benefit to neonates suffering from gram-negative bacterial infection and/or endotoxemia.

Reducing medical error through systems improvement: the management of febrile infants.

Abstract: Worry about avoiding the disaster of overwhelming bacterial sepsis in a young febrile infant has cost many a pediatrician sleepless nights. Which infant is destined to become critically ill and which will recover in a few days from a trivial viral infection without treatment? Unable to predict reliably the course of febrile illnesses, pediatricians often select the option of treating many infants to benefit a few. Faced with the inefficiency and risks of universal treatment of febrile infants, several investigators have developed strategies to identify low-risk infants who could be safely observed without antibiotics.1–3 These approaches use various clinical and laboratory criteria that are applied prospectively to an eligible population of febrile infants. In research settings, the best of these protocols can reliably discriminate between high-risk infants who warrant inpatient admission and antibiotic therapy, and low-risk infants who can safely be managed conservatively with close outpatient observation. Can these evidence-based risk assessment protocols be applied successfully outside the research settings in which they were developed? A recent study by Baker and colleagues4 in Pediatrics suggests that such strategies should be pursued with caution. In particular, the study confirms the importance of error in medicine and the need to improve systems of care if we are to safely reduce cost and improve outcomes. The authors report the performance of the Philadelphia protocol in guiding the treatment of a consecutive sample of 422 febrile infants presenting to the emergency department of the Children's Hospital of Philadelphia. The study yielded 2 important, yet discordant, findings: 1. The Philadelphia protocol performed reliably in identifying as high-risk all infants with serious bacterial infection (SBI). 2. Overall 6.6% of infants were treated contrary to the clinical course dictated by the protocol, experiencing both overtreatment and undertreatment. Twenty-one (6.5%) of 321 high-risk infants were treated as low-risk …