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Biomedical subjects

L G Rubin

Publications and source records attributed to L G Rubin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Intravenous catheter-related infections.

Vascular catheter-related infection is an important cause of mortality and morbidity in hospitalized patients. The mean incidence of catheter-related bloodstream infection in hospitalized pediatric patients is 2.4 episodes per 1,000 days. Totally implantable central venous catheters may be associated with a lower risk of infection. Coagulase-negative staphylococci are the predominant cause and account for about one third of episodes of catheter-related bloodstream infection. The diagnosis of catheter-related bloodstream infection is often difficult because there are frequently no signs of inflammation around the catheter. Diagnosis depends on either a positive quantitative catheter culture yielding the same microorganism recovered from the bloodstream or differential quantitative blood cultures with significantly greater colony counts from blood drawn through the catheter than from blood drawn through a peripheral vein. Alternatively, probably catheter-related sepsis can be diagnosed when clinical sepsis is refractory to antimicrobial therapy but responds to catheter removal. Often these criteria are not met but catheter-related bloodstream infection is presumed because a common skin microorganism is isolated from the blood when clinical manifestations of bloodstream infection are present and there is no other apparent source of infection. Microorganisms causing catheter-related bloodstream infection gain access to the bloodstream predominantly from either the catheter insertion site or the catheter hub. Most catheter-related infections occurring shortly after catheter insertion probably gain access to the bloodstream by extraluminal migration along the catheter from the skin at the catheter insertion site. When catheters are in place for extended periods, especially greater than 30 days, the catheter hub probably plays a major role in microorganisms gaining access and then migrating endoluminally until reaching the bloodstream. Recently employed strategies for the prevention of catheter-related infections include topical antibiotics or antiseptics at the catheter insertion site, flush solutions containing vancomycin, and bonding antimicrobial agents to the catheter. Infection of peripheral and central venous catheters generally resolves after catheter removal. For tunneled silicone catheters, most episodes of catheter-related infection can be initially managed with antimicrobial therapy infused through the catheter without catheter removal. Staphylococcus aureus is generally more aggressive and associated with more complications than coagulase-negative staphylococci. Microorganisms that usually require catheter removal include Candida and Bacillus species. Adjunctive treatments of catheter infections include the use of urokinase. Catheter-related infection remains an important complication of vascular access. Novel prevention and treatment strategies are currently being investigated. In the near future bonding of antibiotics or other agents to catheters may become routine.(ABSTRACT TRUNCATED AT 400 WORDS)

Bacteremia↗
PubMed1993

A prospective study of the catheter hub as the portal of entry for microorganisms causing catheter-related sepsis in neonates.

The hypothesis that catheter-related sepsis (CRS) may be preceded by contamination of the catheter hub was tested in neonates with central venous catheters. Cultures of the catheter hub were obtained three times per week. One hundred thirteen catheters were placed in 88 patients. Of 35 episodes of sepsis, 28 were catheter-related, for a catheter sepsis rate of 1.03/100 catheter-days. CRS occurred in 26 (23%) of 113 catheters. In 10 of 28 episodes, the infecting microorganism was cultured from the hub before its culture from blood obtained at the time of clinical sepsis. In an additional 5 cases, a culture of the catheter hub at the time of clinical sepsis yielded the same isolate as the blood culture. Thus, 54% of episodes of CRS were preceded by or coincided with contamination of the hub. The catheter hub may be a major portal of entry for microorganisms causing sepsis in a neonatal intensive care unit.

Bacteremia↗
PubMed1993

Role of lipooligosaccharide in virulence of the Brazilian purpuric fever clone of Haemophilus influenzae biogroup aegyptius for infant rats.

Clonally related strains of Haemophilus influenzae biogroup aegyptius have recently been associated with Brazilian purpuric fever (BPF), a fulminant, systemic disease in children. Using an infant rat bacteremia model for BPF, we found that a rat blood-passaged BPF isolate of H. influenzae biogroup aegyptius was more virulent than the original strain was. When compared with the original strain, the animal-passaged variant was found to display an altered lipooligosaccharide (LOS) phenotype and to lack pili. To examine the role of LOS phenotype and pili in virulence, we isolated isogenic variants differing in LOS phenotype or expression of pili. The virulence of variants was compared by examining the results of blood cultures obtained 24 h after intraperitoneal inoculation with 10(5) CFU. Our results indicate that the LOS phenotype is a critical determinant of BPF clone virulence for infant rats. To a lesser extent, the absence of piliation and an undefined additional factor(s) contribute to virulence.

Animals↗
PubMed1993

Use of disinfectants to reduce microbial contamination of hubs of vascular catheters.

The vascular catheter hub is a potential portal of entry for microorganisms that cause catheter-related sepsis. Thus, a reduction in catheter hub contamination might reduce the incidence of catheter-related sepsis. To develop a regimen suitable for reducing microbial contamination of the catheter hub, we experimentally contaminated catheter hubs and assessed the efficacies of disinfectant solutions. Catheter hubs were incubated overnight with suspensions of Staphylococcus epidermidis, Pseudomonas aeruginosa, or Candida parapsilosis. After removal of unattached microorganisms, the catheter hubs were swabbed by rotating cotton swabs dipped in 1% chlorhexidine, 1% chlorhexidine in 70% ethanol, 70% ethanol, 97% ethanol, or normal saline. Posttreatment swabs of the catheter hub were obtained and cultured quantitatively. The cleaning regimens containing ethanol were the most effective. Seventy percent ethanol was more effective than chlorhexidine and is likely to be the safest treatment. We conclude that cleaning of the catheter hub with disinfectant can dramatically reduce microbial contamination.

Catheterization, Peripheral↗
PubMed1993

Positive serology for Lyme borreliosis in patients with juvenile rheumatoid arthritis in a Lyme borreliosis endemic area: analysis by immunoblot.

Juvenile rheumatoid arthritis (JRA) and the arthritis of Lyme borreliosis in children can mimic each other. As false positive reactions are frequent in ELISA for Lyme borreliosis, they cannot be used reliably to make the distinction. Ninety-nine children diagnosed as having JRA at a children's hospital in an endemic area were evaluated by ELISA and immunoblot for antibodies to Borrelia burgdorferi. Sera from 9% were positive by ELISA, 5 of which showed bands on immunoblot. None met criteria for positive immunoblot. The antigenic basis of false positive ELISA was most frequently a reactivity to both 21 and 41 kDa. Analysis by immunoblot can help to definitively exclude Lyme borreliosis in children presenting with JRA in an endemic area.

Adolescent↗
PubMed1992

Immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease.

OBJECTIVE: To determine the safety and immunogenicity of Haemophilus influenzae type b conjugate vaccine in children with sickle cell disease. RESEARCH DESIGN: Prospective, nonrandomized, nonblinded study. SETTING: Hospital-based, comprehensive sickle cell center. PATIENTS: Children with sickle cell disease aged 18 months to 18 years who were previously unvaccinated or had an inadequate or waning response to H influenzae type b polysaccharide vaccine. SELECTION PROCEDURES: Consecutive eligible patients. INTERVENTIONS: Vaccination and observation for adverse effects. Blood samples were taken before and 1 to 2 and 6 months after vaccination to measure anticapsular antibody levels. MEASUREMENTS AND RESULTS: Vaccination was well tolerated. One hundred percent and 96% of the 31 immunized children had postvaccination anticapsular antibody concentrations of greater than 0.15 and 1.0 mg/L, respectively. Six months after vaccination, 100% and 89% of children had these antibody concentrations. CONCLUSIONS: H influenzae type b conjugate vaccines are safe and highly immunogenic in children with sickle cell disease. It is likely that these vaccines will be protective against invasive H influenzae type b disease.

Adolescent↗
PubMed1992

Vancomycin-resistant Enterococcus faecium in hospitalized children.

OBJECTIVE: Determine the epidemiology and risk factors for colonization with vancomycin-resistant Enterococcus faecium. DESIGN: Survey; case-control study. SETTING: Children's hospital. PATIENTS: Pediatric oncology patients. INTERVENTION: Contact isolation, restriction of vancomycin prescribing. RESULTS: There was a high prevalence of colonization with vancomycin-resistant enterococci among pediatric oncology patients. The length of hospitalization and the administration of vancomycin and other intravenous antibiotics was associated with colonization. Prevention of colonization was associated with restriction of vancomycin use and contact isolation. CONCLUSIONS: Vancomycin use may predispose to colonization with vancomycin-resistant E faecium. Vancomycin-resistant E faecium may be nosocomially spread. Contact isolation and restriction of vancomycin use may prevent spread of vancomycin-resistant E faecium.

Bacterial Typing Techniques↗
PubMed1992

Ocular manifestations of Mycoplasma pneumoniae infection.

Ocular manifestations of Mycoplasma pneumoniae infection, other than conjunctivitis, are uncommon. Optic disk swelling, optic nerve atrophy, retinal exudates and hemorrhages, and cranial nerve palsies have been infrequently reported. We describe a 15-year-old patient who developed bilateral optic disk edema and iritis during an acute infection with M. pneumoniae and review the world literature on findings associated with ocular manifestations of infection with this pathogen. Although our patient experienced complete resolution of iritis and optic disk edema after 6 weeks, several patients described in the literature have experienced permanent sequelae as a result of optic neuropathy.

Adolescent↗
PubMed1992

Antibodies to lipooligosaccharide of a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius lack bactericidal and protective activity.

The immunological basis for protection against Brazilian purpuric fever (BPF), a fulminant infection of young children associated with bacteremia with Haemophilus influenzae biogroup aegyptius, is unknown. Candidate antigens to which protective antibodies may be directed include cell surface proteins and lipooligosaccharide (LOS). We studied the activity of antisera to LOS purified from a BPF H. influenzae biogroup aegyptius isolate. Anti-LOS antisera contained anti-LOS antibody by enzyme immunoassay and immunoblot and no detectable anti-outer membrane protein antibodies by immunoblot. Anti-LOS antisera had minimal bactericidal activity and were not protective against the homologous strain in an infant rat model of bacteremia. Antiserum to whole bacterial cells had a titer of anti-LOS antibody similar to that of anti-LOS antisera and was bactericidal and protective. Removal of anti-LOS antibodies from anti-whole cell antiserum by affinity chromatography did not result in a loss of bactericidal activity. Serum from a normal adult contained anti-LOS antibodies and had bactericidal activity. However, anti-LOS antibodies purified from this serum did not have detectable bactericidal activity. These studies suggest that anti-LOS antibodies produced in rats are not bactericidal and do not contribute to protection against experimental bacteremia with BPF strains of H. influenzae biogroup aegyptius.

Animals↗
PubMed1991

Virulence of non-beta-lactamase-mediated ampicillin-resistant Haemophilus influenzae.

We questioned whether strains of ampicillin-resistant, non-beta-lactamase-producing (AmpR NBLP) Haemophilus influenzae with lower affinity penicillin-binding proteins (PBPs) might have altered virulence. The virulence of resistant transformant strains and the susceptible recipient was compared using infant rats. Following intraperitoneal inoculation, there was a significantly lower mortality rate and incidence and magnitude of bacteremia with two of three transformants compared to the recipient strain. Reduced virulence was not associated with greater bactericidal activity of serum or human neutrophils or faster clearance of the transformant following intravenous injection. Heated rat or human plasma supported exponential growth of the recipient, but not the transformant, suggesting deficient in vivo multiplication. We conclude that H. influenzae with altered PBPs are less virulent in an infant rat model which may be related to differences in in vivo growth.

Ampicillin Resistance↗
PubMed1991

Antibody to a 145-kilodalton outer membrane protein has bactericidal activity and protective activity against experimental bacteremia caused by a Brazilian purpuric fever isolate of Haemophilus influenzae biogroup aegyptius. The Brazilian Purpuric Fever Study Group.

The immunologic basis for protection against Brazilian purpuric fever, a septicemic infection associated with Haemophilus influenzae biogroup aegyptius bacteremia, is unknown. Passive immunization of infant rats with antiserum to whole bacterial cells of the homologous strain protects them from experimental bacteremia following bacterial challenge. In immunoblotting, antibody to a 145-kDa protein (P145) was present in protective antisera but not in nonprotective antisera. As judged by analysis of the antibodies eluted from whole bacterial cells and the agglutination of bacteria by antisera to P145, this protein is surface exposed. We prepared monospecific rat antisera to this protein by three methods: (i) immunization with whole bacterial cells and absorption with a Brazilian purpuric fever strain not expressing P145, (ii) immunization with gel-purified P145, and (iii) immunization with a P145-expressing transformant of a laboratory H. influenzae strain expressing this protein and absorption of the antiserum with the laboratory H. influenzae strain. These antisera had low antilipooligosaccharide antibody titers, were reactive only with P145, and had bactericidal activity in vitro. Following passive immunization, these antisera partially protected infant rats from bacteremia resulting from intraperitoneal challenge with bacteria. As assessed by immunoblotting, pooled adult human sera contained antibodies reactive with P145. Antibody to P145 may contribute to protection against Brazilian purpuric fever.

Animals↗
PubMed1990

Cefuroxime treatment failure of nontypable Haemophilus influenzae meningitis associated with alteration of penicillin-binding proteins.

A 10-year-old boy presented with nuchal rigidity and cerebrospinal fluid (CSF) leukocytosis initially and again on day 6 of intravenous cefuroxime therapy (200 mg/kg/day). Both CSF specimens yielded nontypable beta-lactamase-negative Haemophilus influenzae that were susceptible by disk tests but relatively resistant to cefuroxime (MIC, 8- to 16-fold greater than that of control isolates). To define the mechanism of resistance, the cefuroxime resistance marker was transformed to a susceptible H. influenzae recipient; inactivation and permeability of beta-lactam substrate were tested and the penicillin-binding protein (PBP) profiles were examined. Inactivation of beta-lactam substrate was not detected and reduced permeability was not found. However, reduced beta-lactam binding to PBPs 4 and 5 was observed; 18- to 27-fold more penicillin and 2.5-to 4-fold more cefuroxime was required to saturate or block 50% of the binding sites of these PBPs, respectively. Thus, reduced affinity of PBPs 4 and 5 for beta-lactam substrate appears to be the mechanism of cefuroxime resistance in this strain. The reduced affinity of these targets appears to have contributed to the bacteriologic and clinical failure in this patient.

Ampicillin↗
PubMed1989

The molecular basis of pathogenicity in Haemophilus influenzae: comparative virulence of genetically-related capsular transformants and correlation with changes at the capsulation locus cap.

Serotype b strains of Haemophilus influenzae are strikingly more highly associated with episodes of invasive, life-threatening infection in young children than are strains of other serotypes, but the role that the capsule itself plays in determining this virulence has not been dissected away from that of possibly linked virulence determinants such as lipopolysaccharide (LPS). Using DNA from clinical isolates of all six serotypes (a-f) and a genetically-defined capsule-deficient recipient strain Rb-: 02, we constructed a series of capsular transformants otherwise identical with respect to outer-membrane protein and LPS subtype, biotype, and electrotype. Cloned DNA was also used to create type a and b transformants isogenic outside the capsulation locus to provide the most rigorous test to determine whether capsule alone modulates pathogenicity. Capsular transformants showed the same spectrum of virulence in an infant rat bacteremia/meningitis assay as wild-type strains, thus implicating the capsule polysaccharide as an independent determinant of virulence. Experiments in intact and splenectomised rats identified a critical role for type b capsule in enabling organisms to evade splenic clearance.

Animals↗