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Biomedical subjects

J Huebner

Publications and source records attributed to J Huebner.

At least 19 recordsLinked to original sources

Distribution of four capsular serotypes of Enterococcus faecalis among clinical isolates from different geographical origins and infection sites.

BACKGROUND: Enterococci possess capsular polysaccharide antigens that are the targets of opsonic antibodies. These antibodies are potential candidates for development as immunotherapy. MATERIAL AND METHODS: The present study analyzes the distribution of four capsular serotypes within a collection of 157 isolates of Enterococcus faecalis from four countries with different sites of clinical infection. RESULTS: By using a capsular polysaccharide-specific ELISA, 42% of the isolates were grouped into one of four serogroups, and another 9% showed cross-reactivity between two serotype-specific sera. Heterogeneity of serotype distribution by both geographical origin and infection site was observed. CONCLUSION: Half of the strain collection could be typed with four serotype-specific sera. No serotype from a given country or infection site clearly predominated.

Bacterial Capsules↗

Analysis of the specific immune response against capsular polysaccharides of two patients with systemic enterococcal infections.

Systemic enterococcal infections often lead to life-threatening disease. By analyzing the immune response of two patients with systemic enterococcal infections against enterococcal polysaccharide antigens, we found that both patients had antibodies against all four of the capsular serotypes identified to date. Antibody concentrations against the causative capsular serotype were in the same range as antibodies against the other three capsular protoserotypes. Interestingly, we noted a difference between the two patients with respect to opsonic activity in the killing assay: one patient showed better killing of all four capsular prototypes than the other. However, killing against the infecting serotype was not increased in comparison to killing of the other serotypes in the two patients. This finding supports previously published data that most healthy humans possess preexisting, naturally acquired, anti-enterococcal antibodies. We conclude, therefore, that systemic infection with enterococci does not lead to higher antibody concentrations or better opsonic killing against the causative capsular serotype.

Antibodies, Bacterial↗

In vitro assessment of the host response against Enterococcus faecalis used in probiotic preparations.

Along with other lactic acid bacteria, enterococci are used in food products and as health promoting agents. The safety of these products must be ensured, because they contain potentially pathogenic microorganisms. Here we present an in vitro opsonophagocytic assay that closely mimics the protective human immune response to Enterococcus faecalis and Enterococcus faecium. A collection of closely related E. faecalis isolates used as probiotics showed different susceptibilities to opsonic killing, suggesting that some of these isolates possess a capsule while other do not. This information may be helpful in assessing the safety of a given bacterial isolate used and could detect likely enterococcal candidates for probiotic preparations.

Bacterial Capsules↗

Implant infections due to enterococci: role of capsular polysaccharides and biofilm.

Enterococci are natural inhabitants of the gastrointestinal tract and of the female genital tract of humans and many animals. In recent years, enterococci have been increasingly recognized as important human pathogens causing infections associated with medical devices. Their resistance to most antimicrobial agents and their ability to form biofilm has contributed to the increasing incidence of nosocomial enterococcal infections. Enterococci possess a capsular polysaccharide composed of a glycerol-teichoic acid-like molecule consisting of repeating units of 6-alfa-D-glucose-1-2-glycerol-3-PO4 , substituted on carbon 2 with a alfa-2,1-linked molecule of glucose. Using both immunologic and genetic data E. faecalis can be assigned to specific serotypes based on capsular polysaccharides. Clinical examples of foreign-body infections due to enterococci are described, comprising infections of artificial joints, implanted intravascular catheters, artificial hearts and artificial valves, stents, liquor shunt devices, and intraocular infections. Methods to prevent and/or treat enterococcal infections are presented.

Anti-Bacterial Agents↗

Control of multiply resistant cocci: do international comparisons help?

Antibiotic resistance has become a worldwide problem. However, the reasons for the uneven geographic distribution of antibiotic-resistant microorganisms are not fully understood. For instance, there are striking differences in the epidemiology of multiresistant gram-positive cocci between the USA and Germany. According to recent reports, the prevalence of high-level penicillin-resistant pneumococci (PRP), meticillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) in clinically relevant isolates of hospitalised patients in the USA and Germany are: PRP, 14% versus less than 1%; MRSA, 36% versus 15%; and VRE, 15% versus 1%. These disparities may be explained by several determinants: (1) diagnostic practice and laboratory recognition (all three pathogens); (2) clonal differences and pathogen transmissibility (VRE); (3) antibiotic prescribing practices (all three pathogens); (4) population characteristics, including extensive daycare exposure in the USA (PRP); (5) cultural factors (all three pathogens); (6) factors related to the health-care and legal system (all three pathogens); and (7) infection-control practices (MRSA and VRE). Understanding these determinants is important for preventing further spread of multiresistant cocci within the USA. A rational approach to national surveillance is urgently needed in Germany to preserve the favourable situation and decrease MRSA transmission. Finally, we suggest that a macro-level perspective on antibiotic resistance can broaden the understanding of this worldwide calamity, and help prevent further dissemination of multiply resistant microorganisms.

Anti-Bacterial Agents↗

The influence of geopolitical change on the well-being of a population: the Berlin Wall.

OBJECTIVES: Social cohesion is recognized as a fundamental condition for healthy populations, but social cohesion itself arises from political unity. The history of the Berlin Wall provides a unique opportunity to examine the effects of partition on social cohesion and, by inference, on health. METHODS: This ethnographic study consisted of examination of the territory formerly occupied by the Wall, formal and informal interviews with Berlin residents, and collection of cultural documents related to the Wall. Transcripts, field notes, and documents were examined by means of a keyword-in-context analysis. RESULTS: The separation of Berlin into 2 parts was a traumatic experience for the city's residents. After partition, East and West Germany had divergent social, cultural, and political experiences and gradually grew apart. CONCLUSIONS: The demolition of the Wall--the symbol and the instrument of partition--makes possible but does not ensure the reintegration of 2 populations that were separated for 40 years. The evolution of a new common culture might be accelerated by active attempts at cultural and social exchange.

Berlin↗

Prophylactic and therapeutic efficacy of antibodies to a capsular polysaccharide shared among vancomycin-sensitive and -resistant enterococci.

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-microg 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.

Animals↗

Structure of an antigenic teichoic acid shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium.

A shared antigenic teichoic acid, previously found to be a surface capsule-like polysaccharide, was isolated from clinical isolates of Enterococcus faecalis and vancomycin-resistant E. faecium. It was composed of glucose, glycerol, and phosphate as determined by chemical and GC-MS analysis. The repeating-unit structure was elucidated by a series of 1H, 13C, and 31P NMR spectroscopy to be the following: [formula: see text]

Antigens, Bacterial↗

Isolation and chemical characterization of a capsular polysaccharide antigen shared by clinical isolates of Enterococcus faecalis and vancomycin-resistant Enterococcus faecium.

Enterococci are a common cause of serious infections, especially in newborns, severely immunocompromised patients, and patients requiring intensive care. To characterize enterococcal surface antigens that are targets of opsonic antibodies, rabbits were immunized with various gentamicin-killed Enterococcus faecalis strains, and immune sera were tested in an opsonophagocytic assay against a selection of clinical isolates. Serum raised against one strain killed the homologous strain (12030) at a dilution of 1:5,120 and mediated opsonic killing of 33% of all strains tested. In addition, this serum killed two (28%) of seven vancomycin-resistant Enterococcus faecium strains. Adsorption of sera with the homologous strain eliminated killing activity. The adsorbing antigens were resistant to treatment with proteinase K and to boiling for 1 h, but were susceptible to treatment with sodium periodate, indicating that the antigen inducing opsonic activity is a polysaccharide. Antibodies in immune rabbit sera reacted with a capsule-like structure visualized by electron microscopy both on the homologous E. faecalis strain and on a vancomycin-resistant E. faecium strain. The capsular polysaccharides from E. faecalis 12030 and E. faecium 838970 were purified, and chemical and structural analyses indicated they were identical glycerol teichoic acid-like molecules with a carbohydrate backbone structure of 6-alpha-D-glucose-1-2 glycerol-3-PO4 with substitution on carbon 2 of the glucose with an alpha-2-1-D-glucose residue. The purified antigen adsorbed opsonic killing activity from immune rabbit sera and elicited high titers of antibodies (when used to immunize rabbits) that both mediated opsonic killing of bacteria and bound to a capsule-like structure visualized by electron microscopy. These results indicate that approximately one-third of a sample of 15 E. faecalis strains and 7 vancomycin-resistant E. faecium strains possess shared capsular polysaccharides that are targets of opsonophagocytic antibodies and therefore are potential vaccine candidates.

Animals↗

Coagulase-negative staphylococci: role as pathogens.

Coagulase-negative staphylococci have long been regarded as apathogenic but their important role as pathogens and their increasing incidence have been recognized and studied in recent years. Although specific virulence factors are not as clearly established as they are in Staphylococcus aureus, it seems clear that factors such as bacterial polysaccharide components are involved in attachment and/or persistence of bacteria on foreign materials. Coagulase-negative staphylococci are by far the most common cause of bacteremia related to indwelling devices. Most of these infections are hospital-acquired, and studies over the past several years suggest that they are often caused by strains that are transmitted among hospitalized patients. Other important infections due to coagulase-negative staphylococci include central nervous system shunt infections, native or prosthetic valve endocarditis, urinary tract infections, and endophthalmitis. Intravenous treatment of systemic infections is usually required because coagulase-negative staphylococci have become increasingly resistant to multiple antibiotics.

Anti-Bacterial Agents↗

What physicians can learn from consumers of dietary supplements.

BACKGROUND: Many Americans consume dietary supplements, including vitamins, minerals, herbs, and amino acids. Government regulation of dietary supplements is limited, and patients typically do not consult with their physicians regarding the use of supplements. METHODS: We conducted a qualitative study to describe patients' decisions about the use of dietary supplements and the communication they have with their physicians about such use. Four focus groups of customers from 3 local suburban health food stores were interviewed. RESULTS: The customers in the health food stores we investigated were motivated to pursue wellness and wanted to take responsibility for their health. They would welcome a partnership with their physicians, but generally believed that physicians are closed-minded and have little knowledge about dietary supplements. These consumers determined the effectiveness of dietary supplements through personal study and subjective experimentation. CONCLUSIONS: The health food store customers in our study were self-informed consumers who did not consult their physicians about their use of dietary supplements, because they did not believe that physicians were knowledgeable about or interested in supplements. An open-minded patient-centered approach would help physicians provide better care for patients who use dietary supplements.

Adolescent↗

Effect of therapeutic concentrations of nitric oxide on bacterial growth in vitro.

OBJECTIVES: Besides its vasodilative actions, nitric oxide (NO) is also involved in host defense on a cellular level. We studied the antimicrobial properties of NO in concentrations used with inhaled NO therapy for the treatment of pulmonary hypertension in neonates. DESIGN: In vitro study of bacterial growth of five species, with and without NO exposure. SETTING: Level IV neonatal intensive care unit at a university children's hospital. SUBJECTS: In vitro bacterial cultures. INTERVENTIONS: We tested ten different strains of five bacterial species (Staphylococcus aureus, Staphylococcus epidermidis, group B streptococcus [GBS/Streptococcus agalactiae], Escherichia coli, and Pseudomonas aeruginosa), derived from the tracheal isolates of ventilated premature and term infants. Cultures were exposed to three different concentrations of NO (40, 80, and 120 parts per million [ppm]) and bacterial growth was compared with the same strains incubated in ambient air for 24 hrs. After incubation (with or without NO), colony-forming units were counted. MEASUREMENTS AND MAIN RESULTS: Bacterial growth of S. aureus, E. coli, and P. aeruginosa was not reduced with the NO concentrations applied. The number of colony-forming units of S. aureus increased at 80 ppm of NO. Growth of S. epidermidis and GBS was significantly affected at 120 ppm, resulting in decreased numbers of colony-forming units as compared with controls exposed to ambient air. CONCLUSIONS: We conclude that NO has a selective bacteriostatic effect on some of those bacteria most commonly cultured in tracheal specimens of premature infants and neonates. This effect appears to be dose-dependent and occurs in the upper range of dosages used with inhaled NO therapy. However, in the range of dosages applied in ongoing controlled trials of inhaled NO in neonates and premature infants (1 to 80 ppm), a bacteriostatic effect of NO is not to be expected.

Administration, Inhalation↗

Endemic nosocomial transmission of Staphylococcus epidermidis bacteremia isolates in a neonatal intensive care unit over 10 years.

To assess long-term nosocomial transmission, trends in antibiotic resistance, and expression of potential virulence factors, 86 randomly selected Staphylococcus epidermidis bloodstream isolates obtained from 80 patients in a neonatal intensive care unit (NICU) over a 10-year period were studied. Pulsed-field gel electrophoresis (PFGE) analysis of SmaI-digested whole chromosomal DNA revealed distinctive banding patterns that persisted in the NICU over long periods. Pattern A included 22 isolates (26%) obtained during 1983-1990, and pattern B included 24 isolates (28%) from 1983 to 1991. All 10 isolates examined in 1984 fell into one of these two patterns. Isolates with either pattern expressed polysaccharide/adhesin (PSA) and slime; 90% and 87% were resistant to oxacillin and gentamicin, respectively, with no trends over time. These findings suggest that distinct clones of S. epidermidis can become endemic in NICUs over periods as long as a decade and that nosocomial transmission plays an important role in neonatal S. epidermidis bacteremia.

Bacteremia↗

Exogenous or endogenous reservoirs of nosocomial Pseudomonas aeruginosa and Staphylococcus aureus infections in a surgical intensive care unit.

OBJECTIVE: A 4 month prospective study was performed to assess the incidence and routes of endogenous or exogenous colonization and nosocomial infection caused by Staphylococcus aureus and Pseudomonas aeruginosa in surgical critically ill patients. DESIGN: A total of 4634 specimens were obtained. Patient's nasal, scalp, and rectal swabs as well as tracheal secretion (TS) were cultured every second day beginning on the day of admission. Nasal swabs and hand cultures of the personnel as well as cultures from gowns were also taken. All isolates of S. aureus were phage typed and 116 of these isolates were also plasmid typed. P. aeruginosa isolates were sero- and pyocin typed. Resistance patterns were determined in all isolates. SETTING: The study was carried out in the surgical intensive care unit (SICU) of an teaching hospital. PATIENTS: During the study period each patient (a total of 153 patients) admitted to the SICU entered the study. RESULTS: P. aeruginosa and S. aureus colonisation rate on admission were 5% and 36.5% respectively. Only 10 patients (6.5%) were colonized with P. aeruginosa during hospitalization, and only 7 patients (4.5%) acquired S. aureus in the surgical intensive care unit (SICU). The most common primary colonisation site of P. aeruginosa was the rectum, whereas S. aureus was predominantly found in nasal cultures. Horizontal transmission of S. aureus occurred in only 2 patients. CONCLUSION: The study suggests that colonisation with P. aeruginosa and S. aureus occurs from endogenous rather than from exogenous sources and that the endogenous acquisition of both bacteria play a more important role in development of nosocomial infections than the exogenous route of transmission.

Cross Infection↗

In vitro activity of vancomycin and teicoplanin against Staphylococcus aureus and Staphylococcus epidermidis colonizing catheters.

In a quantitative in vitro model the activity of vancomycin and teicoplanin in two concentrations (4 x MBC and 1 mg/l) against Staphylococcus aureus and a slime-producing Staphylococcus epidermidis strain colonizing the internal surface of polyurethane and silicone catheters was studied. In comparison with vancomycin, teicoplanin achieved a significantly greater reduction (p < 0.05) in the counts of Staphylococcus aureus and Staphylococcus epidermidis adhering to both polyurethane and silicone catheters.

Catheterization, Central Venous↗