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Biomedical subjects

D A Goldmann

Publications and source records attributed to D A Goldmann.

At least 73 records · Page 4Linked to original sources
PubMed1991

Protection against endocarditis due to Staphylococcus epidermidis by immunization with capsular polysaccharide/adhesin.

BACKGROUND: Staphylococcus epidermidis is the principal pathogen in prosthetic valve endocarditis. The capsular polysaccharide adhesin (PS/A) has been shown to mediate attachment of bacteria to medical devices. In this study, we investigated the efficacy of active and passive immunization against PS/A in preventing S. epidermidis endocarditis in a rabbit model. METHODS AND RESULTS: Aortic valve vegetations were produced by inserting a Teflon catheter into the left ventricle through the right carotid artery. Bacteremia and endocarditis were then established by implanting in the left jugular vein a catheter that was attached to an osmotic pump and contaminated with S. epidermidis strain RP62A. During a 3-week study period, of 64 blood cultures taken every second or third day from six nonimmune rabbits, 54 (84%) yielded strain RP62A. In rabbits actively immunized with PS/A, eight of 60 blood cultures (13%) were positive (odds ratio 5.0, 95% CI, 2.0-12.3, p = 0.005). At death, all six nonimmune rabbits had infected vegetations that yielded 10(6)-10(11) colony-forming units (cfu)/g of vegetation, whereas only one PS/A-immunized rabbit had an infected vegetation. Immunization protocols designed to elicit antibody to teichoic acid but not to PS/A afforded no protection against bacteremia or endocarditis. Infusion of monoclonal antibody to PS/A through a catheter in the right jugular vein provided a level of protection against both bacteremia and endocarditis comparable to that produced by active immunization. In vitro, antibody against PS/A was opsonic for S. epidermidis. CONCLUSIONS: Immunoprophylaxis targeted at staphylococcal PS/A is a promising new approach to the prevention of prosthetic valve endocarditis.

Animals↗
PubMed1990

Association of intravenous lipid emulsion and coagulase-negative staphylococcal bacteremia in neonatal intensive care units.

BACKGROUND AND METHODS: Coagulase-negative staphylococci are now the chief cause of bacteremia in neonatal intensive care units. To investigate potential risk factors for this nosocomial infection, we conducted a case--control study among 882 infants treated in two neonatal intensive care units during 1982. RESULTS: The 38 case patients and 76 controls were similar with respect to 27 indicators of the severity of the underlying illness. In addition, of the 20 potential risk factors for bacteremia that we investigated, only 2 met conventional criteria for causality. Infants with coagulase-negative staphylococcal bacteremia were 5.8 times as likely as controls (95 percent confidence interval, 4.1 to 8.3) to have received intravenous lipid emulsion before the onset of bacteremia. Because the use of lipids was common, 56.6 percent of all of the cases of nosocomial bacteremia could be attributed to lipid administration. Infants with bacteremia were also 3.5 times as likely as controls (95 percent confidence interval, 1.4 to 8.3) to have had a percutaneously inserted central venous catheter (attributable risk, 14.9 percent). The induction time for bacteremia after lipid administration, usually through peripheral catheters, was often less than one day. In contrast, the average induction period for nosocomial bacteremia associated with the use of central catheters, which were rarely used for lipid administration, was at least 5.5 days. Similar analyses of data on an additional 31 neonates treated in 1988 confirmed the strong and apparently independent association of coagulase-negative staphylococcal bacteremia with the intravenous administration of lipids (adjusted odds ratio, 5.3; 95 percent confidence interval, 3.5 to 6.7). CONCLUSIONS: The risk of coagulase-negative staphylococcal bacteremia in infants in neonatal intensive care units can be attributed primarily to the intravenous administration of lipid emulsions. Since lipids are critical for the nutritional support of premature infants, further studies are needed to examine the pathogenesis and prevention of lipid-associated bacteremia.

Catheterization, Central Venous↗
PubMed1990

Extra hospital stay and antibiotic usage with nosocomial coagulase-negative staphylococcal bacteremia in two neonatal intensive care unit populations.

Coagulase-negative staphylococci were the leading cause of nosocomial bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and Children's Hospital, Boston, Mass, in 1982. To determine the consequences of these nosocomial bacteremias, a cohort study was conducted in which two comparison subjects were matched with each of 38 bacteremic infants by hospital, birth weight within 100 g, and nearest date of discharge. To adjust for duration of stay in the hospital, it was also required that both comparison subjects have survived and remained in the hospital for as long as the time until bacteremia occurred in the bacteremic infant. The average day of onset of bacteremia was the 20th hospital day. Despite having similar birth weights and comparable severity of underlying illness, bacteremic infants remained in the hospital for an average of 19.8 days longer than the nonbacteremic comparison subjects (77.3 vs 57.5 days). The bacteremic patients received antibiotics for an average of 11.2 more days than the nonbacteremic infants. Vancomycin hydrochloride was given to 20 (52.6%) of the bacteremic patients but only 4 (5.3%) of the comparison patients. All of the comparison subjects and 37 of the 38 infants with bacteremia survived. Thus, nosocomial bacteremia with coagulase-negative staphylococci is a late complication of hospitalization that occurs in infants who are already relatively long-term survivors. This bacteremia appears to be associated with substantially longer hospital stay and antibiotic therapy but little, if any, excess mortality.

Cross Infection↗
PubMed1990

Coagulase-negative staphylococci: interplay of epidemiology and bench research.

Coagulase-negative staphylococci (CNS) are major nosocomial pathogens in patients with prostheses and indwelling devices such as central venous catheters. For Staphylococcus epidermidis the unique association with foreign-body infections appears to be due in part to a capsular polysaccharide adhesin that mediates attachment to silicon elastomer and other biomedical materials. In addition, staphylococcal "slime" may promote persistent colonization of indwelling devices and protect staphylococci from clearance by host defense mechanisms. Given these research findings, it seemed reasonable to assume that nosocomial CNS bacteremia in neonatal intensive care units might be associated with the use of indwelling vascular lines, as had been suggested by other investigators. We found that CNS cause the majority of nosocomial bacteremias in our neonatal intensive care units and that low birth weight and length of stay are major independent risk factors for these infections. In addition, we confirmed the association of central venous lines with CNS bacteremia but were surprised to find that intravenous administration of lipid emulsion was an even greater risk factor. These observations have brought our work back to the laboratory, where a rabbit model of CNS catheter infection is being studied to explore the relationship between lipid emulsion and catheter colonization and bacteremia.

Birth Weight↗
PubMed1990

Enzymatically labelled nucleic acid (NA) probe assays for detection of Campylobacter spp. in human faecal specimens and in culture.

Seventy-two stock clinical isolates of C. jejuni were tested with the SNAP Culture Identification Test Kit (Molecular Biosystems, Inc., San Diego, CA), an enzyme labelled nucleic acid probe colony blot assay, and with the Campyslide (BBL Microbiology Systems, Cockeysville, MD), a latex agglutination test. The sensitivity and overall agreement of both the SNAP and Campyslide tests were 100% in comparison with standard culture and identification tests. In addition, 14 C. jejuni, two C. laridis, and one 'C. upsaliensis', and one C. hyointestinalis, all fresh isolates from acutely ill patients, were detected with both tests. Ninety-eight faecal specimens from acutely ill patients were tested within 48 h using the probe based SNAP Diagnostic Test Kit (Molecular Biosystems, Inc.). Results were compared with standard culture. The probe test detected 4/6 specimens positive by culture; sensitivity was 66%. However, the two culture positive specimens, undetected by the probe test, had pathogens present at levels well below the probe test sensitivity (10(5) CFU g-1 stool). Specificity of the probe test was 98% (90/92 negative specimens) compared to culture. The results of this study demonstrate the accuracy of enzyme labelled oligonucleotide probes in the identification of C. jejuni isolated on culture and suggest a potential role for such probes in the direct detection of campylobacter in clinical faecal specimens.

Campylobacter↗
PubMed1990

Microbial challenge of a blood cell separator outside-seal bowl system.

The ability to store platelets beyond 24 hours requires a functionally closed system. This study tested the ability of a cell separator bowl seal system to resist penetration of microbial contamination under normal running conditions and under extreme environmental stress. Three test organisms, Micrococcus luteus, Serratia marcescens, and Staphylococcus epidermidis, were applied directly to the bowl at the edge of the seal or aerosolized and passed through the centrifuge chamber while the cell separator was run through a simulated platelet collection. A sterile, bacteriologic nutrient medium was perfused through the tubing set, thus simulating the flow of blood fractions. Following the procedure, the medium was examined for microbial growth. The concentration of aerosolized bacteria ranged from 5.2 x 10(1) to 3.9 x 10(3) colony-forming units (CFU) per mL, and the concentration of bacteria applied to the edge of the seal ranged from 1.9 x 10(5) to 2.8 x 10(9) CFU per mL. The positive control, direct inoculation of S. marcescens into the circulating medium (50 CFU/500 mL), resulted in recovery of the identical organism after 24 hours' incubation. No contamination of the system was detected in 40 experiments with aerosolized bacteria or in 32 experiments in which bacteria were applied directly to the seal. This study demonstrates that this sealed-bowl system resists microbial contamination.

Aerosols↗
PubMed1990

Antibody to the capsular polysaccharide/adhesin protects rabbits against catheter-related bacteremia due to coagulase-negative staphylococci.

A rabbit model of catheter-related bacteremia was developed to study immunity to the capsular polysaccharide/adhesin (PS/A) of coagulase-negative staphylococci. Catheters colonized by coagulase-negative staphylococci were inserted into the right jugular vein and attached to a subcutaneous osmotic pump, and blood cultures were obtained over 14 days. Nonimmune rabbits were bacteremic for 6-8 days after infection, hypoglycemic, and hyperlipidemic and had strong immune responses to teichoic acid but not to PS/A. PS/A immunization, but not teichoic acid immunization, reduced the number of bacteremic days by approximately 60%, diminished the hypoglycemia and hyperlipidemia, and ablated the immune responses to teichoic acid. Passive infusion of PS/A-specific polyclonal and monoclonal antibodies using a separate, noninfected catheter-pump combination implanted in the left jugular protected against both bacteremia and hematogenous colonization of this contralateral catheter.

Animals↗
PubMed1990

Birth weight and length of stay as determinants of nosocomial coagulase-negative staphylococcal bacteremia in neonatal intensive care unit populations: potential for confounding.

Coagulase-negative staphylococci are the most common cause of bacteremia in the neonatal intensive care units of the Brigham and Women's Hospital and the Children's Hospital, Boston, Massachusetts. In 1982, nosocomial bacteremia with coagulase-negative staphylococci occurred in 45 of 882 (5.1%) infants admitted to these units who survived and remained in intensive care for more than 48 hours and were therefore at risk. The overall cumulative incidence (attack rate) of nosocomial bacteremia rose dramatically with decreasing birth weight. The smallest infants, those with birth weights of less than 750 g, experienced an overall risk of nosocomial bacteremia 44.5 times that of infants with birth weights of greater than 2,000 g. A large part of the excess risk for small babies was attributable to their longer hospitalizations. However, after adjustment for length of stay, the smallest infants still suffered a daily rate of bacteremia (incidence density) 5.3 times that of the largest, indicating a considerable residual effect of birth weight on the daily risk of nosocomial coagulase-negative staphylococcal bacteremia. The results were similar in the two nurseries. Thus, there is still a substantially increased intrinsic risk of nosocomial coagulase-negative staphylococcal bacteremia among infants with very low birth weights, even after adjustment for duration of hospitalization, and differences in birth weight can confound comparative studies.

Birth Weight↗
PubMed1990

Current issues in central venous catheter infection.

The majority of central venous line-associated infections are caused by organisms on the skin near the exit site gaining access to the intravascular segment of the catheter. A variety of strategies have been used in an effort to reduce catheter contamination, but one innovation--the semipermeable transparent dressing--may actually increase infection risk. On the other hand, new catheter materials and designs probably reduce the risk. There are only a limited number of well-designed studies of the increasingly popular totally implantable catheter system and the multilumen line, but it appears that the former is associated with a low rate of infection, while the latter may be more hazardous than the single-lumen line.

Bacterial Infections↗
PubMed1989

Nosocomial viral infections: recent developments and new strategies.

Surveillance studies generally have underestimated the importance of viruses in the pathogenesis of nosocomial respiratory tract infections. The development of rapid, sensitive and reliable diagnostic techniques has permitted documentation of viral respiratory pathogens and has led to increased understanding of the epidemiology of these organisms in the hospital. These advances are exemplified by studies of respiratory syncytial virus infections in hospitalized children. The pulmonary sequelae of RSV infection are particularly serious in neonates and in children with underlying cardiopulmonary disease or immunodeficiency. Virus is spread by direct hand contact with the secretions of infected patients or with contaminated objects in the patients' environment. Personnel may infect themselves by rubbing their eyes or nose with contaminated hands, thus becoming vectors in the transmission of RSV to patients under their care. Compliance with contact precautions, which requires the use of gloves and gown, dramatically reduces the incidence of nosocomial RSV infection. When children do become ill, ribavirin may ameliorate the disease. Immunological approaches to treatment and prevention are being examined.

Child↗
PubMed1989

Heterologous protection against invasive Escherichia coli K1 disease in newborn rats by maternal immunization with purified mannose-sensitive pili.

Heterologous protection against Escherichia coli K1 bacteremia with antibody to purified mannose-sensitive (MS) pili was demonstrated in a neonatal rat model. The serological relatedness of purified MS pili from 17 E. coli K1 clinical isolates was examined by an enzyme-linked immunosorbent assay. Five pilus serogroups were identified, with the pili in each group showing 50% or greater cross-reactivity with the typing serum of the group. The MS pili from 12 of 17 (70%) strains belonged to just two serogroups. Pregnant Sprague-Dawley rats (dams) were immunized with purified pili, and their newborns (pups) were challenged with heterologous E. coli. Bacteremia was significantly reduced when the pili used for immunization were from the same serogroup as the pili expressed by the challenge bacteria. Thus, immunization with C94 pili and challenge with E03 (71% cross-reactivity) or E04 (50% cross-reactivity) resulted in bacteremia rates of 12 of 17 (17%) versus 51 of 79 (65%) in controls and 0 of 75 (0%) versus 28 of 70 (40%) in controls, respectively (P less than 0.001 for each comparison). With lower cross-reactivity, less protection was observed (P less than 0.05 for 22 to 37% pilus serological relatedness). No protection was seen in pups suckled by dams immunized with MS pili having only 5% serological relatedness to the pili on the challenge strain.

Animals↗
PubMed1989

Prevention and management of neonatal infections.

The risk of nosocomial infection in full term neonates cared for in well-baby nurseries can be minimized if personnel adhere to fundamental infection control principles. Neonates who require intensive care face a much greater risk of infection, particularly if they have very low birthweights. Such babies have seriously impaired host defenses, require prolonged hospital stays, and are exposed to a variety of invasive diagnostic and therapeutic procedures. They are extremely vulnerable to a wide range of nosocomial pathogens, including bacteria, fungi, and viruses, many of which are frank opportunists. Although it may not be possible to prevent all, or even most of these infections, careful attention to barrier precautions, adequate staffing, sound NICU design, and prompt case identification and cohorting can reduce the risk substantially.

Bacterial Infections↗
PubMed1988

Group B streptococcal infections of the central nervous system in infants with myelomeningocele.

Three cases of group B streptococcal infection of the central nervous system (CNS) occurred among 147 neonates treated for myelomeningocele at The Children's Hospital in Boston from 1970 to 1985. This pathogen was responsible for one third of the nine CNS infections noted in these patients over the 15-year study period. All three children with group B streptococcal CNS infections subsequently required multiple CNS shunting procedures and prolonged hospitalizations. Two children suffered major neurological sequelae. In neonates with myelomeningocele, group B streptococci have direct access to the CNS, perhaps explaining the high incidence of serious meningitis and ventriculitis in this population. Antibiotic prophylaxis for early myelomeningocele repair should be adjusted accordingly.

Central Nervous System Diseases↗
PubMed1988

The bacterial flora of neonates in intensive care-monitoring and manipulation.

Unlike healthy babies, newborns hospitalized in the neonatal intensive care unit (NICU) are colonized with bacterial flora that reflects their exposure to pathogens in the NICU, not bacterial acquired from mother in the perinatal period. For example, nosocomial Gram-negative bacilli, such as klebsiella, enterobacter, and citrobacter but not Escherichia coli tend to colonize the gastrointestinal tract. Colonization with Gram-negative bacilli generally is a prerequisite for nosocomial infection with these pathogens, but surveillance cultures may not be a cost effective approach to predicting which babies will ultimately become ill. However, screening cultures to detect the emergence of antibiotic-resistant Gram-negative bacilli facilitate containment and guide empiric antibiotic therapy, and surveillance cultures are necessary to detect colonized babies when nosocomial Gram-negative bacilli become epidemic in the NICU. Such cultures are inexpensive and easy to perform if appropriate selective media are used. Surveillance cultures to detect coagulase-negative staphylococci, which numerous investigators claim are increasingly important NICU pathogens, are of little value since colonization is virtually universal in the first week of life. Documentation of colonization with group B streptococci or Staphylococcus aureus also cannot be justified on a routine basis. Screening for methicillin-resistant S. aureus, however, may be indicated since early detection of these strains can limit dissemination in the NICU. Research aimed at restoring colonization resistance with elements of normal bacterial flora or preventing colonization by nosocomial pathogens is in its infancy.

Bacteriological Techniques↗
PubMed1988

Isolation and characterization of a capsular polysaccharide adhesin from Staphylococcus epidermidis.

We isolated a polysaccharide adhesin from Staphylococcus epidermidis strain RP-62A. The adhesin was composed of a complex mix of monosaccharides (with galactose and glucosamine predominating), bound well to silastic catheter tubing, inhibited adherence of strain RP-62A to catheters, and elicited antibodies that both blocked adherence and stabilized an extracellular structure (visualized by transmission electron microscopy) that appeared to be a capsule. Two of three heterologous, highly adherent strains of coagulase-negative staphylococci also produced this adhesin, and their adherence to catheters was inhibited by both purified adhesin and antibody to adhesin. In contrast, the adherence of one highly adherent and two poorly adherent heterologous strains was unaffected by the RP-62A purified adhesin or antibody, a result suggesting the expression of alternate adhesins by these strains. We conclude that the capsular polysaccharide of some strains of coagulase-negative staphylococci is an important factor in adherence to catheter tubing.

Adhesins, Bacterial↗