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Biomedical subjects

D A Goldmann

Publications and source records attributed to D A Goldmann.

At least 37 records · Page 2Linked to original sources

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↗

Hospital infection prevention and control: a model for improving the quality of hospital care in low- and middle-income countries.

Continuous quality improvement (CQI) is a powerful methodology for improving clinical outcomes and patient satisfaction while reducing inefficiency and costs. However, most hospitals in low- and middle-income countries have little experience with CQI methods. Hospital infection prevention is an ideal model for nascent efforts to improve the quality of hospital care because of its proven efficacy in reducing the occurrence of infections that compromise patient outcomes and increase costs. This article describes the design and implementation of a demonstration project to reduce the incidence of surgical-site infections (SSIs) for hospitals with little experience with quality-improvement methods. The project has a high likelihood of producing measurable reductions in SSI rates and hospital costs related to inefficient use of perioperative antimicrobial prophylaxis. Moreover, participating staff will gain experience that can be applied to efforts to improve the quality of other aspects of hospital care.

Developing Countries↗

Intravenous lipid emulsions are the major determinant of coagulase-negative staphylococcal bacteremia in very low birth weight newborns.

BACKGROUND: Intravenous lipid emulsions and the i.v. catheters through which they were administered were the major risk factors for nosocomial coagulase-negative staphylococcal (CONS) bacteremia among newborns in our neonatal intensive care units a decade ago. However, medical practice is changing, and these and other interventions may have different effects in the current setting. OBJECTIVES: We determined the independent risk factors for CONS bacteremia in current very low birth weight newborns after adjusting for severity of underlying illness. METHODS: We surveyed 590 consecutively admitted newborns with birth weights < 1500 g hospitalized in 2 neonatal intensive care units and conducted a case-control study in a sample of 74 cases of CONS bacteremia and 74 pairs of matched controls. Adjusted relative odds of bacteremia were estimated for a number of attributes and therapeutic interventions in 2 time intervals before CONS bacteremia: any time before bacteremia and the week before bacteremia. RESULTS: Using conditional logistic regression to adjust for indicators of severity of illness, two procedures were independently associated with subsequent risk of CONS bacteremia at any time during hospitalization: i.v. lipids, odds ratio (OR) = 9.4 [95% confidence interval (CI) 1.2 to 74.2]; and any surgical or percutaneously placed central venous catheter, OR = 2.0 (95% CI 1.1 to 3.9). Considering only the week immediately preceding bacteremia, the independent risk factors were: mechanical ventilation, OR = 3.2 (95% CI 1.3 to 7.6); and short peripheral venous catheters, OR = 2.6 (95% CI 1.0 to 6.5). CONCLUSIONS: During the last decade exposure to i.v. lipids any time during hospitalization has become an even more important risk factor for CONS bacteremia (OR = 9.4). Of these bacteremias 85% are now attributable to lipid therapy. In contrast the relative importance of intravenous catheters as independent risk factors has declined. Mechanical ventilation in the week before bacteremia has emerged as a risk factor for bacteremia.

Bacteremia↗

The ica locus of Staphylococcus epidermidis encodes production of the capsular polysaccharide/adhesin.

Clinical isolates of coagulase-negative staphylococci often elaborate a biofilm involved in adherence to medical devices and resistance to host defenses. The biofilm contains the capsular polysaccharide/adhesin (PS/A), which mediates cell adherence to biomaterials, and another antigen, termed polysaccharide intercellular adhesin (PIA), which is thought to mediate bacterial accumulation into cellular aggregates. PIA is a polymer of beta-1, 6-linked N-acetyl glucosamine residues with a molecular mass of <30, 000 kDa. We found that recombinant Staphylococcus carnosus and Staphylococcus aureus carrying a plasmid with genes of the ica locus, which was reported to encode the biosynthetic proteins for production of PIA, were also able to synthesize PS/A. PS/A and a chemically and immunologically identical polysaccharide isolated from S. carnosus carrying the ica genes on plasmid pCN27 were found to be high-molecular-mass (>250,000 kDa), acid-stable polymers of beta-1,6-linked glucosamine substituted on the amino group primarily with succinate, although some preparations also contained acetate. Moreover, all recombinant staphylococcal strains with the ica genes had the biologic properties previously attributed to PS/A. ica-positive strains readily formed an in vitro biofilm on plastic, adhered 3- to 10-fold more to catheters during a 30-min assay compared with control strains carrying only the cloning vector, adsorbed out antibodies to PS/A from immune serum, and elaborated a capsule visualized by immunoelectron microscopy with antisera to PS/A. These properties were also seen with PS/A-producing strains of Staphylococcus epidermidis, but not with transposon mutants lacking PS/A. An antiserum raised to PIA contained high-titer antibody to PS/A that was readily adsorbed out by PS/A-positive strains of S. epidermidis and recombinant strains of staphylococci carrying the ica genes. We conclude that the ica locus encodes production of PS/A and that the properties of S. epidermidis associated with initial bacterial adherence, biofilm formation, and intercellular adhesion can be correlated with elaboration of PS/A.

Adhesins, Bacterial↗

Declining severity adjusted mortality: evidence of improving neonatal intensive care.

OBJECTIVES: Declines in neonatal mortality have been attributed to neonatal intensive care. An alternative to the "better care" hypothesis is the "better babies" hypothesis; ie, very low birth weight infants are delivered less ill and therefore have better survival. DESIGN: We ascertained outcomes of all live births <1500 g in two prospective inception cohorts. We estimated mortality risk from birth weight and illness severity on admission and measured therapeutic intensity. We calculated logistic regression models to estimate the changing odds of mortality between cohorts. PATIENTS AND SETTING: Two cohorts in the same two hospitals, 5 years apart (1989-1990 and 1994-1995) (total n = 739). RESULTS: Neonatal intensive care unit mortality declined from 17.1% to 9.5%, and total mortality declined from 31.6% to 18.4%. Cohort 2 had lower risk (higher birth weight, gestational age, and Apgar scores and lower admission illness severity for newborns >/=750 g). Risk-adjusted mortality declined (odds ratio, 0.52; confidence interval, 0.29-0. 96). One third of the decline was attributable to "better babies" and two thirds to "better care." Use of surfactant, mechanical ventilation, and pressors became more aggressive, but decreases in monitoring, procedures, and transfusions resulted in little change in therapeutic intensity. CONCLUSIONS: Mortality decreased nearly 50% for infants <1500 g in 5 years. One third of this decline is attributable to improved condition on admission that reflects improving obstetric and delivery room care. Two thirds of the decline is attributable to more effective newborn intensive care, which was associated with greater aggressiveness of respiratory and cardiovascular treatments. Attribution of improved birth weight specific mortality solely to neonatal intensive care may underestimate the contribution of high-risk obstetric care in providing "better babies."

Hospital Mortality↗

Control of nosocomial antimicrobial-resistant bacteria: a strategic priority for hospitals worldwide.

The rapid emergence and dissemination of antimicrobial-resistant microorganisms in hospitals worldwide is a problem of crisis dimensions. The root causes of this problem are multifactorial, but the core issues are clear. The emergence of antimicrobial resistance is highly correlated with selective pressure that results from inappropriate use of antimicrobial agents. Dissemination of resistant organisms is facilitated by person-to-person transmission due to inconsistent application of basic infection control practices by hospital personnel. While control strategies exist, the interventions are not likely to be successful unless hospital leaders assume the responsibility for control of antimicrobial resistance. Strategic goals for the control of resistant organisms should be formulated on the basis of multidisciplinary input from hospital personnel. Processes and outcomes relevant to these strategic goals should be measured, and the resultant data should be used to design, implement, and evaluate systematic measures to increase the appropriate use of antimicrobial agents and basic infection control practices. This approach is as relevant to hospitals in countries with limited resources as it is to in fully industrialized countries.

Algorithms↗

Strategies to Prevent and Control the Emergence and Spread of Antimicrobial-Resistant Microorganisms in Hospitals. A challenge to hospital leadership.

OBJECTIVE: To provide hospital leaders with strategic goals or actions likely to have a significant impact on antimicrobial resistance, outline outcome and process measures for evaluating progress toward each goal, describe potential barriers to success, and suggest countermeasures and novel improvement strategies. PARTICIPANTS: A multidisciplinary group of experts was drawn from the following areas: hospital epidemiology and infection control, infectious diseases (including graduate training programs), clinical practice (including nursing, surgery, internal medicine, and pediatrics), pharmacy, administration, quality improvement, appropriateness evaluation, behavior modification, practice guideline development, medical informatics, and outcomes research. Representatives from appropriate federal agencies, the Joint Commission on Accreditation of Healthcare Organizations, and the pharmaceutical industry also participated. EVIDENCE: Published literature, guidelines, expert opinion, and practical experience regarding efforts to improve antibiotic utilization and prevent and control the emergence and dissemination of antimicrobial-resistant microorganisms in hospitals. CONSENSUS PROCESS: Participants were divided into two quality improvement teams: one focusing on improving antimicrobial usage and the other on preventing and controlling transmission of resistant microorganisms. The teams modeled the process a hospital might use to develop and implement a strategic plan to combat antimicrobial resistance. CONCLUSIONS: Ten strategic goals and related process and outcome measures were agreed on. The five strategic goals to optimize antimicrobial use were as follows: optimizing antimicrobial prophylaxis for operative procedures; optimizing choice and duration of empiric therapy; improving antimicrobial prescribing by educational and administrative means; monitoring and providing feedback regarding antibiotic resistance; and defining and implementing health care delivery system guidelines for important types of antimicrobial use. The five strategic goals to detect, report, and prevent transmission of antimicrobial resistant organisms were as follows: to develop a system to recognize and report trends in antimicrobial resistance within the institution; develop a system to rapidly detect and report resistant microorganisms in individual patients and ensure a rapid response by caregivers; increase adherence to basic infection control policies and procedures; incorporate the detection, prevention, and control of antimicrobial resistance into institutional strategic goals and provide the required resources; and develop a plan for identifying, transferring, discharging, and readmitting patients colonized with specific antimicrobial-resistant pathogens.

Anti-Bacterial Agents↗

The pathogenic role of Staphylococcus epidermidis capsular polysaccharide/adhesin in a low-inoculum rabbit model of prosthetic valve endocarditis.

BACKGROUND: The capsular polysaccharide/adhesin (PS/A) antigen of Staphylococcus epidermidis was required to produce endocarditis in a rabbit model in which infection resulted from hematogenous spread of bacteria from a contaminated catheter in the jugular vein. However, many prosthetic valve endocarditis (PVE) infections probably result from direct contamination of the valve with small numbers of bacteria during surgery. The role of PS/A in this situation was evaluated by modifying a rabbit model of endocarditis to partially mimic PVE. METHODS AND RESULTS: A Teflon catheter was contaminated with graded inocula of either PS/A-positive S epidermidis strain M187sp11 or the PS/A-negative, isogenic strain M187sn3 and inserted into the left ventricle through the aortic valve. The PS/A-positive strain had a 50% infectious dose of 1.1 x 10(2) cfu (95% CI, 3.3 to 3.7 x 10(3)) compared with 8.5 x 10(4) cfu of the PS/A-negative strain (95% CI, 8.6 x 10(3) to 8.5 x 10(5)). The odds for developing endocarditis were estimated to be 42 times higher for any given inoculum level of the PS/A-positive strain (P = .1). When the PS/A-positive strain was adherent to a catheter surface it survived in rabbit blood, whereas under the same conditions the PS/A-negative strain was killed approximately 90% in 1 hour. CONCLUSIONS: Direct contamination of an intraventricular foreign body by low levels of PS/A-positive S epidermidis results in endocarditis in rabbits, but at suitably high doses PS/A-negative strains have sufficient virulence to infect cardiac vegetations. PS/A enhances but is not absolutely required for bacterial virulence in a rabbit model of PVE.

Animals↗

Reducing the spread of antimicrobial-resistant microorganisms. Control of vancomycin-resistant enterococci.

Strategies to reduce the spread of hospital-acquired microorganisms resistant to multiple antimicrobial agents are discussed. Because hospitals have experienced a rapid increase in the incidence of infection and colonization with vancomycin-resistant enterococci (VRE) in the past 5 years, the Hospital Infection Control Practices Advisory Committee of the Centers for Disease Control and Prevention has issued recommendations for preventing the spread of vancomycin resistance. Controlling VRE dissemination in pediatric patients requires prompt detection of VRE by microbiology laboratories, education of staff and families about VRE, use of infection control measures to prevent person-to-person VRE transmission, and prudent vancomycin use.

Child↗

Potentiation of Staphylococcus epidermidis catheter-related bacteremia by lipid infusions.

Lipid infusions given to low-birth-weight neonates are associated with coagulase-negative staphylococcal bacteremia. A rabbit model of catheter-related Staphylococcus epidermidis bacteremia was used to compare infection rates between animals receiving 20% lipid infusions with those receiving 10% glucose infusions. Bacterial growth was detected in 43 (66%) of 65 blood cultures obtained during lipid infusions but only 6 (7%) of 91 blood cultures obtained during glucose infusions (P < .001). S. epidermidis was cultured from 7 of 9 catheters recovered from lipid-infused rabbits but from only 3 of 13 catheters from glucose-infused rabbits (P = .016). Lipid but not glucose solutions containing low levels of protein (0.1%-1.0%) supported the survival and growth of S. epidermidis. These results suggest that lipids contribute to the survival and growth of S. epidermidis on contaminated catheters, enhancing the potential of these organisms to disseminate and cause bacteremia.

Animals↗

Coagulase-negative staphylococcal bacteremia among very low birth weight infants: relation to admission illness severity, resource use, and outcome.

OBJECTIVE: To examine the impact of admission-day illness severity on nosocomial bacteremia risk after consideration of traditional risk determinants such as birth weight and length of stay. METHODS: The hospital courses for 302 consecutive very low birth weight (less than 1500 g) infants admitted to two neonatal intensive care units were examined for the occurrence of nosocomial coagulase-negative staphylococcal bacteremia. Using both cumulative incidence and incidence density as measures of bacteremia risk, we explored the relation between illness severity (as measured by the Score for Neonatal Acute Physiology [SNAP]) and bacteremia both before and after birth weight adjustment. In addition, the effect of bacteremia on hospital resource use was estimated. RESULTS: Coagulase-negative staphylococcus was the most common pathogen noted in blood cultures drawn at 48 hours after admission or later. It was isolated on at least one occasion in 53 patients (cumulative incidence of 17.5 first episodes per 100 patients). These episodes occurred during 7652 days at risk, giving an incidence density of 6.9 initial bacteremias per 1000 patient-days at risk. As expected, when compared with the nonbacteremic group, bacteremic patients were of lower birth weight (888 +/- 231 vs 1127 +/- 258 g; P < .01) and gestational age (26.4 +/- 2.1 vs 28.9 +/- 2.8 weeks; P < .01). In addition, these patients were more severely ill on admission (SNAP 17.3 +/- 6.5 vs 12.2 +/- 5.8; P < .01). Even after birth weight stratification, the risk of bacteremia by both measures increased with higher SNAP scores. For example, among infants with birth weights greater than 1 kg, 25% of the most severely ill patients (SNAP 20 and higher) experienced at least one bacteremic episode, whereas the rates seen in infants with intermediate (SNAP 10 to 19) and low illness severity (SNAP 0 to 9) were 8.6% and 3.0%, respectively (chi 2 for trend = 7.25; P < .01). Multivariate linear regression showed that bacteremia was associated with a prolongation of neonatal intensive care unit stay of 14.0 +/- 4.0 days (P < .01) and an increase in hospital charges of $25,090 +/- 12,051 (P < .05), even after adjustment for birth weight and admission-day SNAP. CONCLUSIONS: Nosocomial coagulase-negative bacteremia is an important complication among very low birth weight infants. Assessment of illness severity with SNAP provides information regarding nosocomial infection risk beyond that available from birth weight alone.

Bacteremia↗

Quality of care for preschool children with asthma: the role of social factors and practice setting.

OBJECTIVE: To determine whether patient race or source of payment is associated with differences in the quality of inpatient and outpatient treatment for young children with asthma. DESIGN: Structured medical record review. SETTING: Tertiary care pediatric hospital. PATIENTS: We studied 354 patients aged 1 to 6 years discharged with asthma between October 1, 1989 and September 30, 1990. MEASURES: We developed indicators of the quality of asthma care provided before and during hospitalization and planned after discharge. Outpatient indicators were the use of inhaled beta-agonists and the use of preventive anti-inflammatory medications (inhaled steroids or cromolyn sodium) before admission. In-hospital indicators were the intensity of inhaled beta-agonist therapy in the emergency department and length of stay. Planning for post-hospital care was assessed by the prescription of a nebulizer for home use. We examined associations between these indicators and patient race and source of payment, and explored the influence of primary-care practice type on these associations. RESULTS: After adjustment for potential confounders, we found that Hispanic patients were less likely than white patients to have taken inhaled beta-agonists before admission. Both black and Hispanic patients were less likely than white patients to have taken anti-inflammatory medications. When we adjusted for the patients' primary-care practice type, the effect of patient race did not persist for these indicators of outpatient care. We found no differences by patient race in emergency department care or length of hospital stay. However, black and Hispanic patients were much less likely to be prescribed a nebulizer for home use upon discharge. After adjustment for confounders, there were no differences in the quality of asthma care by source of payment. CONCLUSIONS: We found that young children of racial minorities admitted for an asthma exacerbation were less likely to have received maximally effective preventive therapy. We also identified marked differences in the quality of care planned after hospital discharge for black and Hispanic patients, compared with white patients. Particularly in an era of health reform, attention should focus on barriers to high-quality care for underserved children, who are already at high risk for asthma-related morbidity.

Adrenergic beta-Agonists↗

CRIB and SNAP.

Explore the source record for details and available documents.

Humans↗

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↗

Estimating neonatal mortality risk: an analysis of clinicians' judgments.

BACKGROUND: Clinicians' estimates of mortality risk in the neonatal intensive care unit (NICU) have implications for patient triage, transfer, initiation and termination of life support, and allocation of medical resources. The accuracy of these judgments has not been studied, nor the differences between nurses and attending physicians. OBJECTIVES: 1) evaluate the accuracy of subjective judgments of NICU unit mortality risk, 2) identify the key components of clinician judgments, 3) compare accuracy between attending physicians and nurses, and 4) examine the utility of combining an objectively computed risk and clinician judgments to improve predictions. METHODS: We obtained estimates of mortality risk on 544 admissions to two NICUs on the day of admission from the attending physician and primary nurse. These were compared with an objective computed mortality risk based on birth weight and the Score for Neonatal Acute Physiology (SNAP) using a linear judgment analysis model, as well as with actual outcomes. RESULTS: Physicians and nurses had good discriminating power with actual mortality rates ranging from 0% among low risk patients to 67% among those with the highest mortality estimates. Physicians had a tendency to overestimate mortality risk. Clinicians base their estimates on the same factors and similar judgment weights as the empiric mortality risk model (22% birth weight, 62% illness severity (SNAP), 13% low Apgar, and 3% for intrauterine growth restriction). Clinicians place additional emphasis on therapeutic as well as physiologic factors. When the computed risk and physician judgment were combined, both made significant contributions in a logistic mortality risk model. CONCLUSIONS: Clinician judgments of mortality risk are fairly accurate and similar to an objective illness severity index. This simple method provides insight into clinical decision making and has important applications in improving direct patient care, appropriate allocation of medical resources, and medical training.

Clinical Competence↗