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Biomedical subjects

D E Craven

Publications and source records attributed to D E Craven.

105 records · Page 6Linked to original sources

Adherence of isolates of Neisseria meningitidis from patients and carriers to human buccal epithelial cells.

An in vitro assay was used to study the adherence of Neisseria meningitidis to human buccal epithelial cells. Both unencapsulated and encapsulated, piliated isolates obtained from throats of asymptomatic carriers demonstrated significantly higher levels of adherence to buccal cells than encapsulated, piliated isolates obtained from the blood and cerebrospinal fluid of patients (P < 0.001). Meningococcal adherence to buccal cells could not be correlated to a specific capsular polysaccharide serogroup, outer membrane protein serotype, or quantitative differences in pili. However, the data suggested that capsular polysaccharide impedes the adherence of meningococci to buccal cells, and the significantly smaller amount of capsular polysaccharide extracted from carrier isolates compared with case isolates (P < 0.001) could explain differences in meningococcal adherence to buccal cells. Increased adherence may facilitate host colonization, promote nasopharyngeal carriage, and possible reflect altered pathogenicity.

Antigens, Surface↗

Adult bacteremia caused by gram-negative bacilli.

Because gram-negative bacteremia is increasing in frequency, it is important for physicians to suspect, carefully evaluate, and initiate early appropriate therapy. Identification of the probable source of bacteremia and a knowledge of the hospital microflora are helpful in guiding antibiotic selection. The mortality of gram-negative bacteremia tends to vary with the severity of the underlying disease and, accordingly, tends to be low in obstetrical patients. Prevention is the most effective method of controlling these infections and, therefore, care and discretion when employing invasive devices is essential. With the increasing incidence of these infections and the increased threat of antibiotic plasmid resistance, future infection control in high-risk patients by immunoprophylaxis may be necessary.

Anti-Bacterial Agents↗

Protection against group B meningococcal disease: evaluation of serotype 2 protein vaccines in a mouse bacteremia model.

A mouse bacteremia model was used to evaluate the immunogenicity and protection against challenge provided by five different meningococcal serotype 2 vaccines. Mice vaccinated with serotype 2 protein vaccines had levels of bacteremia reduced by at least 100-fold after challenge with group B serotype 2 miningococci. Mice vaccinated with serotype 2 protein vaccine and challenged with group C serotype 2 meningococci showed 10-fold or less reduction in bacteremia. Vaccines were primarily serotype specific since no increase in protection was observed after challenge with either group B serotype 4 or group C nontypable meningococci. Serotype 2 antibody levels, measured by the bactericidal assay and the enzyme-linked immunosorbent assay 3 weeks after immunization, demonstrated a graded dose-response which correlated with protection up to 40 weeks after vaccination with a single 10- or 25-micrograms dose of serotype 2 protein vaccine. A 1-microgram booster dose of serotype 2 vaccine, given 2 weeks after primary immunization, significantly increased both bactericidal (P less than 0.01) and enzyme-linked immunosorbent assay (P less than 0.02) titers. The data obtained from the mouse bacteremia model indicate that serotype 2 protein vaccines are stable and immunogenic, and protect mice against challenge with group B serotype 2 meningococci.

Animals↗

Rapid serogroup identification of Neisseria meningitidis by using antiserum agar: Prevalence of serotypes in a disease-free military population.

Nasopharyngeal cultures from 414 Marines were plated directly onto antiserum agar containing the antibiotics vancomycin, colistin, and nystatin for meningococcal isolation and serogroup identification. Meningococci were isolated from 267 Marines, giving a carrier prevalence of 64.5%. A total of 58% of the isolates could be placed into serogroups; of these 22.3% were group B, 4.7% were group C, 25.7% were group Y, 24.3% were group W135, and 23.0% were group 29E. No serogroup A organisms were recovered. Serotyping by agar gel double diffusion was performed on 148 strains. More than 70% of these strains were nontypable, and the disease-associated serotype 2 was present only in two group Y isolates. The same 148 isolates were also classified by major outer membrane protein patterns after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Polyacrylamide gel electrophoresis pattern IV was most common among all serogroups. The data demonstrate the effective use of antiserum agar for meningococcal surveillance and document the frequency of specific serotypes and polyacrylamide gel electrophoresis types among carrier isolates obtained from a nonrecruit military population.

Carrier State↗

Serogroup identification of Neisseria meningitidis: comparison of an antiserum agar method with bacterial slide agglutination.

A serum agar method for serogrouping Neisseria meningitidis is described and compared with conventional bacterial slide agglutination. There was 93% agreement for 300 strains examined individually by each method. Among strains from serogroups A, B, C, Y, and W135, there was 100% correlation, whereas strains from serogroup 29E (Z') had only 67% correlation. The serum agar method was rapid, as well as easy to perform and interpret. The potential benefits of this method for epidemiological studies and reference laboratories processing large numbers of meningococcal isolates are emphasized.

Agglutination Tests↗

Cross-reactive antigens: their potential for immunization-induced immunity to Gram-negative bacteria.

The involvement of multiple species and serologic types in gram-negative bacteremia prompted evaluation of immunization with shared, cross-reactive antigens of gram negative bacilli. Active and passive immunization with Re chemotype mutants of Salmonella minnesota afforded significant protection against heterologous gram-negative bacilli and were considerably more effective than immunization with smooth S. minnesota or its Ra, Rb, Rc, Rd1 and Rd2 mutants. Since the lipopolysaccharide of the Re mutant is composed solely of 2-keto-3-deoxycotonate (KDO) and lipid A, the protective activity of antibody to the Re mutant and lipid A was evaluated. Immunization with Re mutant protected granulocytopenic rabbits against lethal bacteremia and protected mice against lethal challenge with heterologous endotoxins, whereas antibody to lipid A had no protective activity. In concomitant clinical studies, high titers of antibody to the Re mutant at the onset of bacteremia were associated with a significant diminution in the frequency of shock and death, which was independent of any effect of O-specific antibody.

Animals↗

Central venous catheter infection with Rhodotorula minuta in a patient with AIDS taking suppressive doses of fluconazole.

A case of Rhodotorula minuta central venous catheter infection with fungaemia is described in a patient with advanced acquired immunodeficiency syndrome (AIDS), HIV nephropathy, end-stage renal disease requiring haemodialysis, and a permanent Quinton catheter in place for 6 months. At the time of fungaemia, the patient was taking 100 mg fluconazole per os daily for a previous episode of Candida oesophagitis. R. minuta central venous catheter infection with fungaemia was successfully treated with 455 mg total dose amphotericin B (0.6 mg kg-1 day-1) over 25 days without removal of the catheter. In vitro antifungal susceptibility testing for R. minuta revealed a minimum inhibitory concentration to fluconazole of > 100 micrograms ml-1 and to amphotericin B of 1.2 microgram ml-1. Clinically evident fungaemia, even with an unusual organism such as R. minuta, may occur in patients with intravenous catheters, and while the immunosuppressed patient is receiving azole therapy.

AIDS-Related Opportunistic Infections↗

Validating literature-based models with direct clinical trial results: the cost-effectiveness of secondary prophylaxis for PCP in AIDS patients.

OBJECTIVE: To compare literature-based estimates of the cost-effectiveness ratios of strategies for secondary prophylaxis of Pneumocystis carinii pneumonia (PCP) in AIDS patients with estimates obtained using data from a recent comparative clinical trial. DESIGN: A decision-analytic Markov model with data on drug efficacy and toxicity from both the medical literature and a national randomized clinical trial. Drug costs were from average wholesale prices. Discounted life expectancy, total direct medical costs, and cost-effectiveness were projected in dollars per year of life saved (YLS). SETTING: Hypothetical for the literature-based model, then the clinical trial results from the multicenter AIDS Clinical Trials Group (ACTG Protocol 021). PATIENT POPULATION: Patients with AIDS and a prior episode of PCP. INTERVENTIONS: Strategies included no prophylaxis, TMP-SMX (160/800 mg) daily, or aerosolized pentamidine (300 mg) monthly. Patients experiencing major toxic reactions to either medication would cross over to the other agent. MAIN RESULTS: In the literature-based model no prophylaxis was associated with a projected life expectancy of 1.430 years, and total direct cost of $42,080. TMP-SMX increased life expectancy to 2.051 years and cost to $42,300; for aerosolized pentamidine life expectancy was 2.066 years and cost $43,960. TMP-SMX had an incremental cost-effectiveness ratio of $350 per YLS compared with no prophylaxis; the incremental ratio for aerosolized pentamidine was $2,950 per YLS when compared with no prophylaxis, but rose to $110,880 per YLS compared with TMP-SMX. When data from ACTG clinical trial 021 were utilized in the model, the incremental cost-effectiveness ratio for TMP-SMX compared with no prophylaxis was $720 per YLS; aerosolized pentamidine was not cost-effective, and was "dominated" by TMP-SMX because it was associated with higher costs and shorter life expectancy. CONCLUSIONS: Literature-based cost-effectiveness models are useful in developing health policy before clinical trials are completed. Clinical trial results, when available, can be used to validate and revise these models. For secondary PCP prophylaxis in AIDS patients, TMP-SMX is substantially more cost-effective than aerosolized pentamidine.

AIDS-Related Opportunistic Infections↗

A Monte Carlo simulation of advanced HIV disease: application to prevention of CMV infection.

BACKGROUND: Disagreement exists among decision makers regarding the allocation of limited HIV patient care resources and, specifically, the comparative value of preventing opportunistic infections in late-stage disease. METHODS: A Monte Carlo simulation framework was used to evaluate a state-transition model of the natural history of HIV illness in patients with CD4 counts below 300/mm3 and to project the costs and consequences of alternative strategies for preventing AIDS-related complications. The authors describe the model and demonstrate how it may be employed to assess the cost-effectiveness of oral ganciclovir for prevention of cytomegalovirus (CMV) infection. RESULTS: Ganciclovir prophylaxis confers an estimated additional 0.7 quality-adjusted month of life at a net cost of $10,700, implying an incremental cost-effectiveness ratio of roughly $173,000 per quality-adjusted life year gained. Sensitivity analysis reveals that this baseline result is stable over a wide range of input data estimates, including quality of life and drug efficacy, but it is sensitive to CMV incidence and drug price assumptions. CONCLUSIONS: The Monte Carlo simulation framework offers decision makers a powerful and flexible tool for evaluating choices in the realm of chronic disease patient care. The authors have used it to assess HIV-related treatment options and continue to refine it to reflect advances in defining the pathogenesis and treatment of AIDS. Compared with alternative interventions, CMV prophylaxis does not appear to be a cost-effective use of scarce HIV clinical care funds. However, targeted prevention in patients identified to be at higher risk for CMV-related disease may warrant consideration.

AIDS-Related Opportunistic Infections↗

Guidelines for the management of intravascular catheter-related infections.

These guidelines from the Infectious Diseases Society of America (IDSA), the American College of Critical Care Medicine (for the Society of Critical Care Medicine), and the Society for Healthcare Epidemiology of America contain recommendations for the management of adults and children with, and diagnosis of infections related to, peripheral and nontunneled central venous catheters (CVCs), pulmonary artery catheters, tunneled central catheters, and implantable devices. The guidelines, written for clinicians, contain IDSA evidence-based recommendations for assessment of the quality and strength of the data. Recommendations are presented according to the type of catheter, the infecting organism, and the associated complications. Intravascular catheter-related infections are a major cause of morbidity and mortality in the United States. Coagulase-negative staphylococci, Staphylococcus aureus, aerobic gram-negative bacilli, and Candida albicans most commonly cause catheter-related bloodstream infection. Management of catheter-related infection varies according to the type of catheter involved. After appropriate cultures of blood and catheter samples are done, empirical i.v. antimicrobial therapy should be initiated on the basis of clinical clues, the severity of the patient's acute illness, underlying disease, and the potential pathogen(s) involved. In most cases of nontunneled CVC-related bacteremia and fungemia, the CVC should be removed. For management of bacteremia and fungemia from a tunneled catheter or implantable device, such as a port, the decision to remove the catheter or device should be based on the severity of the patient's illness, documentation that the vascular-access device is infected, assessment of the specific pathogen involved, and presence of complications, such as endocarditis, septic thrombosis, tunnel infection, or metastatic seeding. When a catheter-related infection is documented and a specific pathogen is identified, systemic antimicrobial therapy should be narrowed and consideration given for antibiotic lock therapy, if the CVC or implantable device is not removed. These guidelines address the issues related to the management of catheter-related bacteremia and associated complications. Separate guidelines will address specific issues related to the prevention of catheter-related infections. Performance indicators for the management of catheter-related infection are included at the end of the document. Because the pathogenesis of catheter-related infections is complicated, the virulence of the pathogens is variable, and the host factors have not been well defined, there is a notable absence of compelling clinical data to make firm recommendations for an individual patient. Therefore, the recommendations in these guidelines are intended to support, and not replace, good clinical judgment. Also, a section on selected, unresolved clinical issues that require further study and research has been included. There is an urgent need for large, well-designed clinical studies to delineate management strategies more effectively, which will improve clinical outcomes and save precious health care resources.

Anti-Infective Agents↗

Absence of antibodies to HTLV-III in health workers after hepatitis B vaccination.

A proportion of the plasma for the triply inactivated, plasma-derived hepatitis B vaccine produced in the United States is obtained from homosexual men. Because homosexual men are a high-risk group for the acquired immunodeficiency syndrome (AIDS), concern has emerged that the vaccine could harbor the AIDS agent. To evaluate this risk, we tested 15-month postvaccination serum samples for antibodies to human T-cell lymphotropic virus type III in 100 health care workers who had received inactivated hepatitis B vaccine lots made from plasma collected between 1977 and 1979 and 100 who had received placebo injections. None of the 200 health workers had serological evidence of human T-cell lymphotropic virus type III infection. These serological findings lend additional support to earlier epidemiologic and immunologic observations suggesting that hepatitis B vaccine does not transmit infection with an AIDS virus.

Antibodies, Viral↗

A model clinic for the initial evaluation and establishment of primary care for persons infected with human immunodeficiency virus.

BACKGROUND: The human immunodeficiency virus (HIV)-infected patients on initial presentation to primary medical care may have extensive problems relating to medical, substance abuse, psychiatric, and social issues. We examined a model for the initiation of primary medical care for patients infected with HIV at a public hospital and presented the clinical, educational, and research benefits associated with such a clinic. METHODS: Eight hundred forty-five consecutive HIV-infected outpatients without primary care, who presented to a municipal hospital HIV intake clinic, the Diagnostic Evaluation Unit, between February 1, 1990 and August 31, 1993, received a multidisciplinary assessment and a facilitated access to medical services. The performance of standardized initial clinical evaluation and adherence to primary care referral were examined. RESULTS: During the most recent study year, more than 90% of patients presenting to the clinic completed the intake process and 95% were seen at the site to which they were referred for primary medical care. Tests for CD4 lymphocytes, syphilis, hepatitis B, and tuberculosis were obtained, pneumococcal vaccinations were administered, and social service assessments were performed in 92% to 98% of patients completing the intake. The clinical setting was a site for involvement in research protocols and provided a focused educational experience concerning outpatient HIV management for medical students and residents. CONCLUSIONS: Establishment of a clinic dedicated to the initial evaluation of HIV-infected persons in a municipal hospital successfully evaluated and linked patients to primary care providers. The clinic structure enabled the standardized performance of appropriate laboratory tests and vaccinations and provided unique educational and research opportunities. We encourage other health care settings to consider the development of similar models for the initiation of medical care for persons infected with HIV.

Boston↗