Subject(s)
Ethanol/pharmacology , HIV Infections/drug therapy , HIV Protease Inhibitors/therapeutic use , Antiretroviral Therapy, Highly Active , Cytochrome P-450 Enzyme System/metabolism , Drug Interactions , Ethanol/metabolism , HIV Infections/metabolism , HIV Protease Inhibitors/metabolism , HumansABSTRACT
Vancomycin-resistant Enterococcus (VRE) is a major nosocomial pathogen. We collected clinical and laboratory data on 93 hospitalized adults with VRE bacteremia and 101 adults with vancomycin-susceptible enterococcal (VSE) bacteremia. Risk factors for VRE bacteremia included central venous catheterization, hyperalimentation, and prolonged hospitalization prior to the initial blood culture. VRE-infected patients were less likely to have undergone recent surgery or have polymicrobial bacteremia, suggesting a pathogenesis distinct from traditional VSE bacteremia. Prior exposure to metronidazole was the only significant pharmacologic risk factor for VRE bacteremia. Animal studies suggest metronidazole potentiates enterococcal overgrowth in the gastrointestinal tract and translocation into the bloodstream. An increasing APACHE II score was the major risk factor for death in a multivariate analysis, with VRE status being of only borderline significance.
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/microbiology , Cross Infection/microbiology , Enterococcus/drug effects , Gram-Positive Bacterial Infections/microbiology , Vancomycin/pharmacology , Adult , Aged , Anti-Bacterial Agents/adverse effects , Bacteremia/drug therapy , Bacteremia/etiology , Bacteremia/mortality , Case-Control Studies , Cross Infection/drug therapy , Cross Infection/etiology , Cross Infection/mortality , Drug Resistance, Microbial , Enterococcus/isolation & purification , Enterococcus faecalis/drug effects , Enterococcus faecalis/isolation & purification , Enterococcus faecium/drug effects , Enterococcus faecium/isolation & purification , Female , Gram-Positive Bacterial Infections/drug therapy , Gram-Positive Bacterial Infections/etiology , Gram-Positive Bacterial Infections/mortality , Humans , Intensive Care Units , Male , Metronidazole/adverse effects , Middle Aged , Multivariate Analysis , Risk FactorsABSTRACT
Deciding on postexposure prophylaxis for any infection requires that the patient and healthcare provider understand the magnitude of infection risk and the adverse consequences of therapeutic intervention or nonintervention. Principles of epidemiology and microbiology allow us to estimate the risk of infection. Principles of clinical pharmacology allow us to estimate the risk and benefit of therapy. The dose-response-time relationships for antiviral activity and toxicity of a drug can be used to develop regimens that maximize benefit and minimize risk. Other important pharmacologic considerations include the role of active and toxic drug metabolites, combination chemotherapy, drug interactions, and medication compliance.
Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/prevention & control , Health Personnel , Occupational Exposure/adverse effects , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Biological Availability , Dose-Response Relationship, Drug , Drug Interactions , Drug Therapy, Combination , Food-Drug Interactions , HIV Infections/blood , HIV Infections/etiology , Humans , Patient ComplianceABSTRACT
Human erythrocytes bearing electroinserted full-length CD4 (RBC-CD4) can bind and fuse with a laboratory strain of human immunodeficiency virus type 1 (HIV-1) or with T cells infected by HIV-1. Here we show that RBC-CD4 neutralize primary HIV-1 strains in an assay of cocultivation of peripheral blood mononuclear cells (PBMC) from HIV-1-infected persons with uninfected PBMC. RBC-CD4 inhibited viral p24 core antigen accumulation in these cocultures up to 10,000-fold compared with RBC alone. Viral p24 accumulation was inhibited equally well when measured in culture supernatants or in call extracts. The inhibition was dose-dependent and long-lived. Two types of recombinant CD4 tested in parallel were largely ineffective. The neutralization of primary HIV-1 by RBC-CD4 in vitro was demonstrated in PBMC cultures from 21 of a total of 23 patients tested at two independent sites. RBC-CD4 may offer a route to blocking HIV-1 infection in vivo.
Subject(s)
CD4 Antigens/metabolism , CD4-Positive T-Lymphocytes/virology , Erythrocytes/virology , HIV-1/physiology , Acquired Immunodeficiency Syndrome/blood , Binding, Competitive , CD4 Antigens/genetics , Cells, Cultured , Coculture Techniques , Electroporation , Erythrocyte Membrane/metabolism , HIV Core Protein p24/analysis , Humans , Kinetics , Recombinant Proteins/metabolism , Virus ReplicationSubject(s)
HIV-1/drug effects , Tubercidin/pharmacology , Cell Line , Cells, Cultured , Humans , T-Lymphocytes/microbiologyABSTRACT
Repeated hospital admission is a serious problem for both the patient and the health care system. The life story of a patient repeatedly admitted for treatment of exacerbations of a chronic disease, such as diabetic ketoacidosis, can often be compared to Faulkner's family Sartoris. The Sartoris characters were wholly occupied in the pursuit of their painful decline and eventual demise. At the Johns Hopkins Hospital, 45 persons were identified who were repeatedly admitted to the medical service for diabetic ketoacidosis. Forty-two charts of "recidivist" patients and "non-recidivist" control patients matched for age and severity of disease were reviewed to determine factors that, if corrected, would prevent repeated admission. Case reports of three patients who were admitted an average of 11 times annually for several years are presented. Implications of the "Game of Sartoris" for the American teaching hospital are discussed.
