A wide variety of antimicrobial agents is available to treat established infections caused by bacteria, fungi, viruses, or parasites. This section will cover the general principles of antimicrobial therapy and will also include illustrative clinical problems to emphasize proper decision-making in using antimicrobials.
Toxicity of Antimicrobial Therapy
The mechanisms associated with common adverse reactions to antimicrobials include dose-related toxicity that occurs in a certain fraction of patients when a critical plasma concentration or total dose is exceeded, and toxicity that is unpredictable and mediated through allergic or idiosyncratic mechanisms. For example, certain classes of drugs such as the aminoglycosides are associated with dose-related toxicity.
Nucleoside analogs
Nucleoside analog reverse transcriptase inhibitors have formed the backbone of anti-human immunodeficiency virus therapy for the last decade (see Table Characteristics of Nucleoside Reverse Transcriptase Inhibitors). Reverse transcription is necessary for human immunodeficiency virus RNA to be used as a template to produce viral DNA, which can be integrated into the cellular genome.
Management of Bacterial Meningitis
Meningitis used to be a disease that occurred primarily in children younger than 12 years. The advent of a vaccine for Haemophilus influenzae has led to a marked change in the epidemiology of meningitis in developed countries.
Management of Infective Endocarditis
Infective endocarditis is a microbial infection of the endothelial lining of the heart. The characteristic lesion is a vegetation (a mass comprised of fibrin, platelets, microorganisms and their product or products on a valve leaflet). Multiple valves may be involved, as may any part of the endothelium of the heart.
Management of Tuberculosis
Tuberculosis was a disappearing disease in North America until the early 1980s. However, the spread of human immunodeficiency virus infection has changed that. From 1985 to 1992 there was an increase in the number of cases of tuberculosis reported in the United States, and most of these cases were in New York, New Jersey, Texas, Florida, and California. The other major change in the epidemiology of tuberculosis has been the emergence of multidrug-resistant disease.
Management of Malaria
Malaria is a protozoan (genus Plasmodium) infection transmitted by the bite of an infected female Anopheles mosquito and rarely via a contaminated blood transfusion. It is extremely common, affecting more than 500 million persons and resulting in more than 1 million deaths each year. There are four species of the genus Plasmodium that cause malaria in man.
Erythrocytic asexual phase
This begins with penetration into red blood cells by merozoites arising from the exoerythrocytic schizonts in the liver cells. The parasites grow rapidly, and a large central vacuole forms in the cytoplasm leading to the so-called ring form.
Management of Sepsis
Sepsis, sepsis syndrome, septic shock, and multiorgan dysfunction are all part of a continuum of infection-related systemic illness. Table Definitions for Sepsis, Sepsis Syndrome, Septic Shock and Multiorgan Dysfunction Syndrome gives definitions for each of these entities. The pathogenesis of sepsis is very complex, involving a large number of mediators.
Evaluation of the efficacy of vaccines
Adequate response to immunization is most frequently judged by measuring the development of specific serum immunoglobulins (e.g., antibodies) following a course of administration of vaccine. The concentration of specific immunoglobulin in plasma is usually proportional to the degree of protection from the viral agent.