"Infection in the Compromised Host" has become a classic chapter in textbooks devoted to infectious diseases and internal medicine. The numbers of compromised hosts are increasing in the era of modem medicine because of our expanded capabilities to deal with difficult diseases, especially neoplasms. As a consequence, microbiologic complications related to the intensive care administered to these patients are increasing as well. Under these circum- stances, not only does the underlying illness create conditions favorable for the development of unusual infections, but often the therapy contributes to the acquisition of potential pathogens that tum into agents responsible for severe and frequently fatal disease. Granulocytopenia and immunosuppression have been the two key factors in predisposing patients with cancer and other serious diseases to severe bacterial infections. Colonization by hospital-acquired pathogens and breaks in the anatomic barriers-as a result of disease or medical intervention-have contributed to the high incidence of infectious diseases in these patients. Although there is some overlap between the types of infection in granulocytopenic and immunosuppressed hosts, each of these clinical entities has distinctive features thatjustify considering them separately, reserving the term immunocompromised hosts only when refer- ring to patients who are predisposed to opportunistic infections. For about two decades, infections in granulocytopenic patients have attracted the atten- tion of clinicians because they represent a model for the study of antimicrobial drugs in hosts deprived of an essential element of defense against bacterial infection, that is, an adequate number of normally functioning granulocytes.
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1 Introduction.- 2 Epidemiology and Prevention of Infection in the Compromised Host.- 1. Infection As It Relates to Defects in Host Defense.- 1.1. Granulocytopenia.- 1.2. Cellular Immune Dysfunction.- 1.3. Humoral Immune Dysfunction.- 1.4. Obstruction to Natural Body Passages.- 1.5. Breech of Body Barriers.- 2. Origin of Infecting Organisms.- 2.1. Shifts in Microbial Flora.- 2.2. Sources of Acquisition of Exogenous Organisms.- 3. Infection Prevention: Effective but Complex Techniques.- 3.1. Reverse Isolation in Laminar Airflow Rooms or Other Forms of Complete Barrier Isolation.- 3.2. Microbial Suppression with Oral Nonabsorbable Antibiotics.- 3.3. Combined Use of Laminar Airflow Room or Similar Isolation plus Microbial Suppression with Oral Nonabsorbable Antibiotics.- 3.4. Prophylactic Granulocyte Transfusions.- 4. Ineffective Techniques of Infection Prevention.- 5. “Simplified” and Effective Techniques of Infection Prevention.- 6. Suppression of Potential Pathogens.- 6.1. Granulocytopenia.- 6.2. Prophylactic Trials.- 6.3. Other Prophylactic Trials Using Trimethoprim-Sulfamethoxazole.- 6.4. Disadvantages of Selective Microbial Modulation.- 6.5. Fungal Prophylaxis.- 6.6. Oral Antifungal Agents (Nonabsorbable).- 6.7. Skin.- 6.8. Dental Hygiene.- 7. Cellular Immune Dysfunction.- 7.1. Tuberculosis.- 7.2. Pneumocystis carinii.- 7.3. Varicella-Zoster Virus.- 7.4. Herpes Simplex Virus.- 8. Humoral Immune Dysfunction.- 9. Relief of Obstruction.- 10. Care in the Breeching of Body Barriers.- 11. Staff Education.- 12. Patient Education.- References.- 3 Defects in Host-Defense Mechanisms.- 1. Colonization.- 2. The First Line of Defense.- 2.1. The Skin.- 2.2. The Mucosa.- 3. The Second Line of Defense.- 3.1. Humoral Defense Mechanisms.- 3.2. Cellular Defense Mechanisms.- 4. Factors Influencing the Quality of Host Defense.- 4.1. Genetic Control of Host Defense against Infection.- 4.2. Nutritional Status.- 4.3. Age and Host Defense.- 4.4. Body Temperature and Host Defense.- 5. Diseases Affecting Host Defense.- 5.1. Leukemia and Lymphoma.- 5.2. Splenectomy.- 5.3. Sickle Cell Anemia.- 5.4. Diabetes Mellitus.- 5.5. Chronic Renal Failure.- 5.6. Alcoholism and Hepatic Cirrhosis.- 5.7. Systemic Lupus Erythematosus, Rheumatoid Arthritis, and Felty Syndrome.- 5.8. Infections.- 6. Immunosuppressive Drugs.- 6.1. Glucocorticosteroids.- 6.2. Other Immunosuppressive Agents.- 7. Radiation.- 8. Attempts to Strengthen Host Defense.- References.- 4 Fever and Septicemia.- 1. Introduction.- 2. Criteria for Fever, Fever of Undetermined Origin, and Septicemia.- 3. Pathogenesis of Fever.- 4. Syndrome-Oriented Approach to Fever and Suspected Infection: Differential Diagnosis.- 5. Some Emerging Pathogens in the Immunocompromised Host.- 6. Clinical Approach to Fever: History and Physical Examination.- 7. Interaction between the Clinician and the Microbiology Laboratory.- 8. Specific Laboratory Studies.- 9. Diagnosis of Infection: Antibody Measurements and Skin Tests.- 10. Noninvasive Diagnostic Procedures.- 11. Invasive Diagnostic Procedures.- 12. Diagnostic Tests of Limited Usefulness.- 13. Persistent or Recurrent Fever in the Patient with Negative Cultures: Diagnostic Considerations.- 14. Findings Suggestive of Microbial Infection Rather Than Fever Secondary to Underlying Disease.- 15. Initial or Empirical Antimicrobial Therapy: Indications for Treatment.- 16. Relationship of Antimicrobial Therapy and Underlying Disease to Outcome of Infection.- 17. Factors Underlying Recommendation of Initial or Empirical Antimicrobial Therapy Regimens.- 18. Antimicrobial Agents.- 18.1. Aminoglycosides.- 18.2. Antipseudomonal Penicillins.- 18.3. Cephalosporins.- 18.4. Antistaphylococcal Semisynthetic Penicillins.- 19. Is Specific Antistaphylococcal Therapy Necessary?.- 20. Alteration of Empirical Therapy after Documentation of Bacterial Infection.- 21. Role of Other Antibacterial Agents in Therapy.- 22. Therapeutic Drug Monitoring.- 23. Management of Catheter-Associated Infection.- 24. Should Fever Be Suppressed?.- 25. Therapy of Underlying Disease during Documented Infection.- 26. Duration of Antimicrobial Therapy in Documented Infection.- 27. Undocumented Infection and the Decision to Continue or Withhold Antimicrobial Agents.- 28. Recommendations for Continuing or Discontinuing Antimicrobial Therapy and Initiating Empirical Antifungal Therapy.- References.- 5 Dermatologic Manifestations of Infection in the Compromised Host.- 1. Introduction.- 2. Skin as a Barrier to Infection.- 3. Types of Skin Infection.- 3.1. Primary Skin Infection with Common Pathogens.- 3.2. Unusually Widespread Cutaneous Infection.- 3.3. Opportunistic Primary Cutaneous Infection.- 3.4. Systemic Infection Metastatic to Cutaneous and Subcutaneous Sites.- 4. Dermatologie Lesions Associated with AIDS.- 5. Diagnostic Considerations of Skin Infections in the Compromised Patient.- References.- 6 Etiology and Management of the Compromised Patient with Fever and Pulmonary Infiltrates.- 1. Febrile Pneumonitis Syndrome and Its Importance.- 2. Epidemiologic Clues to the Diagnosis of Pulmonary Infection.- 3. Clinical Clues to the Diagnosis of Pulmonary Infection.- 4. Clinical Clues to the Diagnosis of Noninfectious Causes of Febrile Pneumonitis Syndrome.- 4.1. Radiation Pneumonitis.- 4.2. Drug-Induced Pneumonitis.- 4.3. Neoplastic Pulmonary Invasion.- 4.4. Other Noninfectious Causes of Febrile Pneumonitis Syndrome.- 5. Radiologic Clues to the Diagnosis of Febrile Pneumonitis Syndrome.- 6. Definitive Diagnosis.- 6.1. Immunologic Techniques.- 6.2. Conventional Sputum Examination.- 6.3. Transtracheal Aspiration.- 6.4. Invasive Diagnostic Techniques.- 7. Pulmonary Infiltrates in the Patient with AIDS.- 8. Superinfection.- References.- 7 Central Nervous System Infections in the Compromised Host.- 1. Introduction.- 2. Microorganisms.- 2.1. Bacteria.- 2.2. Fungi.- 2.3. Parasites.- 2.4. Viral Infections.- 3. Clinical Presentation: The Approach to the Patient.- 3.1. Meningitis’.- 3.2. CNS Infections Complicating AIDS.- References.- 8 Fungal Infections in the Compromised Host.- 1. Introduction.- 2. Diagnostic Approach: A General Overview.- 2.1. Histology.- 2.2. Cultures.- 2.3. Serology.- 3. Candidiasis.- 3.1. Candida Species.- 3.2. Clinical Presentation.- 4. Aspergillosis.- 5. Mucormycosis.- 5.1. Mucoraceae.- 5.2. Clinical Presentation.- 6. Cryptococcosis.- 6.1. Cryptococcus neoformans.- 6.2. Clinical Presentation.- 7. Coccidioidomycosis.- 7.1. Coccidioides immitis.- 7.2. Clinical Presentation.- 8. Histoplasmosis.- 8.1. Histoplasma capsulatum.- 8.2. Clinical Presentation.- 9. Other Fungal Infections.- 10. Prevention of Opportunistic Fungal Infection.- 10.1. General Considerations.- 10.2. Chemoprophylaxis.- 10.3. Isolation.- 11. Antifungal Therapy.- 11.1. Antifungal Agents.- 11.2. Current Controversies in the Management of Fungal Infections in the Immunocompromised Host.- 12. Perspectives for the Future.- References.- 9 Mycobacterial and Nocardial Infections in the Compromised Host.- 1. Introduction.- 2. Mycobacteria.- 2.1. Classification and Microbiology.- 2.2. Host Defenses.- 2.3. Skin Testing.- 2.4. Pathogenesis.- 2.5. Epidemiology.- 2.6. Clinical Features.- 2.7. Management of Mycobacterial Infections.- 3. Nocardia.- 3.1. Classification and Microbiology.- 3.2. Epidemiology and Pathogenesis.- 3.3. Clinical Features and Diagnosis.- 3.4. Therapy.- 3.5. Infection Caused by Related Organisms.- References.- 10 Parasitic Diseases in the Compromised Host.- 1. Introduction.- 2. Pneumocystis carinii Pneumonia.- 2.1. Historic Perspective.- 2.2. The Organism.- 2.3. Histopathology.- 2.4. Conditions Associated with Pneumocystosis in Humans and Animals.- 2.5. Predisposing Factors and Host-Defense Mechanisms.- 2.6. Epidemiology and Transmission.- 2.7. Clinical Features (Non-AIDS Related).- 2.8. Radiologic Findings.- 2.9. Diagnostic Approaches to Suspected Pneumocystis carinii Infection.- 2.10. Treatment.- 2.11. Patient Isolation and Prophylaxis of Pneumocystis Infection.- 2.12. Postinfection Fibrosis.- 2.13. Overview of Therapeutic and Prophylactic Approaches.- 3. Babesiosis.- 3.1. Clinical Features.- 3.2. Laboratory Diagnosis.- 3.3. Treatment.- 4. Giardiasis.- 4.1. The Organism.- 4.2. Epidemiology.- 4.3. Pathogenesis.- 4.4. Clinical Manifestations.- 4.5. Giardiasis in the Compromised Host.- 4.6. Diagnosis.- 4.7. Treatment.- 5. Toxoplasmosis.- 5.1. History.- 5.2. The Organism.- 5.3. Pathogenesis.- 5.4. Signs and Symptoms of Toxoplasmosis in Immunologically Intact Patients.- 5.5. Toxoplasmosis in the Compromised Host.- 5.6. Toxoplasmosis in AIDS Patients.- 5.7. Diagnosis.- 5.8. Summary of Diagnostic Approach to Possible CNS Toxoplasmosis.- 5.9. Therapy.- 5.10. Prevention.- 6. Coccidial Infections.- 7. Strongyloidiasis.- 7.1. The Organism.- 7.2. Clinical Manifestations.- 7.3. Diagnosis.- 7.4. Treatment.- References.- 11 Legionellosis in the Compromised Host.- 1. Introduction.- 2. Microbiology.- 2.1. Classification.- 2.2. Morphology.- 2.3. Cultural and Biochemical Characteristics.- 3. Pathology, Pathogenesis, and Immunology.- 3.1. Pathology and Pathogenesis.- 3.2. Immunology.- 4. Epidemiology.- 4.1. General Considerations.- 4.2. Ecology.- 4.3. Nosocomial Legionellosis.- 5. Clinical Manifestations.- 5.1. Symptoms.- 5.2. Signs.- 5.3. Laboratory Findings.- 5.4. Radiographic Findings.- 5.5. Extrapulmonary Complications.- 6. Diagnosis.- 6.1. Differential Diagnosis.- 6.2. Dual Infection.- 6.3. Specific Diagnosis.- 6.4. Diagnostic Approach.- 7. Treatment.- 7.1. Retrospective Studies.- 7.2. Animal Studies.- 7.3. Factors Determining Antimicrobial Efficacy.- 7.4. Recommendations.- 7.5. Course.- 8. Prevention and Control.- References.- 12 Viral Hepatitis in the Compromised Host.- 1. Introduction.- 2. Role of Immunologic Mechanisms in the Pathogenesis of Viral Hepatitis.- 2.1. Hepatitis B.- 2.2. Non-A, Non-B Hepatitis.- 3. Viral Hepatitis in the Immunocompromised Host.- 3.1. Hemodialyzed Patients with Chronic Renal Failure.- 3.2. Hepatitis in Recipients of Organ Transplants.- 3.3. Hepatitis in Oncology Patients.- 4. Prevention.- 5. Summary.- References.- 13 Herpes Group Virus Infections in the Compromised Host.- 1. Introduction.- 2. Herpes Simplex Virus.- 2.1. Clinical Epidemiology and Patterns of Infection.- 2.2. Pathogenesis.- 2.3. Diagnosis and Therapy.- 3. Varicella-Zoster Virus.- 3.1. Clinical Epidemiology and Patterns of Infection.- 3.2. Pathogenesis.- 3.3. Diagnosis and Therapy.- 4. Cytomegalovirus.- 4.1. Clinical Epidemiology and Patterns of Infection.- 4.2. Pathogenesis.- 4.3. Diagnosis and Therapy.- 5. Epstein-Barr Virus.- 5.1. Clinical Epidemiology and Patterns of Infection.- 5.2. Pathogenesis.- 5.3. Diagnosis and Therapy.- 6. Other Human Herpesviruses.- References.- 14 Morbidity in Compromised Patients Due to Viruses Other Than Herpes Group and Hepatitis Viruses.- 1. Introduction.- 2. DNA Viruses.- 2.1. Adenoviruses.- 2.2. Papovaviruses.- 2.3. Vaccinia.- 3. RNA Viruses.- 3.1. Picornaviruses.- 3.2. Paramyxoviruses.- 3.3. Rotaviruses.- 3.4. Human T-Lymphotropic Viruses.- References.- 15 Acquired Immunodeficiency Syndrome.- 1. Introduction.- 2. Epidemiology.- 2.1. Case Definition.- 2.2. AIDS in the United States and Europe.- 2.3. AIDS in Africa and the Caribbean.- 3. Etiology and Pathogenesis.- 3.1. Human T-Lymphotropic Retroviruses.- 3.2. Immunologic Features.- 4. Risk Groups for AIDS and HIV Infection.- 5. Clinical Features.- 5.1. General.- 5.2. Clinical Approach to Fever in AIDS and in Population Groups at Increased Risk.- 6. Laboratory Studies in AIDS and HIV-Related Syndromes.- 6.1. Routine Diagnostic Studies.- 6.2. Specific Serologic and Immunologic Tests.- 6.3. Cultures.- 6.4. Other Studies.- 7. Differential Diagnosis.- 7.1. General.- 7.2. Homosexual and Bisexual Males.- 7.3. Women.- 7.4. Intravenous Drug Users.- 7.5. Blood Product and Organ Transplant Recipients.- 7.6. Pediatric Age Group.- 8. Therapy.- 8.1. General Approach.- 8.2. Management of Infection.- 8.3. Presentation and Management of Common Opportunistic Infections.- 8.4. Immunotherapy and Antiretroviral Therapy.- 9. Hospital Infection Control and Protection of Health Workers.- 10. Appendix.- References.- 16 Infections Complicating Congenital Immunodeficiency Syndromes.- 1. Introduction.- 2. Aim of Therapy in Congenital Immunodeficiency Diseases.- 2.1. Treatment of Life-Threatening Infections.- 2.2. Minimizing the Effects of Less Severe Acute Infections.- 2.3. Prevention of Chronic Infections and Their Sequelae.- 3. Specific Infections in Immunodeficiency Syndromes.- 3.1. Combined B- and T-Cell Defects.- 3.2. Pure T-Cell Congenital Immunodeficiencies.- 3.3. B-Cell Immunodeficiency.- 3.4. Complement Component Deficiencies.- 3.5. Phagocyte Abnormalities.- References.- 17 Diagnosis and Management of Infectious Disease Problems in the Child with Malignant Disease.- 1. Cancers of Childhood.- 2. Interface between Cancer and Infection.- 3. Perturbations of Host Defenses That Contribute to the Risk of Infection in Children with Cancer.- 4. Fever in Childhood Cancer.- 5. Primary Causes of Fever and Infection in the Granulocytopenic Child.- 5.1. Bacteria.- 5.2. Viruses.- 5.3. Fungi.- 5.4. Protozoa.- 6. Diagnostic Evaluation of the Febrile Child with Cancer.- 7. Is There a Correct Starting Regimen for Granulocytopenic Children Who Become Febrile?.- 8. When Is It Appropriate to Modify the Initial Empirical Antibiotic Regimen?.- 9. If a Microbial Isolate Is Identified and the Antibiotic Sensitivities Are Known, Should the Antibiotic Spectrum Be Narrowed?.- 10. If the Patient Has a Bacteremia and Also Has an Indwelling Catheter, Are Additional Modifications of Therapy Necessary?.- 11. Do the Principles Gleaned from the Management of Intravascular Catheters Apply to Other Types of Foreign Bodies?.- 12. What Is the Role of Invasive Diagnostic Procedures in the Evaluation and Management of the Febrile Child with Cancer?.- 13. Are There Situations in Which Surgery Should be Incorporated into the Management Plan, Even if the Patient is Profoundly Granulocytopenic?.- 14. How Long Should Antibiotic Therapy Be Continued, and How Should It Be Modified When the Clinical and Microbiologic Evaluation Has Failed to Reveal an Infectious Etiology for Fever?.- 15. Summary.- References.- 18 Management of Infections in Leukemia and Lymphoma.- 1. Introduction.- 2. Host Defenses against Infection in Leukemias and Lymphomas.- 3. The Role of Infection in Mortality from Leukemia and Lymphoma.- 4. Problems with the Interpretation of Fever and Infection Incidence Data in Neutropenic States.- 5. Causes of Fever in Leukemia and Lymphoma.- 6. Site of Involvement and the Nature of the Microbial Pathogen(s).- 7. Synthesis.- 8. Summary of Recommended Therapeutic Strategies.- 8.1. Different Approaches to Leukemia and Lymphoma.- 8.2. Environmental Considerations.- 8.3. Prophylactic Antibiotics.- 8.4. Systemic Antimicrobial Agents.- 9. Approach to the Splenectomized Patient.- 10. Neutrophil Transfusions in the Treatment and Prophylaxis of Infection.- 11. Immunoprophylaxis and Immunotherapy of Infection.- 11.1. Childhood Immunizations.- 11.2. Passive Antibody.- 11.3. Influenza Immunization.- 11.4. Pneumococcal Immunization.- References.- 19 Evaluation and Management of Infections in Patients with Collagen Vascular Disease.- 1. Introduction.- 2. Novel Features of Host-Microorganism Interactions in CVD.- 3. Morbidity and Mortality Caused by Infections in Patients with CVD.- 4. Host Abnormalities as Potential Contributing Factors to Infections in Patients with CVD.- 5. Role of Immunosuppressive Therapy in Predisposing Patients with CVD to Infections.- 6. Spectrum of Infection in Patients with CVD.- 7. Unique Clinical Features of Infection in Patients with CVD.- 8. Clinical Examples of Infection and Their Management.- 8.1. Altered Mental Status in a Patient with SLE.- 8.2. Pleuritic Chest Pain and Fever in a Patient with SLE.- 8.3. Abdominal Pain in a Patient with SLE.- 8.4. Painful Knee in a P...
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