Inhibition of folate metabolism in chemotherapy : the origins and uses of co-trimoxazole
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Bibliographic Information
Inhibition of folate metabolism in chemotherapy : the origins and uses of co-trimoxazole
（Handbook of experimental pharmacology, v. 64）
Springer-Verlag, 1983
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Available at 31 libraries
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Includes bibliographies and index
Description and Table of Contents
Description
The literature on co-trimoxazole (TMP jSMX) is voluminous, but in the main it consists of research reports. The same can be said of various symposia that have appeared. This volume attempts to present the current status of this antibacterial combination in a series of topical reviews, each of which represents a comprehensive summary of a segment of the field. The editor acknowledges with appreciation the help provided by JACKIE, JENKS, LEE KUYPER, and particularly, RUTH Ross in the preparation of the Subject Index, and thanks Burroughs Wellcome Co. for providing access to library and word processing facilities. Research Triangle Park GEORGE H. HITCHINGS List of Authors Dr. J. F. ACAR, Hospital Saint-Joseph, 7, rue Pierre-Larousse, F-75674 Paris Cedex 14 Dr. N. ANAND, National Information Centre for Drugs and Pharmaceuticals, Central Drug Research Institute, Chattar Manzil, P. O. Box No. 173, Lucknow, 226001jIND Dr. D. W. BARRY, The Wellcome Research Laboratories, Burroughs Wellcome Co. , 3030 Cornwallis Road, Research Triangle Park, NC 27709jUSA Dr. R. E. BLACK, Center for Vaccine Development, University of Maryland, Division of Infectious Diseases, 29 S.
Greene Street, Bressler Building, Room 404, Baltimore, MD 21201jUSA Dr. J. J. BURCHALL, Department of Microbiology, The Wellcome Research Laboratories, Burroughs Wellcome Co. , 3030 Cornwallis Road, Research Triangle Park, NC 27709jUSA Dr. S. R. M. BUSHBY, The Wellcome Research Laboratories, Burroughs Wellcome Co. , 3030 Cornwallis Road, Research Triangle Park, NC 27709jUSA Dr. M. L.
Table of Contents
Trimethoprim/Sulfamethoxazole: An Overview.- A. Introduction.- B. Mechanisms of Action.- C. Resistance.- I. Chromosome-Mediated Resistance.- II. Plasmid-Mediated Resistance.- III. Thymidine Dependence.- D. Clinical Use of TMP/SMX.- I. Approved Indications in the United States.- II. Other Important Uses.- E. Use of TMP or SMX as Single Agents.- F. Adverse Effects.- G. Summary.- References.- Pharmacology and Biochemistry.- 1 Functions of Tetrahydrofolate and the Role of Dihydrofolate Reductase in Cellular Metabolism.- A. General.- B. Occurrence of Folates.- C. Functions of Tetrahydrofolate: Cofactors.- I. Formate and Equivalents.- 1. Purine Biosynthesis.- II. Formaldehyde Equivalents, Hydroxymethyl, and Methyl Derivatives.- 1. Methionine Biosynthesis.- 2. Thymidylate Synthesis.- 3. Vitamins and Other Metabolites.- D. Origins of Cellular Folates.- E. Transport Systems.- I. Selective Rescue.- F. Mechanism of Action of TMP/SMX.- I. Thymineless Death.- G. Summary.- References.- 2 Sulfonamides: Structure-Activity Relationships and Mechanism of Action.- A. Introduction.- B. Development of Sulfonamides and Sulfones.- I. Sulfonamides.- II. Sulfones.- III. Antimicrobial Spectrum.- C. Structure and Biological Activity.- I. Structure-Activity Relationship.- II. Physicochemical Properties and Antimicrobial Activity.- 1. Water Solubility.- 2. Lipid Solubility.- 3. Protein Binding.- III. Pharmacokinetics and Metabolism.- 1. Sulfonamides.- 2. Sulfones.- IV. Half-Life.- D. Mode of Antimicrobial Action.- I. Folic Acid Metabolism.- II. Action of Sulfonamides and Sulfones.- 1. Selectivity of Action.- III. Synergism with Dihydrofolate Reductase Inhibitors.- IV. Drug Resistance.- E. Present Status in Therapeutics.- References.- 3 Dihydrofolate Reductase.- A. Introduction.- B. Assay and Kinetic Studies.- C. Mechanism of Action.- D. Basis of Selectivity.- I. Kinetic Studies.- II. Inhibitor Binding Analysis.- III. Enzyme Conformation and Cooperativity.- IV Amino Acid Sequences.- V. Three-Dimensional Structures of DHFR.- E. Plasmid-Coded Reductases.- F. Genetics of DHFR.- References.- 4 Antibacterial Activity.- A. Introduction.- B. In Vitro Activity.- I. Effects of Medium and Size of Inoculum.- II. Bacteriostatic Activity.- III. Bactericidal Activity.- IV. Demonstration of Synergy.- C. Synergy and Sulfonamide-Resistant Strains.- D. Reversal of Activity of TMP.- E. Development of Resistance.- F. Spectrum of Activity of TMP/SMX.- G. Choice of Sulfonamide.- H. 2,4-Diaminopyrimidines as Single Agents.- J. Susceptibility Testing.- References.- 5 Selective Inhibitors of Bacterial Dihydrofolate Reductase: Structure-Activity Relationships.- A. Introduction.- B. Historical Perspective.- C. Some General Requirements for DHFR Inhibition and Antibacterial Activity.- D. Inhibitors of Specific DHFRs.- I. The 5-Phenyl Derivatives and Related Compounds.- II. 5-Benzyl-2,4-Diaminopyrimidines and Close Relatives.- 1. The 6-Unsubstituted Derivatives.- 2. 6-Substituted Derivatives.- 3. Substitution of a Heterocyclic Ring for the Benzene Moiety.- 4. Variations in the Bridge Between the Pyrimidine and Benzene Rings.- III. The 1,2-Dihydro-1,3,5-Triazines.- IV. Bicyclic Analogs of the Diaminopyrimidines.- E. Discussion.- F. Conclusion.- References.- 6 Kinetics of Antibacterial Effects.- A. Introduction: Bacterial Growth Kinetics in the Presence of Folate Inhibitors.- B. Sulfonamides (Synthetase Inhibitors).- I. Effect of Sulfonamides on Generation Rates of E. coli.- C. Trimethoprim (TMP): Dihydrofolate Reductase Inhibitor.- I. Effect of TMP on Generation Rates of E. coli.- II. Influence of TMP Concentration and Inoculum Size on the "Bactericidal"Trimethoprim/Sulfamethoxazole: An Overview.- A. Introduction.- B. Mechanisms of Action.- C. Resistance.- I. Chromosome-Mediated Resistance.- II. Plasmid-Mediated Resistance.- III. Thymidine Dependence.- D. Clinical Use of TMP/SMX.- I. Approved Indications in the United States.- II. Other Important Uses.- E. Use of TMP or SMX as Single Agents.- F. Adverse Effects.- G. Summary.- References.- Pharmacology and Biochemistry.- 1 Functions of Tetrahydrofolate and the Role of Dihydrofolate Reductase in Cellular Metabolism.- A. General.- B. Occurrence of Folates.- C. Functions of Tetrahydrofolate: Cofactors.- I. Formate and Equivalents.- 1. Purine Biosynthesis.- II. Formaldehyde Equivalents, Hydroxymethyl, and Methyl Derivatives.- 1. Methionine Biosynthesis.- 2. Thymidylate Synthesis.- 3. Vitamins and Other Metabolites.- D. Origins of Cellular Folates.- E. Transport Systems.- I. Selective Rescue.- F. Mechanism of Action of TMP/SMX.- I. Thymineless Death.- G. Summary.- References.- 2 Sulfonamides: Structure-Activity Relationships and Mechanism of Action.- A. Introduction.- B. Development of Sulfonamides and Sulfones.- I. Sulfonamides.- II. Sulfones.- III. Antimicrobial Spectrum.- C. Structure and Biological Activity.- I. Structure-Activity Relationship.- II. Physicochemical Properties and Antimicrobial Activity.- 1. Water Solubility.- 2. Lipid Solubility.- 3. Protein Binding.- III. Pharmacokinetics and Metabolism.- 1. Sulfonamides.- 2. Sulfones.- IV. Half-Life.- D. Mode of Antimicrobial Action.- I. Folic Acid Metabolism.- II. Action of Sulfonamides and Sulfones.- 1. Selectivity of Action.- III. Synergism with Dihydrofolate Reductase Inhibitors.- IV. Drug Resistance.- E. Present Status in Therapeutics.- References.- 3 Dihydrofolate Reductase.- A. Introduction.- B. Assay and Kinetic Studies.- C. Mechanism of Action.- D. Basis of Selectivity.- I. Kinetic Studies.- II. Inhibitor Binding Analysis.- III. Enzyme Conformation and Cooperativity.- IV Amino Acid Sequences.- V. Three-Dimensional Structures of DHFR.- E. Plasmid-Coded Reductases.- F. Genetics of DHFR.- References.- 4 Antibacterial Activity.- A. Introduction.- B. In Vitro Activity.- I. Effects of Medium and Size of Inoculum.- II. Bacteriostatic Activity.- III. Bactericidal Activity.- IV. Demonstration of Synergy.- C. Synergy and Sulfonamide-Resistant Strains.- D. Reversal of Activity of TMP.- E. Development of Resistance.- F. Spectrum of Activity of TMP/SMX.- G. Choice of Sulfonamide.- H. 2,4-Diaminopyrimidines as Single Agents.- J. Susceptibility Testing.- References.- 5 Selective Inhibitors of Bacterial Dihydrofolate Reductase: Structure-Activity Relationships.- A. Introduction.- B. Historical Perspective.- C. Some General Requirements for DHFR Inhibition and Antibacterial Activity.- D. Inhibitors of Specific DHFRs.- I. The 5-Phenyl Derivatives and Related Compounds.- II. 5-Benzyl-2,4-Diaminopyrimidines and Close Relatives.- 1. The 6-Unsubstituted Derivatives.- 2. 6-Substituted Derivatives.- 3. Substitution of a Heterocyclic Ring for the Benzene Moiety.- 4. Variations in the Bridge Between the Pyrimidine and Benzene Rings.- III. The 1,2-Dihydro-1,3,5-Triazines.- IV. Bicyclic Analogs of the Diaminopyrimidines.- E. Discussion.- F. Conclusion.- References.- 6 Kinetics of Antibacterial Effects.- A. Introduction: Bacterial Growth Kinetics in the Presence of Folate Inhibitors.- B. Sulfonamides (Synthetase Inhibitors).- I. Effect of Sulfonamides on Generation Rates of E. coli.- C. Trimethoprim (TMP): Dihydrofolate Reductase Inhibitor.- I. Effect of TMP on Generation Rates of E. coli.- II. Influence of TMP Concentration and Inoculum Size on the "Bactericidal"Trimethoprim/Sulfamethoxazole: An Overview.- A. Introduction.- B. Mechanisms of Action.- C. Resistance.- I. Chromosome-Mediated Resistance.- II. Plasmid-Mediated Resistance.- III. Thymidine Dependence.- D. Clinical Use of TMP/SMX.- I. Approved Indications in the United States.- II. Other Important Uses.- E. Use of TMP or SMX as Single Agents.- F. Adverse Effects.- G. Summary.- References.- Pharmacology and Biochemistry.- 1 Functions of Tetrahydrofolate and the Role of Dihydrofolate Reductase in Cellular Metabolism.- A. General.- B. Occurrence of Folates.- C. Functions of Tetrahydrofolate: Cofactors.- I. Formate and Equivalents.- 1. Purine Biosynthesis.- II. Formaldehyde Equivalents, Hydroxymethyl, and Methyl Derivatives.- 1. Methionine Biosynthesis.- 2. Thymidylate Synthesis.- 3. Vitamins and Other Metabolites.- D. Origins of Cellular Folates.- E. Transport Systems.- I. Selective Rescue.- F. Mechanism of Action of TMP/SMX.- I. Thymineless Death.- G. Summary.- References.- 2 Sulfonamides: Structure-Activity Relationships and Mechanism of Action.- A. Introduction.- B. Development of Sulfonamides and Sulfones.- I. Sulfonamides.- II. Sulfones.- III. Antimicrobial Spectrum.- C. Structure and Biological Activity.- I. Structure-Activity Relationship.- II. Physicochemical Properties and Antimicrobial Activity.- 1. Water Solubility.- 2. Lipid Solubility.- 3. Protein Binding.- III. Pharmacokinetics and Metabolism.- 1. Sulfonamides.- 2. Sulfones.- IV. Half-Life.- D. Mode of Antimicrobial Action.- I. Folic Acid Metabolism.- II. Action of Sulfonamides and Sulfones.- 1. Selectivity of Action.- III. Synergism with Dihydrofolate Reductase Inhibitors.- IV. Drug Resistance.- E. Present Status in Therapeutics.- References.- 3 Dihydrofolate Reductase.- A. Introduction.- B. Assay and Kinetic Studies.- C. Mechanism of Action.- D. Basis of Selectivity.- I. Kinetic Studies.- II. Inhibitor Binding Analysis.- III. Enzyme Conformation and Cooperativity.- IV Amino Acid Sequences.- V. Three-Dimensional Structures of DHFR.- E. Plasmid-Coded Reductases.- F. Genetics of DHFR.- References.- 4 Antibacterial Activity.- A. Introduction.- B. In Vitro Activity.- I. Effects of Medium and Size of Inoculum.- II. Bacteriostatic Activity.- III. Bactericidal Activity.- IV. Demonstration of Synergy.- C. Synergy and Sulfonamide-Resistant Strains.- D. Reversal of Activity of TMP.- E. Development of Resistance.- F. Spectrum of Activity of TMP/SMX.- G. Choice of Sulfonamide.- H. 2,4-Diaminopyrimidines as Single Agents.- J. Susceptibility Testing.- References.- 5 Selective Inhibitors of Bacterial Dihydrofolate Reductase: Structure-Activity Relationships.- A. Introduction.- B. Historical Perspective.- C. Some General Requirements for DHFR Inhibition and Antibacterial Activity.- D. Inhibitors of Specific DHFRs.- I. The 5-Phenyl Derivatives and Related Compounds.- II. 5-Benzyl-2,4-Diaminopyrimidines and Close Relatives.- 1. The 6-Unsubstituted Derivatives.- 2. 6-Substituted Derivatives.- 3. Substitution of a Heterocyclic Ring for the Benzene Moiety.- 4. Variations in the Bridge Between the Pyrimidine and Benzene Rings.- III. The 1,2-Dihydro-1,3,5-Triazines.- IV. Bicyclic Analogs of the Diaminopyrimidines.- E. Discussion.- F. Conclusion.- References.- 6 Kinetics of Antibacterial Effects.- A. Introduction: Bacterial Growth Kinetics in the Presence of Folate Inhibitors.- B. Sulfonamides (Synthetase Inhibitors).- I. Effect of Sulfonamides on Generation Rates of E. coli.- C. Trimethoprim (TMP): Dihydrofolate Reductase Inhibitor.- I. Effect of TMP on Generation Rates of E. coli.- II. Influence of TMP Concentration and Inoculum Size on the "Bactericidal" Effect of TMP.- III. Reversibility of TMP Action.- IV. Influence of Culture Broth Constituents on Biphasic Inhibition.- V. Development of Resistance Against Dihydrofolic Acid Reductase Inhibitors.- D. Combined Action of Sulfonamides and Trimethoprim (Folate Inhibitors).- I. Effect of TMP/SMX on Generation Rates of E. coli.- II. Influence of Inhibitory Power and Concentration of Sulfonamides or Sulfones on the Degree of Synergism.- III. Influence of Inhibitory Power of TMP Derivatives on the Degree of Synergism and Maximal Possible Effect.- IV. Selection Criteria for Combination of TMP and TMP Derivatives with Sulfonamides.- V. Mode of Action of Sulfonamides, TMP, and Their Combinations.- 1. Sulfonamides.- 2. TMP.- 3. Combinations of Sulfonamides and TMP.- References.- 7 Disposition and Metabolism of Trimethoprim, Tetroxoprim, Sulfamethoxazole, and Sulfadiazine.- A. Introduction.- B. Drug Disposition.- I. Drug Absorption.- II. Distribution into Biologic Fluids and Tissues.- 1. Physicochemical Properties that Influence Distributions..- 2. Relationship Between Plasma and Tissue Concentrations.- III. Excretion.- IV. Metabolism.- 1. Trimethoprim.- 2. Tetroxoprim.- 3. Sulfamethoxazole.- 4. Sulfadiazine.- C. Drug Assay Methods.- I. Trimethoprim and Related Benzylpyrimidines.- 1. Spectrofluorometric Methods.- 2. Quantitative Thin Layer Chromatography.- 3. High Pressure Liquid Chromatographic Methods.- 4. Gas-Liquid Chromatographic Analysis.- 5. Microbiologic Procedures.- 6. Other Methods.- II. Sulfonamides.- 1. Spectrophotometric Methods.- 2. Quantitative Thin Layer Chromatography.- 3. High Pressure Liquid Chromatography Methods.- D. Conclusion.- References.- 8 Preclinical Toxicity Testing of Co-trimoxazole and Other Trimethoprim/ Sulfonamide Combinations.- A. Introduction.- B. General Pharmacodynamic Actions.- I. Trimethoprim.- II. Trimethoprim and Sulfamoxole.- C. Acute Toxicity.- I. Trimethoprim, Sulfamethoxazole, and Co-trimoxazole.- II. Trimethoprim and Sulfamethoxypyridazine.- D. Subacute and Chronic Toxicity Tests.- I. Trimethoprim.- 1. Rats.- 2. Monkeys.- 3. Other Species.- II. Trimethoprim and Sulfamethoxazole.- 1. Rats.- 2. Rabbits.- 3. Monkeys.- E. Combinations of Trimethoprim and Other Sulfonamides.- I. Trimethoprim and Sulfafurazole.- II. Trimethoprim and Sulfadiazine.- III. Trimethoprim and Sulfamoxole.- IV. Trimethoprim and Sulfamethoxypyrazine.- F. Special Studies of the Thyroid and Trimethoprim/Sulfonamide Combinations.- G. Other Actions of Trimethoprim Alone or Combined with Sulfonamides.- I. Co-trimoxazole and Immunosuppression.- II. Local Effects of Intramuscular Injection of Trimethoprim and Various Sulfonamides.- III. Co-trimoxazole and Renal Failure.- H. Reproductive Toxicology.- I. Fetal Toxicity Tests.- 1. Rats.- 2. Rabbits.- II. Fertility Tests.- 1. Rats.- 2. Rabbits.- 3. Hamsters.- 4. Conclusions.- 5. Other Related Information.- III. Reproductive Toxicity of Trimethoprim Combined with Other Sulfonamides.- 1. Trimethoprim and Sulfamoxole.- 2. Trimethoprim and Sulfamethoxypyrazine J. Mutagenicity.- J. Mutagenicity.- I. Point Mutation Tests in Bacteria.- II. Human Cytogenetic Studies References.- References.- Clinical Pharmacology.- 9 Adverse Effect of Co-trimoxazole.- A. Introduction.- B. Gastrointestinal Disorders.- I. Upper Gastrointestinal Symptoms.- II. Lower Gastrointestinal Symptoms.- C. Skin Disorders.- I. Toxic Erythema.- II. Other Skin Reactions.- III. Sulfamethoxazole or Trimethoprim?.- D. Renal Disorders.- E. Haematological Disorders.- I. Folic Acid Deficiency.- II. Leucopenia/Agranulocytosis.- III. Thrombocytopenia.- IV. Haemolytic Anaemia.- F. Jaundice.- I. Liver Damage.- II. Hyperbilirubinaemia of the Newborn.- G. Pregnancy.- H. Miscellaneous.- J. Drug Interactions.- I. Pyrimethamine.- II. Azathioprine.- III. Warfarin.- IV. Phenytoin.- V. Hypoglycaemic Agents.- K. Conclusions.- References.- 10 Clinical Pharmacokinetics of Co-trimoxazole.- A. Introduction.- B. Absorption and Biologic Half-Lives.- C. Distribution.- I. Plasma.- II. Cerebrospinal Fluid.- III. Aqueous Humor.- IV. Breast Milk.- V. Prostatic and Seminal Material.- VI. Vaginal Fluid.- VII. Placental and Fetal Material.- VIII. Bile Fluid.- IX. Erythrocytes.- X. Bone.- XI. Other Tissues and Organs.- D. Metabolism.- E. Elimination.- F. Interactions.- References.- 11 Resistance: Genetics and Medical Implications.- A. Introduction.- B. Resistance to Sulfonamides.- I. Definition.- II. Natural Resistance.- III. Acquired Resistance.- C. Resistance to Trimethoprim.- I. Definition.- II. Natural Resistance.- III. Acquired Resistance.- D. Mechanisms of Acquired Resistance to Sulfonamides.- I. Results of Mutations.- 1. Decreased Permeability.- 2. Hyperproduction of p-Aminobenzoic Acid.- 3. Altered Dihydropteroate Synthase.- II. Acquisition of R Factors.- E. Mechanism of Acquired Resistance to Trimethoprim.- I. By Mutation.- 1. Thymineless Organisms.- 2. Modification of Dihydrofolate Reductase.- II. Plasmid-Mediated Resistance.- 1. Transferable.- 2. Nontransferable.- F. Medical Implications.- I. Sulfonamide-Resistant Strains.- II. Sulfonamide-Sensitive, Trimethoprim-Resistant Strains.- III. Emergence of Resistant Strains During Therapy.- G. Epidemiologic Overview of Resistance to Trimethoprim.- I. Gram-Positive Bacteria.- II. Gram-Negative Bacteria.- References.- Clinical Studies.- 12 Trimethoprim Alone: Clinical Uses.- A. Introduction.- B. Microbiologic and Pharmacokinetic Properties.- C. Relation of Sensitivities and Pharmacokinetics to Therapy of Urinary Tract Infections.- I. General.- II. Uncomplicated Urinary Tract Infections.- III. Complicated Urinary Tract Infections.- D. Prophylaxis.- I. Recurring Urinary Infection in Women and Children.- II. Immunosuppressed Patients.- E. Adverse Reactions and Safety.- I. General.- II. Dermatologic.- III. Gastrointestinal.- IV. Hematologic.- F. Bacterial Resistance.- I. General.- II. Finnish Experience.- III. Effect on Fecal Flora.- G. Conclusion.- References.- 13 Inhibitors of Dihydrofolate Reductase as Antiprotozoal Agents.- A. Introduction.- B. Points of Possible Therapeutic Attack.- C. Antimalarial Therapeutics.- I. Early Trials.- II. Clinical Cure with Pyrimethamine.- III. Causal Prophylaxis.- IV. Suppression and Mass Prophylaxis.- V. Gametocyticidal Effects.- VI. Radical Cure.- VII. Drug Resistance.- VIII. Combination with Sulfonamides and Sulfones.- 1. Suppressive and Clinical Cure.- 2. Effect on Other Sporozoa.- References.- 14 Pediatric Uses of Sulfonamides, Trimethoprim, and the Combination.- A. Introduction.- B. Hemophilus influenzae Infections.- I. Otitis Media.- 1. Acute.- 2. Serous and Chronic.- II. Sinusitis.- III. Prophylaxis to Prevent Secondary Infection.- C. Meningitis.- D. Urinary Tract Infections.- I. Acute.- II. Structural Defects of the Urinary System.- III. Prevention.- IV. Therapy of Periurethral and Rectal Flora.- V. Chlamydial Infections.- E. Pneumocystis carinii Pneumonia.- I. Therapy.- II. Prevention.- F. Enteric Diseases.- I. Salmonellosis.- II. Shigellosis.- III. Yersinia Infections.- 1. Acute Enteritis.- 2. Chronic Enteritis.- 3. Mesenteric Adenitis.- G. Miscellaneous Conditions.- I. Chronic Granulomatous Disease.- II. Osteomyelitis.- III. Ascending Cholangitis.- References.- 15 Use of Co-trimoxazole in Urinary Tract Infection.- A. Introduction.- B. Co-trimoxazole in Acute Urinary Tract Infection.- I. Epidemiology of Resistance.- 1. Types of Resistance.- II. Effects of Carriage Sites.- 1. Effect on Gut Flora.- 2. Effect on Urethral Colonisation.- III. Overtreatment.- C. Control of Recurrent Infection.- D. Role of the Combination.- I. Contrasting Effects of Trimethoprim and Sulfonamide in the Urine.- II. Toxicity.- References.- 16 Treatment of Genital Infections with Trimethoprim, Sulfonamides, and Combinations.- A. Introduction.- B. Treatment of Gonorrhea with Trimethoprim/Sulfamethoxazole.- I. Uncomplicated Anogenital Infection.- II. Rectal Infection.- III. Pharyngeal Infection.- IV. In Vitro Studies and Treatment of Gonorrhea with Trimethoprim/Sulfamethoxazole.- C. Infections Due to Chlamydia trachomatis.- I. Postgonococcal Urethritis.- II. Nongonococcal Urethritis.- III. Lymphogranuloma Venereum.- D. Chancroid.- E. Syphilis.- References.- 17 Treatment of Enteric Infections and Combinations.- A. Escherichia coli Diarrhea.- I. Introduction.- II. Trimethoprim/Sulfamethoxazole Treatment of E. coli Diarrhea.- 1. In Vitro Studies.- 2. Clinical Studies.- III. Summary.- B. Isospora belli Infections.- I. Introduction.- II. Trimethoprim/Sulfamethoxazole Treatment of an Isospora belli Infection.- C. Salmonella Infections.- I. Introduction.- 1. Typhoidal and Paratyphoidal Salmonella Infections.- 2. Non-Typhoidal Salmonella Infections.- II. Trimethoprim/Sulfamethoxazole in the Treatment of Salmonella typhi Infections.- 1. Therapeutic Studies in Antibiotic-Sensitive S. typhi Infections.- 2. Studies in Infections Due to Chloramphenicol-Resistant S. typhi Strains.- 3. Trimethoprim/Sulfamethoxazole Treatment of Typhoid Carriers.- 4. Adverse Effects.- 5. Summary.- III. Trimethoprim Alone in Treatment of Enteric Fever.- IV. Trimethoprim/Sulfamethoxazole Therapy in Non-Typhoidal Salmonellosis.- 1. In Vitro Studies.- 2. Clinical Studies.- 3. Summary.- D. Shigella.- I. Introduction.- II. Trimethoprim/Sulfamethoxazole Treatment in Shigellosis.- 1. In Vitro Studies.- 2. Clinical Studies.- 3. Summary.- E. Vibrio cholerae Infections.- I. Introduction.- II. Trimethoprim/Sulfamethoxazole Treatment in Cholera.- 1. In Vitro Studies.- 2. Clinical Studies.- 3. Summary.- F. Yersinia enterocolitica Infections.- I. Introduction.- II. Trimethoprim/Sulfamethoxazole and Yersinia enterocolitica.- 1. In Vitro Studies.- 2. Clinical Report.- 3. Summary.- References.- 18 Prostatitis.- A. Introduction.- B. Classification and Description of Patient Categories.- C. Acute and Chronic Bacterial Prostatitis.- I. Diagnosis.- II. Pathology.- III. Prostatic Immunoglobulins.- IV. The Antibacterial Factor in Prostatic Fluid.- V. Treatment.- D. Nonbacterial Prostatitis.- References.- 19 Co-trimoxazole in Chest Infections Including its Long-Term Use in Chest Disease.- A. Introduction.- B. Exacerbations of Chronic Bronchitis.- I. Levels of Two Components in Sputum.- II. Comparative Trials.- C. Other Acute Conditions.- I. Pneumocystis carinii Pneumonia.- D. Long-Term Treatment.- E. Parenteral TMP/SMX.- F. Alternative Drugs.- G. Trimethoprim Alone.- H. Future Developments.- References.- 20 Treatment of Miscellaneous and Unusual Infections with Trimethoprim and Trimethoprim/Sulfonamide Combinations.- A. Introduction.- B. Brucellosis.- C. Toxoplasmosis.- D. Nocardiosis.- E. Atypical Mycobacteria.- F. Mycoses.- I. Histoplasmosis.- II. Paracoccidioidomycosis.- III. Phycomycosis.- IV. Chromomycosis.- G. Pseudomonas Infections.- I. Pseudomonas pseudomallei.- II. Pseudomonas cepacia and Pseudomonas maltophilia.- H. Other Infections.- I. Bubonic Plague.- II. Rickettsiosis.- 1. Boutonneuse Fever.- 2. Q Fever.- III. Legionella pneumophila and Pittsburgh Pneumonia Agent Infections.- IV. Isospora belli Infections.- V. Malakoplakia.- VI. Pediculosis.- References.
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