ABSTRACT
I. INTRODUCTION 328 II. HISTORICAL PERSPECTIVES 328
III. CLINICAL CONSIDERATIONS 329 A. Overview 329 B. Acquisition of Clostridium difficile 330 C. Disease Manifestations 332 D. Diagnosis 332 E. Pathology 333 F. Treatment 333 G. Recurrent Disease 334 H. Prevention 335
IV. CLOSTRIDIUM DIFFICILE TOXINS 335 A. Overview 335 B. Factors Affecting Toxin Production 336 c. Experimental Production and Purification of C. difficile Toxins 337 D. Physical and Chemical Characteristics of Toxins A and B 338 E. Immunocharacterization of Toxins A and B 339 F. Effects of Toxins on Cultured Cells 340 G. Biological Activity of C. difficile Toxins 346 H. Interactions with the Immune System 349 I. The Role of Inflammatory Mediators 351 J. Genetics of C. difficile Toxins 351
v. ADDITIONAL VIRULENCE FACTORS 352 VI. CONCLUSION 353
REFERENCES 353
I. INTRODUCTION
ClostridiumdifficileandItsToxins329
(1974)described"clindamycincolitis."Inthisprospectivestudyof200patientstreated withclindamycin,42(21%)developeddiarrhea,and20(10%)hadpseudomembranous colitisbyproctoscopicexamination;therewaslittletosuggestanunderlyingbacterial causeforthisdisease(Tedescoetal.,1974).
