The genus Clostridium encompasses more than 60 species that may be commensals of the gut microflora or may cause a variety of infections in humans and animals through the production of a plethora of proteinaceous exotoxins. C. tetani and C. botulinum, for example, cause specific clinical disease by elaborating single but highly potent toxins. In contrast, C. perfringens and C. septicum cause aggressive necrotizing infections that are attributable to multiple toxins, including bacterial proteases, phospholipases, and cytotoxins.
Vegetative cells of Clostridium species are pleomorphic, rod-shaped, and arranged singly or in short chains (Fig. 142-1); the cells have rounded or sometimes pointed ends. Although clostridia stain gram-positive in the early stages of growth, they may appear to be gram-negative or gram-variable later in the growth cycle or in infected tissue specimens. Most strains are motile by means of peritrichous flagella; C. septicum swarms on solid media. Nonmotile species include C. perfringens, C. ramosum, and C. innocuum. Most species are obligately anaerobic, although clostridial tolerance to oxygen varies widely; some species (e.g., C. septicum, C. tertium) will grow but will not sporulate in air.
Scanning electron micrograph of C. perfringens.
Clostridia produce more protein toxins than any other bacterial genus, and more than 25 clostridial toxins lethal to mice have been identified. These proteins include neurotoxins, enterotoxins, cytotoxins, collagenases, permeases, necrotizing toxins, lipases, lecithinases, hemolysins, proteinases, hyaluronidases, DNases, ADP-ribosyltransferases, and neuraminidases. Botulinum andtetanus neurotoxins are the most potent toxins known, with lethal doses of 0.2–10 ng/kg for humans. Epsilon toxin, a 33-kDa protein produced by C. perfringens types B and D, causes edema and hemorrhage in the brain, heart, spinal cord, and kidneys of animals. It is among the most lethal of the clostridial toxins and is considered a potential agent of bioterrorism (Chap. 221). The genomic sequences of some pathogenic clostridia are now available and are likely to facilitate a comprehensive approach to understanding the virulence factors involved in clostridial pathogenesis.
Clostridium species are widespread in nature, forming endospores that are commonly found in soil, feces, sewage, and marine sediments. The ecology of C. perfringens in soil is greatly influenced by the degree and duration of animal husbandry in a given location and is relevant to the incidence of gas gangrene caused by contamination of war wounds with soil. For example, the incidence of clostridial gas gangrene is higher in agricultural regions of Europe than in the Sahara Desert of Africa. Similarly, the incidences of tetanus and food-borne botulism are clearly related to the presence of clostridial spores in soil, water, and many foods. Clostridia are present in large numbers in the indigenous microbiota of the intestinal tract of humans and animals, in the female genital tract, and on the oral mucosa. It should be noted that not all commensal clostridia are toxigenic.
Clostridial infections remain a serious public health concern worldwide. In developing nations, food poisoning, necrotizing enterocolitis, and gas gangrene are common because large portions of the population are poor and have little or no immediate access to health care. These infections remain prevalent in developed countries as well. Gas gangrene commonly follows knife or gunshot wounds or vehicular accidents or develops as a complication of surgery or gastrointestinal carcinoma. Severe clostridial infections have emerged as a health threat to injection drug users and to women undergoing childbirth or abortion. Historically, clostridial gas gangrene has been the scourge of the battlefield. The global political situation portends another possible scenario involving mass casualties of war or terrorism, with extensive injuries conducive to gas gangrene. Thus there is an ongoing need to develop novel strategies to prevent or attenuate the course of clostridial infections in both civilians and military personnel. Vaccination against exotoxins important in pathogenesis would be of great benefit in developing nations and could also be used safely in at-risk populations such as the elderly, patients with diabetes who may require lower-limb surgery due to trauma or poor circulation, and those undergoing intestinal surgery. Moreover, a hyperimmune globulin would be a valuable tool for prophylaxis in victims of acute traumatic injury or for attenuation of the spread of infection in patients with established gas gangrene.
Life-threatening clostridial infections range from intoxications (e.g., food poisoning, tetanus) to necrotizing enteritis/colitis, bacteremia, myonecrosis, and toxic shock syndrome (TSS). Tetanus and botulism are discussed in Chaps. 140 and 141, respectively. Colitis due to C. difficile is discussed in Chap. 129.
Clostridial Wound Contamination
Of open traumatic wounds, 30–80% are reportedly contaminated with clostridial species. In the absence of devitalized tissue, the presence of clostridia does not necessarily lead to infection. In traumatic injuries, clostridia are isolated with equal frequency from both suppurative and well-healing wounds. Thus, diagnosis and treatment of clostridial infection should be based on clinical signs and symptoms and not solely on bacteriologic findings.
Polymicrobial Infections Involving Clostridia
Clostridial species may be found in polymicrobial infections also involving microbial components of the indigenous flora. In these infections, clostridia often appear in association with non-spore-forming anaerobes and facultative or aerobic organisms. Head and neck infections, conjunctivitis, brain abscess, sinusitis, otitis, aspiration pneumonia, lung abscess, pleural empyema, cholecystitis, septic arthritis, and bone infections all may involve clostridia. These conditions are often associated with severe local inflammation but may lack the characteristic systemic signs of toxicity and rapid progression seen in other clostridial infections. In addition, clostridia are isolated from ∼66% of intraabdominal infections in which the mucosal integrity of the bowel or respiratory system has been compromised. In this setting, C. ramosum, C. perfringens, and C. bifermentans are the most commonly isolated species. Their presence does not invariably lead to a poor outcome. Clostridia have been isolated from suppurative ...