Other Clostridium Species

Histotoxic Infections

Table 191.1 shows characteristics of histotoxic infections, and the likely responsible Clostridium spp. C. perfringens is the most common pathogen associated with gas gangrene. Other responsible organisms that can also produce exotoxins and cause gas gangrene are C. bifermentans , C. sordellii , C. septicum , C. novyi , and C. histolyticum . The spectrum of infection includes cellulitis, necrotizing fasciitis, and severe myonecrosis (gas gangrene). Severe myonecrosis often is a polymicrobial infection that occurs after bacteremic spread from an intestinal site of colonization to traumatized soft tissue.

In adults, the predisposing factor for BSI often is colorectal or hematologic malignant disease, inflammatory bowel disease, or hemodialysis. ^, C. septicum BSI can signal the presence of an underlying intestinal malignancy. Trauma to the colon or female genital tract or injection drug abuse is present in most patients with BSIs. C. sordellii and C. septicum deserve special note because of the generally rapidly fatal course of infection. C. septicum septicemia in children usually is associated with profound neutropenia (as a primary genetic disorder or related to malignant disease or chemotherapy). Typhlitis, mucositis, or necrotizing enterocolitis frequently is present, but some cases occur spontaneously. In such cases, BSI and generalized soft tissue infection progress rapidly, and gas production is evident clinically at widely distributed body sites ( Fig. 191.1A ). Survival is unusual. C. septicum septicemia and secondary brain abscess can complicate hemolytic uremic syndrome caused by Escherichia coli O157:H7, ^, bowel ischemia, or trauma, and the combination often is fatal. C. sordellii infections occur in previously healthy people following induced or spontaneous abortion, childbirth, genital tract operations, skin or soft tissue trauma, or injection drug abuse. Lethal and hemorrhage toxins are thought to be responsible for typical leukemoid reactions and high fatality rates. Clostridial endocarditis is rare. Clostridial bacteremia can be transient, without clinical consequence, or it can represent a contamination. In infants, BSI can be associated with necrotizing enterocolitis.

Gas gangrene affects muscle tissue that has been compromised by surgical procedures, trauma, or vascular insufficiency and when it has been contaminated with C. perfringens spores, usually from foreign material, such as clothing, dirt, or a medical device. The ubiquitous nature of C. perfringens spores in dirt, soil, and clothing and on skin, especially of the lower trunk, provides multiple opportunities for inoculation of wounds. The metabolic requirements of C. perfringens for growth are the major factors in the establishment of clostridial myonecrosis.

After inoculation and outgrowth of C . perfringens in the muscle, severe, rapidly progressive myonecrosis results from toxins elaborated, principally the α-toxin. The α-toxin is a lecithinase that rapidly lyses cell membranes and causes hemolysis, myofibrillar injury, and vascular permeability. Severe systemic manifestations accompany local infection and may be toxin related. The patient has fever, tachycardia, and diaphoresis and is alert, anxious, and apprehensive or apathetic. Shock and attendant multiorgan failure ensue in most cases.

Gas gangrene characteristically begins 1–4 days (range, 6 hours to 21 days) after an injury. The onset is heralded by sudden and persistent pain at the site of injury and an accompanying limb “heaviness.” Overlying skin appears normal at the onset but quickly becomes cool, pale, and waxy as a result of ischemia. Local tense swelling, tenderness, pallor, and a thin hemorrhagic exudate are noted first; pallor gives way to a bronze or magenta discoloration, and hemorrhagic (purplish) bullae appear. Pain remains the most prominent symptom. Soft tissue crepitation can be present, but if the amount of gas is small, this finding may not be noted by physical examination, ultrasound, or radiographic evaluation. As the condition worsens, a peculiar offensive odor (sometimes described as sweet) is noted, and a brown serosanguineous discharge is present. Gram stain of discharge shows large numbers of gram-positive bacilli with few or no white blood cells. Involved muscle can be edematous and pale initially, advancing to a mottled appearance and greenish black gangrene. Consistency of the muscle changes from pasty and mucoid to friable and liquefied.

Tachycardia, widespread myalgia, anxiety, and diaphoresis despite low-grade fever appear early and progress rapidly to hypotension, poor perfusion, disseminated intravascular coagulation, and mental status changes. ^, Without definitive therapy, the disease progresses inexorably, with high fever (often with rigors), shock, renal failure, metabolic acidosis, and coma, to death. Clostridial septicemia can occur terminally.

Food Poisoning

Acute self-limiting gastroenteritis caused by contaminated food products (mostly meat products) often is associated with C. perfringens and its toxins. C. perfringens has been documented as the third most common cause of outbreaks of foodborne disease (after Salmonella and Staphylococcus aureus ). Food poisoning occurs as a result of ingestion of vegetative forms of C. perfringens that develop in foods standing at a temperature between 30°C–50°C. Primary contamination of meat with C. perfringens spores is common. The temperature of cooking meat must exceed 120°C to ensure that spores are killed. With cooking at lower temperatures, spores can be converted to vegetative forms during cooling of food, thus risking the growth of C. perfringens in the gastrointestinal tract.

Although the symptoms of C. perfringens food poisoning are attributable largely to the action of enterotoxins, these enterotoxins usually are formed in the gut after ingestion of the organisms. Ingestion of preformed toxin results only in diarrhea if gastric acidity has been neutralized. The enterotoxin formed in vivo is a 35-kd polypeptide that is heat and acid labile and is inactivated by some proteolytic enzymes. The enterotoxin gene cpe can be used to detect illness-causing strains. The toxin inhibits absorption of glucose and secretion of water, sodium, and chloride, and it strips the epithelium of villous tips. The in vitro cytotoxic effect is similar to that of Shigella toxin but differs from that of cholera or E. coli enterotoxins. Adenyl cyclase appears not to be involved in the mediation of C. perfringens toxin activity. The resultant gastroenteritis has components of secretory and inflammatory diarrhea.

C. perfringens food poisoning is an acute, self-limiting diarrheal illness with an onset 6–24 hours after consumption of contaminated food. Crampy abdominal pain commonly accompanies watery diarrhea, which does not contain blood or mucus. Fever, nausea, and vomiting occur rarely. The duration of disease is commonly <24 hours, and medical intervention usually is not warranted or sought, except in the case of outbreaks. Making the distinction between food poisoning caused by C. perfringens and that caused by Bacillus cereus is difficult.

Differentiating this acute diarrheal disease from the numerous other viral, bacterial, and toxic causes of diarrhea on clinical grounds can be difficult unless an outbreak has occurred. The absence of fever, nausea, vomiting, and blood or mucus in stools in a patient with C. perfringens diarrhea makes Salmonella , Shigella , Campylobacter , Yersinia , and rotavirus infection unlikely. The duration of infection caused by these pathogens usually is more prolonged than C. perfringens food poisoning. The diagnosis can be confirmed only by isolation of large quantities of C. perfringens from the suspect food (>10 ⁶ colony-forming units/g) and the patient’s fecal samples. The enterotoxin can be detected using a cytopathic toxin neutralization assay, latex agglutination, or enzyme immunoassays. However, this approach is not useful in clinical diagnosis.