Microbiology and Pathogenesis

Clostridia are pleomorphic, gram-positive, spore-forming organisms. Most species are obligate anaerobes; some (e.g., C. septicum, C. tertium) can grow-but not sporulate-in air.

• In humans, clostridia reside in the GI and female genital tracts and on the oral mucosa.
• Clostridial species produce more protein toxins than any other bacterial genus; the C. perfringens epsilon toxin is among the most lethal and is considered a potential agent of bioterrorism.

Epidemiology and Clinical Manifestations

Life-threatening clostridial infections range from intoxications (e.g., food poisoning, tetanus) to necrotizing enteritis/colitis, bacteremia, myonecrosis, and toxic shock syndrome (TSS).

• Clostridial wound contamination: Of open traumatic wounds, 30-80% are contaminated with clostridial species. Diagnosis and treatment of clostridial infection should be based on clinical signs and symptoms, given that clostridia are isolated with equal frequency from both suppurative and well-healing wounds.
• Polymicrobial infections involving clostridia: Clostridial species can be involved in infection throughout the body; 66% of intraabdominal infections related to compromised mucosal integrity involve clostridia (most commonly C. ramosum, C. perfringens, and C. bifermentans).
• Enteric clostridial infections: Disease ranges from food-borne illnesses and antibiotic-associated colitis (Chap. 85 Infectious Diarrheas and Bacterial Food Poisoning) to extensive necrosis of the intestine (e.g., enteritis necroticans and necrotizing enterocolitis, which are due to toxigenic C. perfringens type C and type A, respectively).
• Clostridial bacteremia: C. perfringens causes 79% of clostridial bacteremias; when associated with myonecrosis, clostridial bacteremia has a grave prognosis.
  • - C. septicum is also commonly associated with bacteremia (<5% of cases). More than 50% of pts with C. septicum bacteremia have a GI anomaly or an underlying malignancy. Neutropenia (of any origin) is also associated with C. septicum bacteremia.
    • Pts with clostridial bacteremia-particularly that due to C. septicum-require immediate treatment, as infection can metastasize and cause spontaneous myonecrosis.
• Clostridial skin and soft-tissue infections: Necrotizing clostridial soft-tissue infections are rapidly progressive and are characterized by marked tissue destruction, gas in the tissues, and shock. Most pts develop severe pain, crepitus, brawny induration with rapid progression to skin sloughing, violaceous bullae, and marked tachycardia.
  • - C. perfringens myonecrosis (gas gangrene) is accompanied by bacteremia, hypotension, and multiorgan failure and is invariably fatal if untreated.
    • If due to trauma, gas gangrene has an incubation period of 6 h to <4 days. Disease initially presents as excruciating pain at the affected site and the development of a foul-smelling wound containing a thin serosanguineous discharge and gas bubbles.
    • Spontaneous gas gangrene results from hematogenous seeding of normal muscle with toxigenic clostridia from a GI source. Confusion, extreme pain in the absence of trauma, and fever should heighten suspicion.
  • - TSS: Endometrial clostridial infection (particularly with C. sordellii) is usually related to pregnancy or gynecologic procedures and proceeds rapidly to TSS and death.
    • Systemic manifestations, including edema, effusions, profound leukocytosis (50,000-200,000/µL), and hemoconcentration (Hct of 75-80%), are followed by the rapid onset of hypotension and multiple-organ failure.
    • Fever is usually absent.
  • Other clostridial skin and soft-tissue infections include crepitant cellulitis (involving SC or retroperitoneal tissues in diabetic pts), cellulitis and abscess formation due to C. histolyticum, and endophthalmitis due to C. sordellii or C. perfringens.

Diagnosis

Isolation of clostridia from clinical sites does not in itself indicate severe disease. Clinical findings and presentation must also be taken into account.