Antitoxin treatment for liver abscess caused by Clostridium perfringens

We read with great interest the article ‘A case of emphysematous hepatitis with spontaneous pneumoperitoneum in a patient with hilar cholangiocarcinoma’ by Jung Ho Kim et al. The authors described fatal case of emphysematous hepatitis caused by C. perfringens , but did not mention the hemolysis or disseminated intravascular coagulopathy (DIC) during hospital course. Laboratory data on admission revealed anemia (hemoglobin 9.3 mg/dL), severely elevated aspartate transaminase (AST) level (882 IU/L), and high total bilirubin level (17.9 mg/dL), but alanine transaminase (ALT) level was elevated moderately (257 IU/ L). Although clinical data was limited, this disproportion between AST and ALT may suggest the intravascular haemolysis caused by C. perfringens. Van Bunderen et al retrospectively reviewed 40 cases of C. perfringens septicaemia that rapidly progressed to intravascular haemolysis and metabolic acidosis and led to death within a few hours after admission. The mortality rate was >80% despite treatments with high-dose intravenous penicillin and surgical debridement to eliminate the focus of infection. Therefore, we must redefine conventional treatments by reexamining the pathophysiology of such infections. Alpha toxin secreted by C. perfringens is responsible for intravascular haemolysis followed by severe anemia, acute renal failure, DIC and multi-organ failure. Therefore, specific antitoxic globulins (antitoxin) should be administered with antibiotics as early as possible to neutralise the toxin. In fact, the antitoxin against the alpha toxin of C. perfringens has been used for decades for the treatment for gas gangrene (myonecrosis) caused by C. perfringens. However, this product is no longer available in the United States because of poor efficacy and severe allergic reactions. Aggressive surgery, including amputation and repeated debridement, constitute the mainstay of treatment of myonecrosis caused by C. perfringens. On the other hand, the efficacy of antitoxin treatment for liver abscess caused by C. perfringens has not been evaluated. Unlike gas gangrene, C. perfringens septicaemia rapidly causes haemolysis followed by multi-organ failure; therefore, surgical intervention is not attempted in many cases. We recently introduced the use of the antitoxin against the C. perfringens alpha toxin to cease haemolysis and prevent multi-organ failure. Here we confirmed that the antitoxin effectively neutralises the alpha toxin secreted by C. perfringens; however, it does not possess antibacterial activity or the capacity to prevent bacterial growth and cannot restore organ function. Therefore, we propose that the optimal treatment for C. perfringens septicaemia should combine the antitoxin, antibiotics and surgical intervention.