Hemolysis with signs of septic shock due to C perfringens infection has been almost invariably fatal in several small case series reviews.2,3 While definitive identification of C perfringens is often delayed, it may be identified on gram stain; a DNA polymerase chain reaction (PCR) test has been developed, but is not widely available.6
The deceptive severity of this patient’s illness is a hallmark of C perfringens sepsis. Many patients may appear calm and report they feel “fine.” This lack of concern, “la belle indifférence,” is also seen in patients with necrotizing soft-tissue infections.7
Patients may be hemodynamically normal or fail to meet SIRS criteria. Case series have revealed no difference in SIRS criteria between survivors and nonsurvivors of C perfringens septicemia2; however, survivors were observed to have higher plasma fibrinogen levels than nonsurvivors.2 Fibrinogen, which is a known risk factor for the development of shock,8 may be a useful prognostic indicator given the association between shock and death in C perfringens septicemia.2
These factors were evident in this case. During the first 5 hours in the ED, the patient was hemodynamically normal, meeting only one of the SIRS criteria (elevated WBC). He also exhibited a nonchalant attitude, saying he “felt fine” before his rapid decline and death. Although fibrinogen was not available, this case is a clear reminder that exclusive use of SIRS criteria and patient reporting as barometers for severity of illness can be misleading.
Treatment
First-line treatment for C Perfringens includes high-dose IV penicillin G (10-24 million units daily), clindamycin for suppression of toxin synthesis, and surgical debridement.1,10 Second-line antibiotics include penicillin derivatives, chloramphenicol, doxycycline, carbapenems, tetracycline, and metronidazole.10,11
Immediate surgical intervention may be needed for survival. Limited review studies from Tokyo and the Netherlands indicate that surgical intervention is a strong prognostic indicator of survival and should be pursued expediently.2,3 A Dutch review 3 of 40 cases in the English medical literature published since 1990 demonstrated an overall mortality rate of 80% (32 of 40 patients). Among eight patients who had a surgical intervention (eg, hysterectomy, drainage of liver abscess) two deaths (25%) occurred. Those patients medically managed had a mortality rate of 93.7% (30/32 patients). While there is an impressive difference between these two groups—the authors assert a relative risk of mortality with surgical intervention of 0.27 (95% CI 0.08 to 0.89)—they are incomparable as many individuals in the medically managed group were not candidates for surgical intervention due to multiorgan failure or death prior to diagnosis.
While the strength of evidence for the efficacy of other interventions is limited, observational data suggest novel interventions are worth considering in an attempt to save these patients. Hyperbaric oxygen therapy has been used with some success in combination with surgery for gas gangrene and necrotizing soft-tissue infections; a few observational studies have shown benefit in sepsis.11 In the setting of massive hemolysis, blood transfusion may be required.12 If hemolysis is caught in early stages, exchange transfusion may prevent further complications.13 The α-toxin antitoxin, historically used for gas gangrene, has been abandoned in the United States due to severe allergic reactions and poor efficacy.14 However, researchers in Japan are investigating the efficacy of antitoxin for C perfringens liver abscesses when multiorgan failure prohibits surgical intervention.15
Conclusion
C perfringens septicemia should be considered when intravascular hemolysis is encountered, even in patients not meeting SIRS criteria. Treatment with appropriate antibiotics and an expedited search for a source (with subsequent immediate intervention) must be initiated prior to onset of shock if there is any hope of survival. If C perfringens septicemia is suspected, clear communication with family members and consultants about the seriousness of the patient’s condition is of the upmost importance as all parties involved must be made aware of the aggressive and unrelenting course of this disease and high likelihood of death.
Dr Samuels is a third-year resident in the department of emergency medicine at Brown University, Providence, Rhode Island. Dr Hack is the division director of medical toxicology at the University of Emergency Medicine Foundation; director of the educational program in medical toxicology and an associate professor at Warren Alpert Medical School; and an attending physician in the department of emergency medicine at Brown University, Rhode Island Hospital, Miriam Hospital, Providence.