Fulminant Clostridium perfringens Sepsis

Fulminant Clostridium perfringens sepsis is bacteraemia with this anaerobic Gram positive bacillus, causing massive intravascular haemolysis from alpha toxin (phospholipase C), shock, renal failure and DIC, with death often within hours. It is also called clostridial sepsis with intravascular haemolysis.

Epidemiology. It is rare. Bacteraemia occurs in about 1 in 100 to 1 in 1000 of anaerobic infections. Mortality exceeds 70 to 80% when haemolysis is present.

Causes and associations. Septic abortion and puerperal infection, biliary tract disease (cholangitis, cholecystitis), colonic malignancy, bowel ischaemia or perforation, necrotising pancreatitis, deep trauma and wound infection, injection related infection, immunosuppression, diabetes and haematological malignancy.

Pathophysiology. Alpha toxin hydrolyses red cell membrane phospholipids, causing haemolysis, and damages endothelium, platelets and myocardium. Theta toxin impairs host response. Haemolysis releases haemoglobin and potassium, producing renal tubular injury, hyperkalaemia and shock.

Presentation is sudden fever, rigors, severe abdominal, back or limb pain, vomiting, jaundice, dark red or brown urine, bronze or pale skin, hypotension, tachypnoea and confusion. Plasma may appear red or pink, and a blood sample may look haemolysed (gas bubbles in blood in some cases). Muscle involvement causes crepitus or gas gangrene.

Red flags.

• Intense haemolysis with jaundice and dark urine.
• Hypotension after uterine, biliary or bowel source.
• Potassium over 6.0 mmol/L or anuria.
• Rapid progression over hours.

Full blood count (falling haemoglobin, spherocytes, ghost cells), haptoglobin (low), lactate dehydrogenase, bilirubin, free haemoglobin, potassium, creatinine, creatine kinase, coagulation, fibrinogen, lactate, blood cultures (anaerobic bottles) and Gram stain, which shows large Gram positive rods. Do CT of the abdomen and pelvis to find the source (gas in tissues, abscess, perforation). Crossmatch can be difficult from haemolysis.

Differential diagnosis. Other haemolytic crises, incompatible transfusion, severe malaria, paroxysmal nocturnal haemoglobinuria, thrombotic microangiopathy, and sepsis from other organisms.

Antibiotics within 1 hour (combination).

• Benzylpenicillin 2.4 g (4 million units) IV every 4 hours, plus clindamycin 900 mg IV every 8 hours for toxin suppression.
• Add broad spectrum cover for polymicrobial infection: piperacillin-tazobactam 4.5 g IV every 6 hours or meropenem 1 g IV every 8 hours, with adjustment to renal function. Continue for at least 10 to 14 days and until source control is complete.

Source control (urgent). Evacuation of uterus and, if needed, hysterectomy; drainage or removal of gall bladder; resection of necrotic bowel; debridement of infected muscle. Do not delay surgery for stabilisation.

Resuscitation. Fluid, noradrenaline 0.05 to 1 microgram/kg/min, early ventilation, and renal replacement for hyperkalaemia, acidosis and renal failure.

Haemolysis. Transfuse red cells, but warmed units with matched cross-match, since haemolysis can interfere with testing. Consider red cell exchange transfusion or plasma exchange as salvage (limited evidence). Keep urine flowing to protect the kidney.

Hyperkalaemia. Calcium gluconate 10% 30 mL IV, insulin 10 units IV with glucose 25 g, salbutamol 10 to 20 mg nebulised and dialysis.

Coagulopathy. Plasma, cryoprecipitate and platelets for bleeding.

Hyperbaric oxygen. Used in some centres for gas gangrene, without proven benefit, and must not delay surgery or resuscitation.

Monitoring. Haemoglobin, potassium, creatinine, bilirubin, lactate, coagulation, urine colour and output every 2 to 4 hours.

Referral and escalation. Intensive care, surgery, infection specialists and nephrology at once.

Special groups. In septic abortion, involve obstetrics and gynaecology for evacuation. Counsel on the very high mortality early with the family.