Abstract & Commentary
ID Grand Rounds-Stanford University: Woman with Neutropenic fever, Ab Pain
By Susanna Tan, MD
Fellow, Division of Infectious Diseases, Stanford University
Dr. Tan reports no financial relationships in this field of study
Case History
A 44-year old woman with a history of acute myelogenous leukemia (AML) who recently completed a third-cycle of consolidation chemotherapy with idarubicin and cytarabine presented with fever and abdominal pain. Two days prior to admission, she developed mild, diffuse abdominal pain followed by fever and non-bloody vomiting. In the emergency department, she was found to be neutropenic, anemic, and thrombocytopenic. She was started on cefepime and given a unit of platelets. She was initially conversant, but then developed somnolence, hypotension, tachypnea, and hypoxia requiring intubation two hours after her initial presentation.
Past Medical History
She has a history of fibroids. She was diagnosed with AML five months prior to presentation and was currently in clinical and cytologic remission. Six weeks prior to presentation, she was hospitalized for neutropenic fever, typhlitis, bacteremia due to Klebisella pneumoniae and viridans streptococcus with a liver abscess and was treated with a four-week course of ceftriaxone and metronidazole. She was taking voriconazole for pulmonary nodules that were presumed to be fungal in etiology and she was also receiving acyclovir for prophylaxis.
Social History
She is originally from Eritrea and moved to the United States 20 years ago. She has not traveled outside the country in the past several years. She does not have pets. She works as an office assistant.
Physical Examination
Her temperature was 37.3C, blood pressure 126/61mmHg on norepinephrine and vasopresssin, heart rate 110 beats per minute, respiratory rate 35 beats per minute, oxygen saturation 90% on maximal vent settings. She was minimally responsive and intubated with frank blood within her endotracheal tube. Her sclera was icteric. She had bilateral coarse breath sounds. Her abdomen was distended, tympanic, and there were minimal bowel sounds. She had blood at the urethral meatus and within the foley catheter and there was mild bruising of her upper extremities bilaterally, but no petechiae or purpura. Several of her intravenous line sites were oozing blood.
Laboratory Results and Imaging
Repeat blood work done at the time of her clinical decline was significant for a white blood cell count of 0.1 cells/µL, hematocrit 12.0%, and platelets 226 cells/µL. She had a potassium of 6.6 mmol/L, bicarbonate 6 mmol/L, blood urea nitrogen 40 mg/dL, creatinine 1.4 mg/dL, anion gap 24, and lactate >15 mmol/L. Total bilirubin was 20.0mg/dL with a conjugated bilirubin of 1.7mg/dL, AST 1770 U/L, ALT 954 U/L. Uric acid was 7.9 mg/dL and LDH >4000 U/L. Her INR was 3.3, PTT 95 seconds, D-dimer >20K ng/mL, and fibrinogen 525 mg/dL. Respiratory virus PCR panel was negative. CT of the chest, abdomen, and pelvis showed extensive ground glass opacities and consolidative opacities throughout the lungs and extravasation of contrast into the third portion of the duodenum concerning for a gastrointestinal bleed. Uterine fibroids were stable compared to prior imaging.
Clinical Course
She was admitted to the intensive care unit. Meropenem, vancomycin, clindamycin, levofloxacin, osteltamivir, and liposomal amphotericin B were started at doses appropriately adjusted for hepatic and renal impairment. Acyclovir was continued.
She was also started on methylprednisolone sodium succinate 60mg IV Q6 hours because of concern for diffuse alveolar hemorrhage and received numerous units of packed red blood cell, platelet, and fresh frozen plasma products. Blood cultures were positive for Clostridium perfringens, Rothia mucilanginosa, Streptococcus equinus, Streptococcus gordonii, Enterococcus gallinarum, Herpes simplex virus, cytomegalovirus, and adenovirus PCR testing as well as galactomannan, strongyloides IgG antibody, and cryptococcus antigen tests were negative.
She developed worsening respiratory status with inability to adequately oxygenate and ventilate despite maximal ventilatory support and died 18 hours after initial presentation. Her family declined an autopsy.
Discussion
C. perfringens is an anaerobic, gram positive rod that is implicated in asymptomatic bacteremia, gastroenteritis, gas gangrene, shock and death. Septicemia with massive intravascular hemolysis is a rare but well-known complication, occurring in 7% to 15% of C. perfringens bacteremias. C. perfringens produces an alpha-toxin that damages red blood cell membranes by means of phospholipase activity, leading to spherocytosis and coombs-negative hemolysis. Peripheral smears classically demonstrate spherocytosis without schistocytes and may occasionally show ghost cells which are red blood cells that appear empty because they have a leaky membrane and no longer contain hemoglobin. C. perfringens can also produce streptolysin O and perfringolycin O toxins which have been implicated in the development of disseminated intravascular coagulation.
A review of 40 cases of C. perfringens septicemia with massive intravascular hemolysis found that most cases involved immunocompromised patients with underlying hematological disorders (22.5%), pancreatic or gastric cancer (12.5%) and/or diabetes (30.0%). The focus of infection was most commonly hepatobiliary (45.0%), intestinal or gynecological after invasive procedure.2 80% percent of cases did not survive. The median time between admission and death was only eight hours. In many cases, the patient had already gone into shock or died before a diagnosis could be made.2
A remarkably rapid deterioration’
Treatment involves the use of IV penicillin and removal of the focus of infection (i.e. by drainage of liver abscess, cholecystectomy, hysterectomy, or ERCP). One retrospective review found mortality benefit with the combination of clindamycin to penicillin.3
This patient presented with extensive intravascular hemolysis, sepsis, and DIC that is classic for C. perfringens. The etiology of the polymicrobial bacteremia is unclear, but was likely from an abdominal source. There was no obvious source that would have benefited from drainage. This case highlights the remarkably rapid deteriorationnd mortality that can be associated with C. perfringens septiciemia.
Diagnosis - Polymicrobial septicemia with extensive intra-vascular hemolysis due to C. perfringens.
REFERENCES
- Rechner PM. Clinical features of clostridial bacteremia: a review from a rural area. Clin Infect Dis 2001;33(3):349-53
- Van Bunderen CC, et al. Clostridium perfringens septicaemia with massive intravascular haemolysis: a case report and review of the literature. Neth J Med 2010;68(9):343-6.
- Simon TG, et al. Massive Intravascular Hemolysis From Clostridium perfringens Septicemia: A Review. J Intensive Care Med 2013;Sep 9.
