A 30-year-old man is brought to the emergency department due to high fever, chills, and rigors for 4 hours. He has no other symptoms. He was recently diagnosed with Hodgkin lymphoma and received his first cycle of chemotherapy 10 days ago. Temperature is 39.2 C (102.6 F), blood pressure is 90/40 mm Hg, pulse is 125/min, and respirations are 22/min. There is no evidence of skin rash or mucositis. The chest is clear to auscultation. The abdomen is soft and nontender. Perianal area is normal. Laboratory results are as follows:
| Hemoglobin | 11.1 g/dL |
| White blood cells | 700/mm3 with 20% neutrophils and 10% band forms |
| Platelets | 90,000/mm3 |
Chest radiograph is normal. Urinalysis is normal. Which of the following is the most likely cause of this patient's current condition?
This patient undergoing chemotherapy has neutropenic fever, defined as a temperature >38.3 C (>101 F) and an absolute neutrophil count <500/mm3 (eg, 700 leukocytes × [20% neutrophils +10% bands] = 210 neutrophils/mm3). Neutropenic fever without an identifiable source (eg, normal chest x-ray, normal urine culture, normal examination) is believed to be caused by translocation of endogenous bacteria into the bloodstream from mucositis, which results from chemotherapy-induced disruption of the gastrointestinal epithelium. Patients with severe neutropenia are at higher risk for overwhelming bacterial infection due to a blunted neutrophil-mediated inflammatory response.
This patient's very rapid onset (eg, 4 hours) of fever and signs of septic shock (eg, hypotension, tachycardia) is most consistent with a gram-negative bacterial infection (eg, Pseudomonas aeruginosa). Gram-negative infections are frequently identified as the causative pathogen of neutropenic fever and are associated with a rapid clinical deterioration due to the production of endotoxins, which stimulate the widespread release of proinflammatory mediators (eg, tumor necrosis factor) that results in hemodynamic decompensation. Gram-positive infections (eg, from indwelling catheters) also occur but tend to be less virulent with a slower onset and less severe course.
(Choice A) Latent viral infections are typically from the family Herpesviridae (eg, herpes simplex virus 1, varicella zoster virus) and can be a source of neutropenic fever. However, skin findings (eg, ulceration of the oral mucosa, disseminated vesicles in multiple dermatomes) are usually present.
(Choice B) Although anaerobic bacteria are part of the normal flora of the gastrointestinal tract, anaerobes are not typically identified as pathogens in patients with neutropenic fever unless the infection is polymicrobial (which is uncommon) or associated with abdominal surgery.
(Choice C) Disseminated tuberculosis can be a cause of fever in an immunocompromised patient, but weight loss, fatigue, respiratory symptoms, and abnormal chest x-ray are typically present. In addition, the presentation is usually subacute over days to weeks (vs 4 hours).
(Choice E) Invasive fungal infections can occur in neutropenic patients. However, they are typically slower growing (vs 4 hours) and are rarely the cause of an initial presentation of neutropenic fever. Instead, they are more commonly found in patients with persistent (eg, 7 days) or recurrent neutropenic fever who are at high risk (eg, increased number of chemotherapy cycles).
Educational objective:
Patients with neutropenic fever (ie, temperature >38.3 C [>101 F] and absolute neutrophil count <500/mm3) are at risk for overwhelming bacterial infections. The majority of severe infections that cause rapid clinical deterioration (eg, 4 hours) are caused by gram-negative organisms that produce endotoxins.