A 26-year-old man undergoing chemotherapy for metastatic seminoma comes to the emergency department with fever and chills for the last 24 hours. He has no chest pain, shortness of breath, cough, abdominal pain, diarrhea, or skin rash. His temperature is 38.9 C (102 F), blood pressure is 118/70 mm Hg, pulse is 102/min, and respirations are 18/min. Examination shows mucosal pallor. There is mild gingival erythema but no evidence of bleeding. The cardiopulmonary examination is normal. The abdomen is soft and nontender to palpation. The perianal area is without lesions. Laboratory results are as follows: Chest x-ray shows no infiltrates. Urinalysis is normal. The patient is admitted to the hospital. Which of the following is the most appropriate initial therapy for this patient?

Question

A 26-year-old man undergoing chemotherapy for metastatic seminoma comes to the emergency department with fever and chills for the last 24 hours.  He has no chest pain, shortness of breath, cough, abdominal pain, diarrhea, or skin rash.  His temperature is 38.9 C (102 F), blood pressure is 118/70 mm Hg, pulse is 102/min, and respirations are 18/min.  Examination shows mucosal pallor.  There is mild gingival erythema but no evidence of bleeding.  The cardiopulmonary examination is normal.  The abdomen is soft and nontender to palpation.  The perianal area is without lesions.  Laboratory results are as follows:  Chest x-ray shows no infiltrates.  Urinalysis is normal.  The patient is admitted to the hospital.  Which of the following is the most appropriate initial therapy for this patient?

Quizplus · Accepted Answer

This patient is febrile with no obvious focus of infection given the normal chest x-ray and urinalysis. He has febrile neutropenia (FN). Neutropenia is defined as an absolute neutrophil count (ANC) <1500 neutrophils/mm³ (severe neutropenia is ANC <500 neutrophils/mm³). Patients with ANC <1000 neutrophils/mm³ (as in this patient with ANC = 690 leukocytes × 20% neutrophils = 138 neutrophils/mm³) are at higher risk for overwhelming bacterial infection due to an absent or blunted neutrophil-mediated inflammatory response. Chemotherapy may also lead to disruption of the skin and mucosal barrier of the mouth and gastrointestinal tract, resulting in mucositis and subsequent translocation of the bacteria into the bloodstream. Gram-negative organisms, particularly Pseudomonas aeruginosa, are frequently identified and cause severe infection; gram-positive bacteria are also commonly identified in bloodstream infections. FN is a medical emergency, and starting early empiric antibiotic therapy can avoid progression of infection to severe sepsis and life-threatening complications. Initial evaluation includes blood and urine cultures, followed by immediate intravenous broad-spectrum antibiotics. Monotherapy with an antipseudomonal beta-lactam agent (eg, cefepime, meropenem, piperacillin-tazobactam) provides both gram-negative and gram-positive coverage and is recommended initially. (Choice A) Herpes virus infections are not a typical cause of FN, and empiric acyclovir therapy is not recommended unless the patient has clinical signs consistent with a herpes infection. (Choices B and D) Ceftriaxone and linezolid do not have antipseudomonal coverage and are not recommended as initial empiric antibiotics. (Choice C) Although ciprofloxacin has reasonable activity against Pseudomonas, it does not have good activity against anaerobes. It may be used in combination with a beta-lactam/beta-lactamase agent (eg, amoxicillin-clavulanic acid) for outpatient therapy of low-risk neutropenic patients. (Choice F) Vancomycin has no gram-negative activity. Although gram-positive bacteria are commonly identified in bloodstream infections of patients with FN, routinely adding vancomycin for all patients with FN was not associated with improved clinical outcomes and resulted in more toxicity. Vancomycin is added to empiric drug therapy for patients with known colonization with methicillin-resistant Staphylococcus aureus, probable catheter-related infection, skin/soft-tissue infection, pneumonia, or hemodynamic instability. (Choice G) Antifungal medications are recommended in high-risk neutropenic patients with persistent fever after 4-7 days of initial therapy in whom a source of infection is not identified. Educational objective: Patients with febrile neutropenia should be started on empiric broad-spectrum antibiotics as soon as possible after blood cultures are obtained. Empiric monotherapy with an antipseudomonal agent (eg, cefepime, meropenem, piperacillin-tazobactam) is recommended for initial management. References: Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. (http://www.ncbi.nlm.nih.gov/pubmed/21258094) Evidence-based approach to treatment of febrile neutropenia in hematologic malignancies (http://www.ncbi.nlm.nih.gov/pubmed/24319213)

A 26-Year-Old Man Undergoing Chemotherapy for Metastatic Seminoma Comes to the Emergency