A 64-year-old woman comes to the emergency department with a 3-day history of intermittent fever, cough with blood-tinged sputum, night sweats, and generalized malaise. She also reports right-sided chest pain on deep inspiration over the last 24 hours. The patient was diagnosed with breast cancer and is undergoing combination chemotherapy. Her other medical problems include moderate chronic obstructive pulmonary disease and hypothyroidism.
Her temperature is 38.2 C (100.8 F), blood pressure is 107/64 mm Hg, pulse is 110/min, and respirations are 18/min. Pulse oximetry is 93% on room air. Physical examination is notable for pale conjunctiva. Lung examination shows scattered rhonchi, and cardiac examination is significant for tachycardia without murmurs. The abdomen is soft and nontender without organomegaly. There are no skin rashes.
Laboratory results are as follows:

The patient is started on vancomycin and piperacillin/tazobactam and fails to improve clinically after 3 days of treatment. Computed tomography scan of the chest shows several small (1-2 cm) nodular lesions scattered throughout the lung with surrounding ground-glass attenuation.
Blood and sputum cultures are negative, and bronchoscopy and bronchoalveolar lavage are performed for cultures and cytology.
Which of the following is the best next step in management of this patient?

Question

A 64-year-old woman comes to the emergency department with a 3-day history of intermittent fever, cough with blood-tinged sputum, night sweats, and generalized malaise.  She also reports right-sided chest pain on deep inspiration over the last 24 hours.  The patient was diagnosed with breast cancer and is undergoing combination chemotherapy.  Her other medical problems include moderate chronic obstructive pulmonary disease and hypothyroidism.
Her temperature is 38.2 C (100.8 F), blood pressure is 107/64 mm Hg, pulse is 110/min, and respirations are 18/min.  Pulse oximetry is 93% on room air.  Physical examination is notable for pale conjunctiva.  Lung examination shows scattered rhonchi, and cardiac examination is significant for tachycardia without murmurs.  The abdomen is soft and nontender without organomegaly.  There are no skin rashes.
Laboratory results are as follows:

The patient is started on vancomycin and piperacillin/tazobactam and fails to improve clinically after 3 days of treatment.  Computed tomography scan of the chest shows several small (1-2 cm) nodular lesions scattered throughout the lung with surrounding ground-glass attenuation.
Blood and sputum cultures are negative, and bronchoscopy and bronchoalveolar lavage are performed for cultures and cytology.
Which of the following is the best next step in management of this patient?

Quizplus · Accepted Answer

11ec193a_9862_502e_853d_d3eda0b2e11b_MD0002_00 This patient most likely has invasive pulmonary aspergillosis (IPA). Aspergillus has diverse presentations, including asymptomatic infection in immunocompetent hosts, allergic bronchopulmonary aspergillosis (ABPA) in patients with asthma or cystic fibrosis, and various patterns of chronic PA. Risk factors for chronic PA include prior lung disease such as pulmonary tuberculosis, ABPA, lung cancer, chronic obstructive pulmonary disease, and sarcoidosis. Symptoms of IPA are nonspecific and usually mimic bronchopneumonia: fever unresponsive to antibiotics, cough, sputum production, and dyspnea. Patients may also present with pleuritic chest pain (due to vascular invasion leading to thromboses that cause small pulmonary infarcts) and hemoptysis, which is usually mild. IPA is one of the most common causes of hemoptysis in neutropenic patients. Chest x-ray may not detect early-stage disease (ie, small nodules). Chest computed tomography (CT) scan shows single or multiple nodules with or without cavitations and "halo sign" (nodules surrounded by ground-glass infiltrates). Diagnosis is suggested by culture and histology. Enzyme-linked immunosorbent assay on serum or bronchoalveolar lavage fluid can be used to detect galactomannan antigen (present in Aspergillus cell walls), especially in patients with hematologic malignancies. Voriconazole has become the gold standard as primary therapy for invasive aspergillosis. Voriconazole was more effective than amphotericin B as initial therapy for IPA and was associated with significantly improved survival (71% vs 58%, respectively) in a randomized trial (Choice A). (Choice B) High-dose intravenous corticosteroids are not recommended for treating invasive aspergillosis due to the risk of further immunosuppression and worsening disease spread. Oral steroids are used in the treatment of ABPA. (Choice C) This patient's presentation (eg, severe neutropenia, chest CT scan with halo sign) is more suggestive of IPA than pulmonary tuberculosis. (Choice D) This patient has not shown clinical improvement with vancomycin and has negative bacterial cultures; linezolid is unlikely to be of much help. Educational objective: Invasive pulmonary aspergillosis occurs in severely immunocompromised patients. Diagnosis is made by chest computed tomography scan (nodules with or without cavitations surrounded by ground-glass infiltrates), culture, histopathology, or enzyme-linked immunosorbent assay for galactomannan antigen. Voriconazole is the preferred treatment. __________ References: Pulmonary aspergillosis: a clinical update. (http://www.ncbi.nlm.nih.gov/pubmed/17525130) Pulmonary aspergillosis: clinical presentation, diagnostic tests, management and complications. (http://www.ncbi.nlm.nih.gov/pubmed/20375786)

A 64-Year-Old Woman Comes to the Emergency Department with a 3-Day