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January 20, 2015 Issue

Clinical Practice Points

Patient Care
Medical Knowledge

Combination Antifungal therapy for Invasive Aspergillosis: A Randomized Trial

This trial compared combination voriconazole and anidulafungin with voriconazole monotherapy for treatment of invasive aspergillosis (IA). Although overall mortality and safety were not different, mortality was lower with combination therapy in a subgroup of patients whose IA diagnosis was established by radiographic findings and galactomannan positivity. In the absence of definitive trial results, clinicians may decide to choose therapy for IA on the basis of individual patient characteristics.

Use this article to:

  • Start a teaching session with a multiple-choice question. We’ve provided one below.
  • Present the history and radiographic studies of a patient (or patients) with invasive aspergillosis. You might ask your hematology or infectious disease services to help you identify some. Ask a radiologist to review the salient features of the imaging studies with your team.
  • Ask who is at risk for invasive aspergillosis. How are they treated? How do azole and echinocandin antifungals work? What are the major considerations and potential problems with their use? What are the alternatives?
  • This study was limited by a mortality rate that was different than expected, thus limiting power. Ask what “power” means in a clinical study. What factors limit power, and how did it happen here? Consider inviting an epidemiologist to help lead the discussion.

Patient Care
Interpersonal and Communication Skills

Factors Associated With Lack of Viral Suppression at Delivery Among Highly Active Antiretroviral Therapy–Naive Women With HIV: A Cohort Study

Highly active antiretroviral therapy (HAART) that suppresses viral replication decreases the risk for maternal-to-child transmission of HIV at delivery. This study found that the timing of HAART initiation and prenatal care, as well as medication adherence during pregnancy, were associated with detectable viral load at delivery.

Use this study to:

  • Ask your learners what issues need to be considered when caring for a pregnant woman with HIV infection. What organ systems might be affected? What symptoms should they ask about? What are key elements of the physical examination? Use the information, including tables, in ACP Smart Medicine: HIV in Pregnancy to prepare a teaching session.
  • Ask how HAART should be used in pregnancy. Which drugs? When should they be initiated?
  • Discuss whether we can compel a pregnant woman to take medication for the health of her child even if she does not want to do so. Ask your learners how they would approach a conversation with such a patient.

Patient Care

Overuse of Testing in Preoperative Evaluation and Syncope: A Survey of Hospitalists

Unnecessary testing wastes limited resources and may expose patients to harm. Physicians responding to this survey reported substantial overuse of testing despite clinical guidelines and evidence, often motivated by a desire to provide reassurance to patients, family members, or themselves.

Use this study to:

  • Ask your learners to generate a differential diagnosis of syncope. What are the features of neurocardiogenic syncope?
  • What studies should be ordered in which patients? Do all patients with syncope require an ECG? An echo? Which ones require neurologic testing?
  • Use ACP Smart Medicine: Syncope for tables to review these issues. Review the algorithm provided in the “Figures” section, and ask your learners if they agree.

Medical Knowledge

Acute Vasodilator Responsiveness and Microvascular Recruitment in Idiopathic Pulmonary Arterial Hypertension

This clinical observation presents evidence that acute vasodilator responsiveness might differentiate vasoconstriction from irreversible vascular obliteration in patients with pulmonary arterial hypertension (PAH).

Use this study to:

  • Ask what the differential diagnosis is of pulmonary hypertension (PH). Why is it so important to distinguish PAH from other, more common, causes of PH? What are they? Can an echo differentiate between them? How are they treated? Use In the Clinic: Pulmonary Hypertension to answer these questions.
  • Review how a right heart catheterization is performed, what parameters are assessed, and what they mean. Ask someone who specializes in the care of these patients to review the hemodynamic findings of patients with pulmonary venous hypertension and PAH.
  • How does this small study help explain why calcium-channel antagonists are helpful for a select group of patients with PAH? Why might such drugs be dangerous, or even fatal, if used without first demonstrating acute vasoreactivity? Use the accompanying editorial.
  • Use the multiple-choice questions at the end of In the Clinic: Pulmonary Hypertension to help organize a teaching session, and log on to enter your answers for CME credit.

Humanism and Professionalism


On Being a Doctor: Kaleidoscope

In his essay, Dr. Ely tells how he reminds himself to look through a kaleidoscope to discover unexpected wonders in his patients.

Use this essay to:

  • Listen to an audio recording, read by Dr. Michael LaCombe.
  • Ask your readers what wonder they recently discovered with one of their patients that made caring for him or her more fun and rewarding. Ask if they actively seek out such treasures.
  • Read the quote Dr. Ely offers from his mentor: “Medicine has as its means diagnosing, curing, and saving lives toward the end goal of preserving and improving health, self-worth, and personal dignity. Do not confuse the ‘means' with the ‘end.’ To accomplish the means at the expense of the end is to fail.”
  • Ask your learners what this means.

Video Learning

Medical Knowledge
Patient Care
Consult Guys logo

The Consult Guys: Too Close for Comfort?

In this installment of the consultative medicine talk show, the Consult Guys ask how long anticoagulation need be held for an epidural procedure. Relax with your learners for a few minutes while you watch the video and learn. Answer the short multiple-choice questions to earn CME.

Other Resources From the ACP


Fellowship in High Value Care for Trainees

Help your residents build their CVs while meeting your program’s research and quality improvement requirements. The American College of Physicians is excited to announce the Choosing Wisely High Value Care (CW HVC) Fellowship, funded by the ABIM Foundation, the American College of Physicians, and the Section on Evidence-based healthcare of the NY Academy of Medicine. The CW HVC fellowship offers first- and second-year residents or fellows the opportunity to work to reduce inappropriate health care and learn about the science of knowledge translation. Participants will attend the 3-day NY Academy of Medicine TEACH Program in NYC from August 5-7, 2015, where they will study knowledge translation and plan a local implementation project to reduce unnecessary care, and will then receive support to complete and disseminate their project. Evidence-based medicine and knowledge translation mentors and ACP statisticians will help support the work and its dissemination, including presentation at the ACP Internal Medicine Meeting 2016 and publication in a peer-reviewed journal. For more information or to apply for the fellowship please go to


A 27-year-old woman is evaluated for a 2-day history of fever, hemoptysis, and chest pain. She was recently diagnosed with acute myeloid leukemia and completed her last course of chemotherapy 2 weeks ago. Her course has been complicated by profound neutropenia, thrombocytopenia, and fever that initially resolved after treatment with cefepime and vancomycin.

On physical examination, temperature is 38.9 °C (102.0 °F), blood pressure is 110/70 mm Hg, pulse rate is 100/min, and respiration rate is 20/min. A friction rub is heard at the left posterior lung base.

Laboratory studies indicate a leukocyte count of 100/μL (0.10 × 109/L). Serum galactomannan antigen immunoassay results are positive, consistent with a diagnosis of invasive pulmonary aspergillosis.

A chest radiograph shows a pleural-based nodular density at the left lung base.

A CT scan of the chest is shown:


Which of the following is the most appropriate treatment?

B.Liposomal amphotericin B

Correct Answer
D. Voriconazole

Key Point
Voriconazole is the drug of choice for immunocompromised patients with invasive pulmonary aspergillosis.

Educational Objective
Treat invasive pulmonary aspergillosis in a patient with leukemia.

This patient should be treated with voriconazole. She has probable invasive pulmonary aspergillosis, for which acute leukemia with profound and prolonged neutropenia is a risk factor. She has classic symptoms and signs of an angioinvasive fungal infection, including fever, cough, chest pain, hemoptysis, and pulmonary nodules on chest radiograph. In addition, her CT scan demonstrates evidence of the “halo sign,” which is an area of low attenuation surrounding a nodule, reflecting hemorrhage into the tissue surrounding the fungus. The halo sign is not diagnostic of aspergillosis and may occur in infection caused by other angioinvasive fungi. Evidence from a large randomized controlled trial supports voriconazole as the treatment of choice in patients with invasive aspergillosis. Standard procedures for establishing a definitive diagnosis of pulmonary aspergillosis are bronchoalveolar lavage with or without biopsy, transthoracic percutaneous needle aspiration, or video-assisted thoracoscopic biopsy. The galactomannan antigen immunoassay is an important non–culture-based method of diagnosing invasive aspergillosis. It has good sensitivity in detecting invasive aspergillosis in patients with hematologic malignancy. When combined with early use of CT, the serum galactomannan antigen immunoassay permits early treatment with antifungal therapy.

Liposomal amphotericin B may be considered an alternative primary therapy for some patients. Amphotericin B formulations, itraconazole, posaconazole, and echinocandin agents such as caspofungin and micafungin are appropriate as salvage therapy in patients who are refractory to, or intolerant of, voriconazole.

Walsh TJ, Anaissie EJ, Denning DW, et al; Infectious Diseases Society of America. Treatment of aspergillosis: clinical guidelines of the Infectious Diseases Society of America. Clin Infect Dis. 2008;46(3):327-360. PMID: 18177225

This question is derived from MKSAP® 16, the Medical Knowledge Self-Assessment Program.

From the Editors of Annals of Internal Medicine and Education Guest Editor, Gretchen Diemer, MD, FACP, Program Director in Internal Medicine, Thomas Jefferson University.


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