Morning Report Date: December 2, 2005 Hospital: MCV Hospitals Presenter: Venkat Ramachandran Brief case Description: A 60 year-old-man

presents to the ER with complaints of fevers, chills, skin nodules and a non-resolving right-sided pneumonia. The consolidative process has persisted for 3 months despite 2 courses of oral anti-microbials and 1 course of intravenous anti-microbials. Chest CT revealed dense consolidation in the right middle and lower lobes. His skin nodules were biopsied and silver stain revealed presence of Blastomyces dermatidis. Culture grew B dermatidis. A diagnosis of pulmonary and cutaneous blastomycosis was made and oral itraconazole was started. The patients condition improved and at a 6-week follow up visit, he was asymptomatic.

Teaching points: 1. Non-resolving pneumonia In evaluating and treating patients with slowly resolving pneumonias, it is important to understand the definitions of progressive versus nonresolving pneumonia. Progressive pneumonia is an acute process defined as clinical deterioration after 24 hours of treatment with an increase in 50% in the extent of the pulmonary opacities on chest roentrogram, respiratory failure requiring ventilation of septic shock after 72 hours of treatment. Non-resolving pneumonia is a clinical syndrome in which focal infiltrates begin with some clinical association of acute pulmonary infection (fever, productive cough, dyspnea) and despite at least 10 days of antibiotic therapy patient do not improve or worsen as indicated by clinically or by failure of radiographic opacities to resolve within 12 weeks of the onset of pneumonia. The differential diagnosis of a non-resolving pneumonia requires the evaluation of several factors to include host factors (age, comorbidities, HIV, primary humoral immune deficiency), severity of disease and the clinical pathogen. Host factor comorbidities include presence of COPD, alcoholism, neurologic disease, CHF, CKD, malignancy and DM. The severity of disease is an important factor in the determination of outcome measures. The Pneumonia Severity Index developed by Fine et.al. provides a means of stratifying groups of patients according to mortality risk. The clinical pathogen and its correct identification and treatment is vital in the evaluation of nonresolving pneumonias. The differential diagnosis to consider includes: 1. Bacterial Pathogens A. Nonresolving or slowly resolving pneumonia more common with severity of disease at presentation, multi-lobar disease and infection with drug-resistant organisms B. Strept pneumo: esp. with bacteremia, persistent fever/leukocytosis > 6 days, advanced age, COPD, ETOH C. Legionella: esp. w/ tobacco/ETOH abuse, age >65 yrs, immunosuppressed, CKD, BM Tx 2. Misdiagnosis of Pathogen: Consider Fungi, TB, Nocardia/Actinomyces 3. Resistant Pathogens 4. Complication of the initial pneumonia: Empyema or Lung Abscess (esp. with h/o previous aspiration, poor dental hygiene, alcoholism and h/o seizures) 5. Non-infectious etiologies A. Malignancy (Bronchogenic carcinoma, Broncho-alveolar cell carcinoma, Lymphoma)

B. Inflammatory Disorders: Systemic Vasculitis (Wegners), Eosinophilic Pneumonias, Pulmonary Alveolar Proteinosis, Cryptogenic organizing pneumonitis, AIP, Sarcoidosis C. Drug induced lung disease (Amiodarone, MTX, Bleomycin) D. PTE with infarction E. Hydrostatic/Cardiogenic pulmonary edema F. PTE with infarction
(Low DE. Progressive Progressive and nonresolving pneumonia. Curr Opin Pulm Med. 2005 May;11(3):247-52., Weyers, CM. Nonresolving pneumonia. Clin Chest Med. 2005 Mar;26(1):143-58.)

2. Evaluation of nonresolving pneumonia Normal resolution of pneumonia is variable and depends on the causative agent, severity of disease at presentation and host factors. Approach to the evaluation of a nonresolving pneumonia should begin with an assessment for risk factors that may contribute to delayed resolution. Specifically, the patients age and comordities, the severity of the pneumonia and the specific pathogen if identified. Different pathogens have different rates of resolution. Resolution may be consider clinically (defervescence, resolution of leukocytosis as well as radiographically). If the rate of resolution does not appear appropriate, it is important to revisit the history and assess for indications of unusual pathogens and noninfectious agents (careful assessment of social history, travel, exposures and risk factors for atypical and non-infectious causes). A chest CT and laboratory evaluations (serologies, sputum samples, antigen testing) is the next step in evaluation. If these studies are unrevealing, consider bronchoscopy. Bronchoscopy is most useful in young non-smoking, immunocompetent young patients with prolonged multilobar disease. Bronchoscopy may identify organisms that are not responding to initial antibiotic regimen, but unclear if this improves outcome. The limitations of bronchoscopy include (1) late availability of information (2) simpler methods such as tracheal aspiration culture that can provide information in a simpler, less invasive and more expedient manner (3) repeat testing usually isolates highly resistant organism that would not be eliminated by changes in antibiotic therapy.
(Menendez R. Evaluation of nonresolving and progressive pneumonia. Semin Respir Infect. 2003 Jun;18(2):103-11., Niederman, MS. Bronchoscopy in nonresolving nosocomial pneumonia.Chest. 2000 Apr;117(4 Suppl 2):212S-218S.)

3. Quick Review: Blastomycosis Blastomycosis should be considered in all patients with a history of non-resolving pneumonia who live in an endemic area. Specific questions regarding outdoor exposures to soil and dust are important. The diagnosis of Blastomycosis can be made by direct visualization of the fungus from sputum, tissue or other infected fluid. This can be done by papanicolau staining (93% diagnostic yield). B. dermatidis can be cultured from tissue as well. Available serologic testing (complement fixation, immunodiffusion) are not reliable. Blastomycosis pulmonary infections typically present as a mild self-limiting disease. In mild or progressive pulmonary disease in an immunocmpetent patient without CNS involvement, initial treatment with Itraconazole for 6 months (cure rate > 60%) may be appropriate. Infections complicated by respiratory compromise/ARDS or CNS involvement or infection in an immunocompromised host should be treated with IV Amphotericin.
(Shah B. North American blastomycosis: the importance of a differential diagnosis. Cutis. 1996 Dec;58(6):402-4., Weingardt, J. North American blastomycosis. Am Fam Physician. 1991 Apr;43(4):12458.)