when good pleural effusions go bad cheryl pirozzi, m.d. pulmonary grand rounds december 16, 2010

When Good Pleural Effusions Go Bad

Cheryl Pirozzi, M.D.

Pulmonary Grand Rounds

December 16, 2010

What is the common pathology?

www.bikerumor.com

The Case

• CC: Pulmonary consult for right pleural effusion

HPI

• 71 yo man admitted 2 days previously with 1d h/o RUQ pain and right-sided chest pain.

• Pain is increased with deep breaths• Increased SOB from baseline• Dry nonproductive cough• No f/c, orthopnea, no change LE edema • No change with eating. No N/V, diarrhea,

BRBPR

PMH

ILD• Initially developed dry cough and SOB in Jan 2010. • HRCT 2/25/10 showed ILD most c/w NSIP• Long hospitalization 4/21/10 - 6/2/10:

– CAP– AF with RVR– Respiratory failure requiring mechanical ventilation – Progression of ILD

• VATS wedge biopsy of RUL and RML 5/7/10 most consistent with mixed cellular/fibrotic NSIP

– Treated with steroids good clinical response– Currently tapered to prednisone 20mg po BID

PMH

ILD – HRCT 2/25/10

PMH

ILD – HRCT 2/25/10

PMH

ILD – HRCT 2/25/10

PMH

ILD- CTA 4/16/10

PMH

ILD- CTA 4/28/10

PMH

• DM2• HTN• Atrial Fibrillation• Gout• Right upper-extremity DVT• 2003 total hip replacement due to OA• Admission 8/10 with hyperglycemia• Admission 9/10 with non-cardiac CP

SH

• From the Congo, emigrated to UT in 2003• No travel since then• No h/o tobacco, EtOH, drugs• Married with 8 children• Previous work as a security officer. No

significant exposures

FH• Noncontributory

Home Meds• Prednisone 20 mg PO bid• Arformoterol nebs BID• Budesonide nebs BID• Albuterol nebs prn• Dapsone 100 mg PO daily • Warfarin• Sotalol• Omeprazole • Simvastatin • Norvasc• Lantus and novolog insulin• Allopurinol• Glipizide

Current Meds• Prednisone 20 mg PO bid• Budesonide nebs BID• Albuterol nebs prn• Dapsone 100 mg PO daily • Warfarin• Sotalol• Omeprazole • Simvastatin • Norvasc• Lantus and novolog insulin• Allopurinol• Glipizide• Miralax • Morphine

On presentation

• VS t 37.6, p 101, 126/75, R 15, SpO2 > 90%/3L• RUQ TTP on exam

• Labs: • WBC 24 (PMN 92%), BUN 18, Cr 0.9 • Lactate 2.5, LFTs nl, lipase 16, INR 3.6

Hospital Course

• Admitted to Medicine on 10/18/10• Pain- negative work up for GI causes• Attributed to constipation• HD 3 patient developed fevers

• On review of admission imaging, attending noted a loculated right pleural effusion, pulmonary consult called

Physical exam

• VS t 38.6, p90, 130/70, R 16, 96%/4 lpm• Gen: obese, alert, oriented, no respiratory distress• HEENT: Mallampati class III airway, OP clear• CV: RRR, no m/g/r. JVP 3 cm/SA• Lungs: crackles bilat, Egophony at R base,

decreased BS R base and laterally mid axillary line. TTP R chest wall on mid axillary line.

• Abd: TTP RUQ, neg Murphy’s, mildly distended• Ext: 1+ edema

Labs

• WBC 20 (PMN 93%), Hgb 11, hct 34, plt 221• Na 141, k 4.6, Cl 107, CO2 27, bun 11, Cr 0.8,

glc 189• INR 2.4

CXR 10/18/10

CTA 10/18/10

CTA 10/18/10

CTA 10/18/10

Impresssion

• Right loculated pleural effusion in immunosuppressed pt with underlying ILD

• Concerning for empyema

• Diagnostic thoracentesis recommended

Hospital Course

• Started on Zosyn, vancomycin, and azithromycin• FFP given to reverse INR• Bedside ultrasound guided thoracentesis

attempted no tap done• Pt sent to radiology for ultrasound-guided

thoracentesis– Unable to obtain any fluid

– Small amount in needle was sent for culture

• Patient refused any more procedures• Plans made for discharge with home IV Zosyn.

Hospital Course

• Just prior to discharge…• Culture from thoracentesis needle AND blood

cultures grew this organism:

Hospital Course

What is the pathogen?• A) Mycobacterium tuberculosis• B) Actinomyces israelii• C) Streptococcus pneumoniae • D) Nocardia cyriacigeorgica• E) Aspergillus fumigatus

Hospital Course

What is the pathogen?• A) Mycobacterium tuberculosis• B) Actinomyces israelii• C) Streptococcus pneumoniae • D) Nocardia cyriacigeorgica• E) Aspergillus fumigatus

Pulmonary Nocardiosis• Nocardia spp = genus of aerobic actinomycetes • Gram-positive bacilli, branching, beaded,

filamentous, weakly acid-fast• Ubiquitous, soil-dwelling organisms

Curr Opin Pulm Med. 2006 May;12(3):228-34

Sputum gram stainwww.theaidsreader.com

Bronchial wash partial acid fast stainthunderhouse4-yuri.blogspot.com

Pulmonary Nocardiosis

• Mainly opportunistic infection, but can also affect immunocompetent hosts (~ 1/3)

• Uncommon; 500 – 1000 cases per year in USA– Incidence thought to be increasing due to more

immunosuppressed pts

Curr Opin Pulm Med. 2006 May;12(3):228-34 Respirology. 2007;12(3):394-400Respir Med 2003; 97:709-717

Pulmonary Nocardiosis

• Most common cause of nocardiosis in humans = N. asteroides complex (> 80% in pulm dz). – N. cyriacigeorgica is an “emerging infection” recently

identified new species, part of N. asteroides complex– 1st described case of pulmonary dz in USA: PNA in a

heart transplant recipient.– Schlaberg et al. Nocardia cyriacigeorgica, an emerging pathogen in the

United States. J Clin Microbiol. 2008 Jan;46(1):265-73. Epub 2007 Nov 14

Curr Opin Pulm Med. 2006 May;12(3):228-34

Nocardiosis

• Most common site of infection is the lung (>2/3 of cases)• Most infections result from inhalation of bacilli• No person to person spread

• ~ 50 % of all pulmonary cases disseminate to sites outside the lungs, most commonly the brain

• Can also involve skin, soft tissue, and almost every organ system

• Nocardemia seen most often with pulm disease, but + blood cultures are rare

Curr Opin Pulm Med. 2006 May;12(3):228-34Medicine 2004; 83:300-313Murray and Nadel 5th ed

Risk Factors

• Which of the following have been identified as risk factors for pulmonary nocardiosis?

• A) COPD• B) alveolar proteinosis • C) Steroids• D) Female gender• E) organ transplant recipients• F) pulmonary fibrosis

Risk Factors

• Which of the following have been identified as risk factors for pulmonary nocardiosis?

• A) COPD• B) alveolar proteinosis • C) Steroids• D) Female gender• E) organ transplant recipients• F) pulmonary fibrosis

Risk Factors

• Impairment of lung defenses: COPD, pulmonary fibrosis, silicosis, alveolar proteinosis

• Systemic immunosuppression due to drug therapy, infection, or malignancy– Corticosteroids (74% of cases)– Cytotoxic therapy– Organ transplant recipients– AIDS with CD4 count <100– Leukemias and lyphomas

• Male gender• Alcoholism a RF for CNS dissemination

Respirology. 2007;12(3):394-400, Medicine 2004; 83:300-313; Curr Opin Pulm Med. 2006 May;12(3):228-34

Risk Factors• Martinez et al. Pulmonary nocardiosis: risk factors and outcomes.

Respirology. 2007;12(3):394-400.• Observational study of 31 pts with pulm nocardiosis (11 with disseminated

nocardiosis)

• Insert table of rfs

• 94% had identifiable RFs• Most common RFs were corticosteroids (65%) and other

immunosuppressive therapy (36%)

Pulmonary Nocardiosis

Clinical presentation- diverse• May be acute, subacute, or chronic • Sxs: fever, chills, night sweats, productive

cough, weight loss, anorexia, dyspnea and hemoptysis, pleuritic chest pain

• Can present with acute, fulminant PNA• Can be complicated by chest wall invasion,

empyema necessitans, mediastinitis, pericarditis, SVC syndrome

Curr Opin Pulm Med. 2006 May;12(3):228-34Murray and Nadel 5th ed

Pulmonary Nocardiosis

Clinical presentation• s/sx of other organ involvement:

– Neurologic signs of mass lesion– Subcutaneous abscesses with or without sinus tracts

Murray and Nadel 5th edMedicine 2004; 83:300-313

Pulmonary Nocardiosis

Radiographic findings- wide variety:• single or multiple nodules • lung masses (with or without cavitation)• reticulonodular infiltrates • lobar consolidation • subpleural plaques • pleural effusions (10-33%) • Upper lobe disease is common

Curr Opin Pulm Med. 2006 May;12(3):228-34Medicine 2004; 83:300-313

Pulmonary NocardiosisRadiographic findings• Pulmonary nocardiosis re-visited. Respir Med 2003; 97:709-717

• retrospective review of clinical and laboratory features of 35 pts with pulmonary nocardiosis

Pulmonary Nocardiosis

• Nodules

Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med. 2006 May;12(3):228-34

Pulmonary Nocardiosis

• Mass-like consolidation

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med 2003; 97:709-717

Pulmonary Nocardiosis

• Consolidation

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med 2003; 97:709-717

Pulmonary Nocardiosis

• Multiple cavitating pulmonary nodules

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med 2003; 97:709-717

Pulmonary Nocardiosis

• Ground glass opacities

Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med 2003; 97:709-717

Pulmonary Nocardiosis

• Pleural effusion

imaging.consult.com jcp.bmj.com

Nocardiosis

• CNS dissemination

jcp.bmj.com

Diagnosis

• Gram stain and a modified acid-fast stain of sputum, pleural fluid, or BAL

Curr Opin Pulm Med. 2006 May;12(3):228-34 Murray and Nadel 5th ed

Modified acid-fast stain of sputum containing Nocardia asteroides shows filamentous branching organismsMurray and Nadel 5th ed

Diagnosis

Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med. 2006 May;12(3):228-34

Diagnosis

• Culture: growth usually within 3 to 7 days but may take up to 3 weeks

• Although the organism occasionally colonizes the upper respiratory tract, recovery of Nocardia from culture of sputum or BAL usually means Nocardia infection

• Often initially misdiagnosed as malignancy or TB

Curr Opin Pulm Med. 2006 May;12(3):228-34Murray and Nadel 5th ed Medicine 2004; 83:300-313

Diagnosis

• Lung biopsy: necrotizing PNA

Respir Med 2003; 97:709-717

Treatment

• Which antibiotic(s) would you use to treat this patient?

• A) Imipenem• B) Zosyn• C) azithromycin• D) Bactrim• E) ceftriaxone• F) clindamycin • G) doxycycline

Treatment

• Which antibiotic(s) would you use to treat this patient?

• A) Imipenem• B) Zosyn• C) azithromycin• D) Bactrim• E) ceftriaxone• F) clindamycin • G) doxycycline

Treatment

• Tends to relapse or progress despite appropriate therapy

• Adequate drainage or excision of abscesses and empyema is crucial

• Duration:– Immunocompetent patients without CNS dz 6–12

months. – Immunosuppressed patients1 year + if possible

dose of immunosuppressant drug– CNS involvement at least 1 year

Murray and Nadel 5th ed Respirology. 2007;12(3):394-400

Treatment

Abx choice• Martinez et al. Pulmonary

nocardiosis: risk factors and outcomes. Respirology. 2007;12(3):394-400.

• Observational study of 31 pts with pulm nocardiosis– 65% N. asteroides

• Most were sensitive to:– amikacin (100%)– TMP-SMZ (95%)– imipenem (93%)– 3rd gen cephalosporins

(90%)

Treatment

Abx choice• Much resistance and treatment failure• No prospective randomized trials• Most recommend empiric treatment with 2 or 3 abx in

severe infection– (pulmonary, CNS, disseminated, and all infections in

immunocompromised pts)

• IV x 3-6 weeks, then can change to PO if improving• 1st line TMP-SMX• Other options: carbapenems, amikacin, 3rd gen

cephalosporins, doxycycline, linezolid, minocycline• Tailor therapy based on susceptibilities Medicine 2004; 83:300-313Curr Opin Pulm Med. 2006 May;12(3):228-34UpToDate.com

Prognosis

• Mortality – Pulmonary dz: 15 – 30%– Higher mortality for acute presentations (~ 66%)– CNS disease 40% to 87%– Nocardemia 44%–85%

• Treatment failure in disseminated disease up to 20%

Murray and Nadel 5th ed Medicine 2004; 83:300-313 Respirology. 2007;12(3):394-400

Our patient

• Initially refused surgery. Treatment started with Bactrim IV, imipenem IV, and doxycycline IV.

• Eventually pt agreed to surgery, and underwent right thoracotomy, decortication, and evacuation of empyema on 10/28/10.

• OR noted empyema “gross purulence” and fibrothorax

• OR Tissue gram stain + nocardia• MRI brain negative for nocardia abscesses• Uncomplicated surgery, recovered well.

Our patient

• Based on sensitivities imipenem changed to ceftriaxone

• At time of discharge doing well, on 1-2 LPM O2• Discharged to SNF on bactrim DS 2 tab PO tid x

at least 12 months, ceftriaxone 1g IV q12 x at least 6 weeks, and doxycycline 100mg PO BID

• Prednisone decreased to 20 mg po daily• ID and pulm follow up

What is the common pathology?

A: NOCARDIOSIS

References• Martinez Tomas R, Menendez Villanueva R, Reyes Calzada S, et al.

Pulmonary nocardiosis: risk factors and outcomes. Respirology. 2007;12(3):394-400.

• Hui CH, Au VW, Rowland K, et al. Pulmonary nocardiosis re-visited: experience of 35 patients at diagnosis. Respir Med 2003; 97:709-717

• Menendez R, Cordero PJ, Santos M, et al. Pulmonary infection with Nocardia species: a report of 10 cases and review. Eur Respir J 1997; 10:1542-1546

• Uttamchandani RB, Daikos GL, Reyes RR, et al. Nocardiosis in 30 patients with advanced human immunodeficiency virus infection: clinical features and outcome. Clin Infect Dis. 1994;18(3):348-53.

• Lederman ER, Crum NF. A case series and focused review of nocardiosis: clinical and microbiologic aspects. Medicine 2004; 83:300-313

• Yildiz O, Doganay M. Actinomycoses and Nocardia pulmonary infections. Curr Opin Pulm Med. 2006 May;12(3):228-34.

• Schlaberg R, Huard RC, Della-Latta P. Nocardia cyriacigeorgica, an emerging pathogen in the United States. J Clin Microbiol. 2008 Jan;46(1):265-73. Epub 2007 Nov 14.

• Nocardiosis. Murray and Nadel 5th ed• Chapman S. Treatment of Nocardiosis. UpToDate.com 2010