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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