Tuesday Case Conference

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Tuesday Case Conference
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History

• 67 yr old man, former smoker, with h/o stage I
  poorly differentiated NSCLC s/p RML resection in
  1996.
• He is followed with annual surveillance chest
  CTs which have all been negative. However, in
  May 2002 he has an abnormal CT.
• Denies cough, CP, SOB, F, C, NS or wt loss

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• PMHx
• CAD s/p PTCA with stent
• Pneumonia in 2/2002
• Hyperlipidemia
• HTN
• Medications
• ASA
• Prinivil
• Pravachol
• Metoprolol

SH 30 pk yrs, quit 20 yrs ago No EtOH, no
IVDU No asbestos Married, monogomous Retired
banker Lives in SF FH n/c
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• Labs
• 13.7 52 PMNs
• 4.3 293
• 41.4
• 139 102 14
• 4.3 25 0.9
• LFTs normal
• Coags normal

• Exam
• T98.7 BP167/78 P65 RR16 100 on RA 71
  kg
• Gen NAD AOx3
• HEENT WNL
• No palpable LN
• CV RRR no M/G/R
• Lungs CTA bilat
• Abd SNTND, nl BS
• Ext No CCE
• Neuro WNL

91
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3/2001
5/2002
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3/2001
5/2002
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• CT report
• Precarinal lymph node, enlarged since prior
  study, measuring 1.9 x 2.4 cm.

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• CT report
• Precarinal lymph node, enlarged since prior
  study, measuring 1.9 x 2.4 cm.
• Differential Diagnosis?
• Next step?

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6/2002
5/2002
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• CT report
• Slight interval increase in size of precarinal
  lymph node, now measuring 2.2 x 2.7 cm. No new
  mediastinal or hilar adenopathy is identified.

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• CT report
• Slight interval increase in size of precarinal
  lymph node, now measuring 2.2 x 2.7 cm. No new
  mediastinal or hilar adenopathy is identified.
• PET
• Fairly intense uptake is identified within the
  known precarinal lymph node, otherwise negative.

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Patient is referred to chest clinic. Bronchoscopy
with needle aspiration of precarinal lymph node,
sent for cytology, routine culture and stain,
fungal and AFB.
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Patient is referred to chest clinic. Bronchoscopy
with needle aspiration of precarinal lymph node,
sent for cytology, routine culture and stain,
fungal and AFB. Cytology was negative. Gram
stain, fungal stain and AFB smear all negative.
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Patient is referred to chest clinic. Bronchoscopy
with needle aspiration of precarinal lymph node,
sent for cytology, routine culture and stain,
fungal and AFB. Cytology was negative. Gram
stain, fungal stain and AFB smear all
negative. Next step?
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12 days later AFB culture is positive for weakly
acid-fast staining organisms (by Kinyoun).
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12 days later AFB culture is positive for weakly
acid-fast staining organisms (by Kinyoun).
Culture positive for Nocardia asteroides.
Patient is started on Septra, with plan to treat
for several weeks then repeat chest CT.
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Pulmonary Nocardiosis
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Nocardia Microbiology
Nocardia species are aerobic gram positive rods
that appear as beaded, branching filaments. They
are morphologically similar in appearance to
actinomyces. Weakly acid-fast by Kinyoun, (not
by Auramine). Murray-Nadel, Textbook of
Respiratory Medicine, 3rd ed.
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Actinomycetes

• Anaerobic Aerobic
• Actinomyces Nocardia
• Arachnia Gordona
• Rothia Streptomyces
• Bifidobacterium Mycobacterium
• Rhodococcus
• Corynebacterium
• Actinomadura
• Dermatophilus

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Nocardia Species

• N. asteroides (80 of human infection)
• N. brasiliensis
• N. farcinia
• N. nova
• N. otitidiscaviarum
• N. transvalensis

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Nocardia Epidemiology

• Nocardia is a ubiquitous soil bacteria.
  Nocardiosis is rare. It is estimated that there
  are 500 to 1000 new cases per year in the U.S.
• There are several predisposing conditions,
  although 36 of cases had no predisposing in one
  series.

• Predisposing Factors
• Malignancy
• AIDS
• Steroids
• Diabetes
• Alcohol
• Alveolar Proteinosis
• Granulomatous disease
• COPD
• Bronchiectasis

Beaman et al., J Inf Dis 1976, 134286 Georghiou
et al., Med J Aust 1992, 156 692
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Extrapulmonary Nocardiosis
Nocardia enters through the lung or skin and can
disseminate or go to multiple sites. Regional
lymph node involvement noted in cutaneous
nocardiosis. Nocardia seems to have a certain
predilection for the CNS (20 of the time).
Mandell, Principles and Practice of Infectious
Disease, 5th ed Georghiou et al, Med J Aust,
1992, 156592
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Pulmonary Nocardia Clinical Presentation

• Symptoms are can be progress over several weeks.
• Low grade fever
• Weight loss
• Productive cough
• Hemoptysis
• Fatigue
• Pleuritic chest pain

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Radiographic appearance is variable

• Single or multiple nodules/masses
• Cavitary lesions
• Reticulonodular
• Interstitial infiltrates
• Lobar consolodation
• Subpleural plaques
• Pulmonary Effusions
• Lerner et al., Clin Inf Ds 1996, 22891

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Nocardia Diagnosis

• Several factors can make the diagnosis difficult
• Slow growth (up to 2 to 3 weeks)
• Over growth of other contaminating organisms
• Lack of specific clinical or radiographic
  characteristics
• In one series 44 of patients with pulmonary
  nocardia required an invasive procedure to make
  the diagnosis (bronchoscopy, thoracentesis,
  thoracotomy, autopsy).
• Sensitivity of invasive sample estimated at 90.
  Clinically insignificant colonization of nocardia
  has been reported.

McNeil et al, Clin Micro Rev 1994, 7377-383
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Nocardia Treatment

• Lack of clinical trials makes optimal treatment
  unclear.
• Sulfonamides, especially TMP-SMZ, considered to
  be the drug of choice. Optimal dose unclear, most
  recommend 2.5-10 mg/kg of TMP and 12.5-50 mg/kg
  of SMZ (1 to 4 DS tabs per day).
• Duration of therapy also not known. Most
  recommend 2 to 12 months.

Lerner et al., Clin Inf Ds 1996, 22891
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Nocardia Treatment

• Alternative treatments bases on in vitro activity
  and anecdotal success. Informal poll of IDSA
  members suggests
• Severely ill
• IV amikacin, imipenem or 3rd gen cephalosporins.
  
• Less ill
• Oral minocycline

Beaman et al., J Med Vet Mycol 1992, 30317
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Prognosis

• Prognosis depends on extent of disease and immune
  status of the patient.
• For disseminated nocardiosis the mortality is 7
  to 44 in immunocompetent patients mortality is
  gt85 in immunocompromised patients.

Beaman et al., J Inf Dis 1976, 134286
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Case (continued) The patient was treated with
Septra for several weeks. A repeat CT was
obtained which showed enlargement of the lymph
node. A mediastinoscopy was performed, biopsy
of the lymph node consistent with recurrence of
NSCL cancer, cultures were negative.
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Conclusions

• Nocardia is a rare cause of pulmonary infection
• Would consider in immunocompromised patient with
  subacute or chronic symptoms
• CXR often shows bilateral nodules, but can
  present in different patterns
• Optimal treatment not known, TMP-SMZ most
  commonly used