Tag: Nocardia

Microbiology Case Study: A 55 Year Old Man with New Onset Neurologic Deficits

Clinical History

A 55 year old male with a 43-pack-year smoking history was transferred to our hospital for evaluation of new onset neurologic deficits including slurred speech, aphasia, and right upper extremity diminished dexterity and neglect. CT chest was remarkable for a mass in the superior segment of the left lower lobe. Needle core biopsy of the lung mass revealed poorly differentiated non-small cell carcinoma. Head MRI demonstrated an enhancing mass in the left frontoparietal junction that was concerning for metastasis from a lung primary. The patient was started on chemotherapy as an outpatient. Follow-up imaging showed growth of the brain mass. A biopsy of the brain mass showed no evidence of metastasis, only “reactive brain with foci of dense mixed inflammation and filamentous bacteria consistent with abscess.”

Image 1. Head MRI demonstrating left frontoparietal mass.

Laboratory Findings

A portion of the brain biopsy was submitted for bacterial smear and culture. The aerobic culture grew chalky white colonies that, when stained with modified acid-fast stain, showed modified acid-fast positive filamentous bacteria, suspicious for Nocardia spp. Bacteria of similar morphology were also seen in the surgical pathology specimen when stained for modified AFB and with GMS.

Image 2. Blood agar plate growing chalky white colonies.
Image 3. Modified acid-fast positive filamentous bacteria at 1000x.

Disscussion

Nocardia is a genus of aerobic, catalase positive, saprophytic bacteria often found in the environment, but that can also be considered as normal flora on skin and in the respiratory tract. Nocardia species are variably acid-fast; for proper identification they must be stained with a modified acid-fast procedure (Fite, Kinyuon), using a weaker decolorizing acid. Nocardia will be negative by traditional acid-fast staining procedures (Ziehl–Neelsen). When Gram stained, Nocardia will appear as branching filamentous gram-positive bacilli with a “beaded” staining pattern (as if a string of beads). 

Multiple species are considered human pathogens, including N. asteroides, N. brasiliensis, N. cyriacigeorgica, N. farcinica, and N. nova. These organisms can cause disease in immunocompromised patients if inhaled or inoculated via trauma. If there is an established pulmonary infection, Nocardia may spread hematogenously, often infecting the brain. 

Central nervous system nocardiosis may occur in any region in the brain and can present with mass effect symptoms without typical infectious symptoms, as in our patient. Prognosis varies based on the extent of disease and the cause of a patient’s immunosuppression. Treatment of CNS nocardiosis usually begins with an induction phase of intravenous TMP-SMX and imipenem for 3-6 weeks or until there is clinical improvement. Once the patient improves, they can be switched to oral therapy with a sulfonamide and/or minocycline and/or amoxicillin-clavulanate.  

References

  • Beaman BL. Nocardia Species : Host-Parasite Relationships. 1994;7(2):213-264.
  • Spelman D. Clinical manifestations and diagnosis of nocardiosis. In: Sexton DJ, Mitty J, eds. UpToDate. UpToDate, Inc.
  • Spelman D. Microbiology, epidemiology and pathogenesis of nocardiosis. In: Sexton DJ, Mitty J, eds. UpToDate. UpToDate, Inc.
  • Spelman D. Treatment of Nocardiosis. In: Sexton DJ, Mitty J, eds. UpToDate. UpToDate, Inc.
  • Tille, Patricia M., PhD, BS, MT(ASCP) Facs. Bailey & Scott’s Diagnostic Microbiology. 14th ed. Elsevier; 2017.

-Michael Madrid, MD is a 1st year Anatomic and Clinical Pathology Resident at the University of Vermont Medical Center.

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Associate Professor at the University of Vermont.

Microbiology Case Study

Patient History:

81 year old man with a history of systemic vasculitis (present for the past 10 years ANCA negative, ANA negative, Rheumatoid factor <20) on immunosuppression (plaquenil with prednisone 40mg for flares about every 6 months), type 2 diabetes, and hypertension presented to an outside hospital with weakness and dyspnea. He was found to have a widespread purpura, ulcerative lesions, acute kidney injury (creatinine 4.7), and 3 days of hematochezia. He was started on 7 days of levoquin and zosyn for a presumed pneumonia and with no improvement was transferred to our institution. On admission, a CT scan of the chest demonstrated bilateral multifocal pneumonia and multiple cavitary nodules within the lungs. A thoracentesis was performed and was transudative (wbc 1883, N 63%, protein 2.6).

Laboratory findings:

  • WBC 7000/cmm
  • Hemoglobin 9 g/dL
  • Platelet count 104 K/cmm
  • Bacterial culture blood, no growth
  • Cryptococcal antigen negative
  • Pleural fluid bacterial culture and smear negative
  • Pleural fluid AFB culture and smear – no acid fast bacilli, modified acid fast bacilli seen from bottle
  • Pleural fluid fungal culture and smear – no fungi seen, rare modified acid fast bacilli growing
  • Histoplasma urinary antigen positive
  • Histoplasma antibodies negative
  • Blastomyces urinary antigen negative

Gram stain of growth from the AFB bottle showing beaded, branch Gram positive bacilli.
Gram stain of growth from the AFB bottle showing beaded, branch Gram positive bacilli.

Modified acid fast stain of growth from the AFB bottle showing modified acid fast bacilli.
Modified acid fast stain of growth from the AFB bottle showing modified acid fast bacilli.

Isolated growth on BCYE media.
Isolated growth on BCYE media.

Discussion:

Based on Gram stain and modified acid fast stain, modified acid fast bacilli suggestive of Nocardia species was reported. Nocardia are strict aerobic, gram positive, filamentous rods that stain partially acid fast. This is due to the mycolic acids in the cell wall which are shorter than those of mycobacteria. Nocardia species produce many virulence factors including Cord factor (prevents intracellular killing), catalase and superoxide dismutase (which inactivate reactive oxygen species that would otherwise prove toxic to the bacteria).

Nocardia grow well on buffered charcoal yeast extract agar and at 30oC. They produce aerial hyphae and can have a chalky colony appearance. Species level identification is best done with molecular methods. This isolate was identified as Nocardia farcinica at a reference laboratory.

Nocardia species are ubiquitous in the soil. They can cause infections in immunocompromised hosts usually after inhalation or direct inoculation. Infections include bronchopulmonary disease and cutaneous infections. With bronchopulmonary disease, cavitation and spread to the pleura is common, which fits with our patient. Dissemination is also seen with common sites being brain and subcutaneous tissue.

Our patient had a positive Histoplasma urinary antigen, but negative Histoplasma antibodies. The working diagnosis was disseminated Histoplasmosis and he was being treated with amphotericin B. He expired and no postmortem exam was performed. Fungal cultures from the pleural fluid were not growing fungus at the time of this post. Fungal cultures were not obtained from sputum and a BAL was not performed.

-Dan Olsen, MD is a 4th year anatomic and clinical pathology resident at the University of Vermont Medical Center.

Wojewoda-small

-Christi Wojewoda, MD, is the Director of Clinical Microbiology at the University of Vermont Medical Center and an Assistant Professor at the University of Vermont.