Co-Infection with Nocardia and Mycobacterium Avium Complex (MAC) in a Patient with Acquired Immunodeficiency Syndrome

Zahira Babwani DO

Kenneth Wojnowski Jr DO

Sunil Kumar MD

Broward Health Medical Center

Fort Lauderdale, FL USA

Abstract

We present a case in which a patient with acquired immunodeficiency syndrome (AIDS) and nocardiosis was found to have co-infection with Mycobacterium avium complex (MAC). Despite the fact that MAC is a known colonizer of the pulmonary system, ​ it is possible to have co-infection and a high degree of suspicion is necessary to ensure prompt treatment of both organisms. We wish to describe how radiologic findings were instrumental in guiding our differential diagnosis.

Case Report

History of Present Illness​: A 64-year-old man with history of alcohol and tobacco abuse presented with a chronic, productive cough for 5-6 months. Associated symptoms included shortness of breath and 30-pound weight loss. He denied all other symptoms.

Physical Exam​: Pertinent positives revealed temporal wasting, poor dental hygiene, oral thrush and diffuse rhonchi bilaterally. Initial vital signs were within normal limits.

Laboratory and Radiology​: Pertinent laboratory findings revealed leukocytosis with a left shift. Viral respiratory polymerase chain reaction (PCR) testing was negative. Human immunodeficiency virus (HIV) testing was positive with a CD4 count of 46 cells/mm³. QuantiFERON gold testing was negative. Sputum cultures, acid-fast bacilli (AFB) and blood cultures were obtained. Bronchoalveolar lavage (BAL) was performed with no evidence of Pneumocystis jirovecii (PJP). Chest X-ray (CXR) and computed tomography (CT) of the chest (Figure 1) revealed a multifocal right lung abscess with complex pleural fluid, empyema, nodular cavitary lesion in the left lower lobe and hilar lymphadenopathy.

Figure 1. Panel A: initial chest X-ray shows a complex infiltrate and effusion in the right lung. There is a cavitary lesion with air-fluid level vs lung abscess on the right. A nodule or consolidation is present in the left lung base. Panel B: A representative image from the initial CT of the chest showing a multifocal right lung abscess and complex pleural fluid.

Hospital Course: ​After admission, the patient was started on broad spectrum antimicrobials with vancomycin and piperacillin-tazobactam. A thoracentesis was performed due to right sided pleural effusion which yielded 65 cc of thick, purulent, green fluid. Thoracotomy with complete decortication of the right lung was performed with biopsies of the abscesses. Two 32-French chest tubes were placed due to the presence of multiple intraparenchymal lung abscesses, loculations, and empyema. Biopsy and pleural fluid cultures grew gram positive, beaded organisms which were later identified as nocardia, with no evidence of MAC or Mycobacterium tuberculosis (MTB). The patient was started on amikacin, meropenem and trimethoprim-sulfamethoxazole for newly diagnosed pulmonary nocardiosis. MAC prophylaxis was initiated due to his low CD4 count. After initiation of therapy for nocardiosis, three sputum AFB cultures began to stain positive. Since nocardiosis stains weakly positive for AFB, we initially did not suspect non-tuberculous Mycobacteria (NTM). Repeat CT scan of the chest (Figure 2) revealed ground glass opacities, nodular densities and both mediastinal and hilar lymphadenopathy.

Figure 2. Panel A: after initiation of treatment for nocardiosis, improvement of right empyema and cavitary lesion with bilateral patchy airspace disease right greater than left. Panel B: CT of the chest after initiation of treatment for nocardiosis, prominent lymph nodes in the hilar regions and mediastinum. less cavitation than the previous study. There are innumerable ground glass and nodular densities throughout both lungs, right greater than left.

Suspicion for active MAC co-infection was raised, the prophylactic dose of azithromycin was increased to the treatment dose, and ethambutol was initiated. After three weeks of intravenous amikacin, meropenem and trimethoprim-sulfamethoxazole the patient showed considerable improvement in his respiratory symptoms and was transitioned to oral trimethoprim-sulfamethoxazole for outpatient treatment of nocardiosis with continuation of ethambutol and clarithromycin for MAC.

Discussion

The Mycobacterium Avium Complex ​(MAC) is a Non-tuberculous mycobacterium (NTM) that is commonly found in patients with HIV and a CD4 count of less than 50. The diagnosis of NTM is challenging due to the fact that the organism is a known colonizer of the pulmonary system (1) ​. Supportive radiologic evidence is needed to distinguish colonization from active infection (2).

Common CT findings of nocardiosis include ground glass opacities, lung nodules, cavitation, pleural effusion and masses (3)​. The presence of mediastinal and hilar lymphadenopathy is the most common finding in immunosuppressed patients with MAC infection but is not​ a usual feature of pulmonary nocardiosis (3,4) ​. Our​ patient’s repeat CT scan showed mediastinal and hilar lymphadenopathy with improvement of cavitary lesions which suggests improvement of CT findings related to nocardiosis, but persistent findings related to NTM (5). This led us to believe that the patient was appropriately treated for nocardiosis, but with an underlying presence of active MAC infection that presented with atypical radiographic findings. As per the American Thoracic Society (ATS) guidelines for NTM pulmonary infection (6)​ ​, this patient’s pulmonary symptoms, radiological evidence on the chest CT, and positive AFB cultures from at least two separate expectorated sputum samples lends credibility to MAC as a true active infection in the setting of nocardiosis and AIDS. The patient was appropriately placed on clarithromycin and ethambutol as an outpatient, and our suspicions were confirmed for MAC with no evidence of MTB by PCR testing 5 weeks after initial AFB smears were collected.

Co-infection with Nocardiosis and MAC may be underestimated since they both often develop in immunocompromised hosts. MAC, along with other NTM species account for 20% of mycobacterium pulmonary infections in HIV infected patients (5)​. Nocardia accounts for less than 3% of pulmonary infections in HIV infected patients (5)​. A high degree of clinical suspicion is imperative to promptly treat infection with both organisms.

References

1. Young J, Balagopal A, Reddy NS, Schlesinger LS. Differentiating colonization from infection can be difficult Nontuberculous mycobacterial infections: Diagnosis and treatment. Patient Care. 2007. Available at: http://www.patientcareonline.com/infection/differentiating-colonization-infection-can-be-difficult-nontuberculous-mycobacterial-infections (accessed 10/3/18).
2. Trinidad JM, Teira R, Zubero S, Santamaría JM.Coinfection by Nocardia asteroides and Mycobacterium avium- intracellulare in a patient with AIDS. Enferm Infecc Microbiol Clin. 1992 Dec;10(10):630-1. [PubMed]
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5. Benito N, Moreno A, Miro JM, Torres A. Pulmonary infections in HIV-infected patients: an update in the 21st century. Eur Respir J. 2012 Mar;39(3):730-45. [CrossRef] [PubMed]
6. Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416. [CrossRef] [PubMed]

Cite as: Babwani Z, Wojnowski K Jr, Kumar S. Co-Infection with Nocardia and Mycobacterium avium complex (MAC) in a patient with acquired immunodeficiency syndrome. Southwest J Pulm Crit Care. 2019;18(1):22-5. doi: https://doi.org/10.13175/swjpcc123-18 PDF

Pulmonary Nocardiosis and Empyema in a Patient with Metastatic Neuroendocrine Tumor

Nimesh K. Patel, DO

Linda Snyder, MD

University of Arizona, Department of Medicine. Tucson, Arizona

Reference as: Patel NK, Snyder L. Pulmonary nocardiosis and empyema in a patient with metastatic neuroendocrine tumor. Southwest J Pulm Crit Care 2011;3:28-33. (Click here for a PDF version)

Abstract

Nocardia is a ubiquitous aerobic gram-positive bacterium that can cause local or disseminated infection. Nocardiosis involves the lung in the majority of cases. Nocardiosis is often an opportunistic infection, but can also affect non-immunocompromised hosts. This case report highlights the presence of empyema due to Nocardia cyriacigeorgica infection, an unusual feature of Nocardia pulmonary involvement. 

Case Presentation

History of Present Illness: A 65 year-old male with a history of metastatic neuroendocrine tumor of the pancreas, was admitted to the hospital with a one-week history of hemoptysis, cough, and dyspnea. He was treated for presumed community acquired pneumonia with moxifloxacin two weeks prior to admission. He was receiving monthly octreotide injections for treatment of the neuroendocrine tumor. The patient had no history of corticosteroid use.  

Physical examination:

Vital signs: Temperature 99.9F, Respirations18, Blood Pressure 104/69, Pulse 96, SaO2 91% on oxygen at 2 liters per minute by nasal cannula

General: The patient was in no acute distress. He was alert and oriented to person, place and time.

HEENT: No significant abnormalities.

Chest: Dullness to percussion, mid-lower right thoracic cavity, with scattered crackles. 

Cardiovascular: regular rate, normal S1 and S2, no murmurs appreciated.  Abdomen: positive bowel sounds, soft, non-tender, non-distended, positive hepatosplenomegaly. 

Extremities: +2 pitting edema bilaterally extending to mid-thigh level

Laboratory and radiographic findings: The peripheral white blood cell count was 8, 000 cell/mm³ with a differential as follows 91% neutrophils/bands, 7% lymphocytes, 1% myelocyte, 1% reactive lymphocyte, hemoglobin was 11 g/dL and the platelet count was normal. The basic metabolic panel revealed blood urea nitrogen of 30 mg/dl and creatinine of 1.5 mg/dl. The hepatic panel was normal except for an elevated alkaline phosphatase of 530 IU/L. Coccidioides IgM and IgG serology performed by immunodiffusion were negative.

The chest radiographs from two weeks prior to admission (Figure 1), admission (Figure 2) and admission computerized tomography of the chest (Figure 3) are shown.  

Figure 1. Chest radiograph two weeks before admission:  Right middle lobe consolidation with volume loss and small right pleural effusion

 

Figure 2.  Chest radiograph on admission: Increasing patchy opacifications involving the right upper lobe, right middle lobe, and left lower lobe, with cavity formation noted in the left lung. There is right paratracheal lymphadenopathy noted.

Figure 3: Computerized tomography of the chest showing multifocal consolidation with a necrotizing process containing central lucencies. A loculated, moderate sized right anterior pleural effusion with lucencies is compatible with an empyema.

Hospital course:

Our patient was started on broad-spectrum antimicrobial therapy and underwent chest tube drainage of the loculated effusion.  A sputum gram stain revealed 4+ weakly acid-fast branching bacilli, consistent with Nocardia. The gram stain of the pleural fluid showed 3+ polymorphonuclear cells and 3+ gram-positive, branching, weakly acid-fast bacilli, consistent with Nocardia.  The culture from sputum and pleural fluid grew Nocardia cyriacigeorgica. 

Computerized tomography of the brain showed no intracranial abnormalities. The patient was treated with high dose trimethoprim/sulfamethoxazole, two double strength tablets three times a day with monitoring of sulfamethoxazole levels. The patient clinically improved with antimicrobial treatment and drainage of the empyema. The chest tube was successfully removed and the patient’s symptoms of cough and dyspnea resolved. A chest x-ray showed resolution of the right middle lobe and left lower lobe infiltrative process.

Figure 4.  Chest radiograph post-antimicrobial treatment: Interval resolution of right middle lobe and left lower lobe infiltrative process. Post infectious inflammatory changes are noted in the right middle lobe.

Discussion

Nocardiosis is an important opportunistic infection caused by aerobic actinomycetes in the genus Nocardia. Nocardia asteroides has been considered the most common species to cause human disease, however classification has become more complex with the use of molecular techniques. Species formerly included in the Nocardia asteroides complex are now considered distinct species.  Nocardia cyriacigeorgica is one of the more common isolates and has been noted to cause pleural disease and empyema.  Nocardia species are found in soil and can become airborne; the most common route of entry for infection is inhalation. Effective cell-mediated immunity of the host is crucial to combating infection with Nocardia species.  Two recent reviews of nocardiosis highlight important clinical features of this disease (1,2). The most common symptoms are fever, cough, pleuritic chest pain and headache. Specific risk factors for Nocardia infection are present in the majority of patients and include corticosteroid treatment and immunosuppression. Additional risk factors include malignancy and chronic lung disease. Of interest to pulmonologists, chronic obstructive pulmonary disease (COPD) was a common underlying condition, representing over 20% of patients with nocardiosis in these reports. Common chest radiographic presentations of pulmonary nocardiosis include consolidation, nodules and cavities. The diagnosis of pulmonary nocardiosis is made from sputum and bronchoalveolar lavage specimens in the majority of patients. In addition, recent reviews document that pleural effusions are present in up to 35% of patients with pulmonary nocardiosis.  In one report, when pleural fluid was sampled, Nocardia was isolated in the majority of patients. Nocardia cyriacigeorgica can cause invasive pulmonary disease and was found to be the predominant species in pulmonary nocardiosis in one review.

Summary

Nocardiosis is an important opportunistic pulmonary disease. The diagnosis should be included in the differential diagnosis of pulmonary infiltrates in immunosuppressed populations, including patients after organ transplantation, with advanced HIV infection and those receiving chronic corticosteroid therapy or chemotherapy. Radiographic findings of lung involvement are variable and include single or multiple nodules or cavities, alveolar or interstitial infiltrates, and pleural effusions. This case report highlights the unusual presentation of Nocardia cyriacigeorgica pulmonary infection with extensive cavitary parenchymal disease and concomitant empyema. 

References

1. Minero MV, et al. Nocardiosis at the Turn of the Century.  Medicine 2009;88:250-61.
2. Tomas RM, et al. Pulmonary Nocardiosis: Risk factors and outcomes. Respirology 2007;12:394-400 .
3. Latef SM, et al. Nocardia cyriacigeorgica empyema in 45-yr-old male with dual granulomatous lung disease. Chest 2008 134:c12001.
4. Schlaberg R. Nocardia cyriacigeorgica: an emerging pathogen in the United States.  Journal of Clinical Microbiology 2008;46:265-73.
5. Maraki S. Nocardia cyriacigeorgica pleural empyema in an immunocompromised patient.  Diagnostic Microbiology and Infectious Disease 2006;56:333-5.