Nocardia cyriacigeorgica in an immunocompetent patient

Introduction

Nocardiae are aerobic actinomycetes ubiquitously found in soil and aquatic habitats. They are generally slow growing, beaded, branching Gram-positive rods that are partially acid-fast [Brown-Elliott et al. 2006]. Infections due to Nocardia cyriacigeorgica are invariably reported in immunocompromised patients [Saubolle and Sussland, 2003].The accurate and timely identification of Nocardia species is imperative because this provides a critical guide in the choice of targeted antimicrobial therapy, which, if delayed, may result in grave consequences [Saubolle and Sussland, 2003; Akcaglar et al. 2008]. However, isolation and identification of Nocardia species can be challenging [Menendez et al. 1997]. Here we report an unusual case of N. cyriacigeorgica that occurred in an immunocompetent patient with bronchiectasis in whom the infective process persisted despite repeated courses of antimicrobial therapies.

Case

A 60-year old nonsmoking lady presented with increasing dyspnoea on the background of 3 months’ history of cough productive of purulent sputum. She was known to have history of atopy, alpha-1 antitrypsin MZ carrier and bronchiectasis. She received long-term azithromycin and nebulized promixin due to colonization with Pseudomonas aeruginosa and inhaled corticosteroids (fluticasone 1 mg daily). Prior to hospitalization she had received three courses of antibiotics including amoxicillin, ciprofloxacin and oxytetracycline as well as a short course of oral corticosteroids (OCS) with lack of response. On examination she was afebrile with oxygen saturations of 97% on room air. Respiratory examination confirmed bibasal crepitations. Spirometry showed an FEV1 of 1.4L (64% predicted) and a FVC of 2.6L (98% predicted), which was 1.5L (67% predicted) and 2.4L (90% predicted) 9 months prior, respectively. Her blood white cell count, C-reactive protein (CRP) and biochemical profile were within the normal range. The chest radiograph (CXR) showed bilateral basal pleural thickening (Figure 1a); high resolution computed tomography (HRCT) confirmed extensive emphysema, most marked in the lower lobes with evidence of small airways disease and bronchiectasis as well as multiple indistinct pulmonary opacities affecting all the lobes and multiple small mediastinal nodes (Figure 1b,c). Sputum analysis revealed P. aeruginosa but was negative to mycobacterial culture. Additionally, there were Gram-positive bacilli which by partial sequencing of 16s rDNA polymerase chain reaction (PCR) identified N. cyriacigeorgica. The patient received 7 days’ treatment with intravenous piperacillin/tazobactam followed by 6 weeks of co-trimoxizole. The sputum 3 weeks later showed mixed oral flora and has remained free of Nocardia at 3 and 6 month reviews with improvement in symptoms and lung function .

Figure 1.

(a) Chest radiograph of the patient on admission. This shows essentially no obvious infection-related abnormality, but bibasal pleural thickening. (b, c) Computed tomographic scan slices at two levels of the patient during admission. This shows bronchiectasis and the arrows depict nodular changes suggesting the atypical infection of Nocardia cyriacigeorgica.

Discussion

Here we describe a rare case of pulmonary infection due to N. cyriacigeorgica in an immunocompetent person. The only possible patient predisposing factors in developing this were bronchiectasis, chronic colonization with P. aeruginosa and treatment with inhaled corticosteroids. In our case the suspicion of an atypical infection was raised due to the presence of new radiological abnormalities. A review from Thailand describing 70 cases of nocardiosis reported abnormal chest radiograph in two-thirds of the cases with alveolar and reticulonodular infiltration commonly noted [Mootsikapun et al. 2005]. In our case the radiological abnormalities included widespread pulmonary opacities and mediastinal lymphadenopathy. The pleuropulmonary, skin and soft tissues were the most common clinical syndromes present in 44.3% and 22.8% of cases, respectively. The most frequent respiratory symptoms were of fever and cough. Our patient presented with cough productive of mucopurulent sputum but no history of pyrexia.

N. cyriacigeorgica is a re-designated species originally recognized as the Nocardia asteroides antibiotic susceptibility type VI isolate [Forrester and Forrester, 2011]. Unless there is a high index of clinical suspicion, the diagnosis of pulmonary nocardiosis may be challenging. In a review of 85 reported cases of N. cyriacigeorgica, 27 of the infections were isolated in the lung, three in the brain and one in the eye; in the remaining, the infection sites were unidentified [Brown-Elliott et al. 2006]. Infections with N. cyriacigeorgica were noted in immunocompromised patients due to conditions such as human immunodeficiency virus, poorly controlled diabetes mellitus, rheumatoid arthritis, malignancy or those receiving immunosuppressive medications or long-term OCS [Brown-Elliott et al. 2006].

Nocardiosis is normally recognized in an immunocompromised host with only occasional reports of this infection in immunocompetent patients [Menendez et al. 1997]. Even less common is occurrence of pulmonary nocardiosis in immunocompetent patients with chronic lung diseases. Aide and colleagues described a case with chronic obstructive pulmonary disease (COPD) and bronchiectasis on long-term OCS with pulmonary nocardiosis [Aide et al. 2008]. Riviere and colleagues described a case of N. cyriacigeorgica in an immunocompetent patient with COPD and bronchiectasis in whom symptoms improved with antimicrobial therapy [Riviere et al. 2011]. The authors also provided a review and identified seven additional cases of nocardiosis in patients with COPD of whom five had impaired immune response due to long-term OCS therapy and the remaining two cases were immunocompetent.

The potential mechanism for increased risk of Nocardia infection in patients with chronic lung diseases such as COPD or bronchiectasis remains unclear. It is possible that changes in pulmonary structure may result in impairment in bronchial defence predisposing to recurrent infections requiring repeated courses of antibiotics or corticosteroids [Riviere et al. 2011]. CRP is a good inflammatory marker, although the specificity and sensitivity has limitations [Patil et al. 2012]. Moreover, in our case these were normal possibly due to the prior courses of antibiotics the patient was prescribed. In such cases, would a test such as procalcitonin be a better marker of infection than CRP [Patil et al. 2012]?

There is increasing interest in identifying the airway microbiome in patients with COPD with a view to detecting co-infections quickly, thus enhancing patient care [Thurston et al. 2012]. Tests such as matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF) have proved to be quick and efficient in identifying a diverse bacterial range in COPD patients [Thurston et al. 2012]. The use of MALDI-TOF may have proved useful in our patient. Of note, in our case one may consider the use of regular antibiotics and significant airway disease as a state of relative immunodeficiency, although our patient was well controlled with her condition for at least 2 years needing no extra rescue antibiotic courses or maintenance OCS therapy.

Our case highlights the importance of considering atypical pulmonary infections such as nocardiosis in immunocompetent patients with chronic lung diseases who are unresponsive to antibiotics. Close collaboration between physicians, radiologists and microbiologists is essential in diagnosing and treating such atypical pulmonary infections.