Pulmonary Nocardiosis in Chronic Obstructive Pulmonary Disease: Beyond Immunodeficiency

ABBREVIATIONS USED IN THIS ARTICLE

AFB = Acid-fast bacilli; BAL = Broncho-alveolar lavage; CBNAAT = Cartridge based nucleic acid amplification test; COPD = Chronic obstructive pulmonary disease; FEV1 = Forced expiratory volume in the first second; FVC = Forced vital capacity; HIV = Human immunodeficiency virus; PN = Pulmonary nocardiosis; ZN = Ziehl–Neelsen.

INTRODUCTION

Pulmonary nocardiosis (PN) is a rare opportunistic infection caused by nocardia species. This organism was identified by Edmond Nocard in 1888 from cattle with bovine farcy. The first human case was reported by Eppinger in 1890. The organism is commonly found in long-standing dust, soil, and stagnant water. It primarily enters the body via inhalational route, followed by direct inoculation from trauma or intravenous drug abuse, and rarely from ingestion of contaminated food. Human-to-human spread has not been reported yet.¹ The annual incidence in North America, Europe, and Australia is estimated ~0.375 cases per 100,000 persons.² Lungs are the most commonly involved organ, seen in 70% of cases of nocardiosis. Almost 50% of cases of PN have disseminated nocardiosis with the brain being the commonest site of dissemination.²

Pulmonary nocardiosis is commonly reported in immunocompromised patients, commonly including, people living with human immunodeficiency virus (HIV) infection, chronic alcoholics, diabetes mellitus, post organ transplantation, hematological neoplasms, and iatrogenic immunosuppression (by long term steroid use, chemotherapy drugs and anti-tumor necrosis factor-alpha agents).^1,3 It was found that 10–25% of cases of nocardiosis were found in immunocompetent individuals.⁴

Here, we present a case report of a 60-year-old female patient with chronic obstructive pulmonary disease (COPD) having PN. The authors obtained written informed consent from the patient.

CASE DESCRIPTION

A 60-year-old female, housewife by profession, presented to medical OPD with complaints of fever with chills and rigor for 45 days, productive cough with mucoid, whitish sputum for 1 month, dyspnea for 15 days, and chest pain for 10 days. The patient was an active smoker (20 packs/year). There was no history of evening rise of temperature, skin rashes, hemoptysis, orthopnea, paroxysmal nocturnal dyspnea, palpitations, and bladder/bowel complaints.

On examination, the patient had fever and tachypnoea. Chest movements were reduced on the right side. Chest expansion was 3 cm. On chest auscultation, air entry was reduced on the right side, bilateral rhonchi were present and the right infra-scapular and lower axillary region had coarse crepitations. The rest of the systemic examination was normal. On baseline blood investigations, the patient had a hemoglobin of 9.0 gm/dL, leukocyte count of 22800 cells/cc with 90% neutrophils, platelet count of 1.2 lakhs/dL, ESR of 50 mm/hr, Liver and kidney function tests was normal. Arterial blood gas analysis showed respiratory acidosis with compensated metabolic alkalosis. Chest X-ray were suggestive of non-homogenous opacity in the right middle and lower lung zones (Fig. 1).

Spirometry was suggestive of obstructive airway disease with 7% and 6% improvement in forced expiratory volume in the first second (FEV1) and forced vital capacity (FVC), respectively, post bronchodilator use. The patient was not on any inhalational or systemic steroid therapy. The patient was diagnosed with right middle and lower zone pneumonia. On the gram stain of sputum, only pus cells were seen, and no bacterial or fungal organism was seen. On Ziehl–Neelsen (ZN) staining of sputum, no acid-fast bacilli (AFB) was seen. No mycobacterial organism was detected on cartridge-based nucleic acid amplification test (CBNAAT) performed on sputum. Empirical antibiotic therapy was started to target common micro-organisms causing pneumonia. Blood, sputum, and urine samples were sent for culture, but no organism could be isolated. Neither clinical nor radiological improvement (on chest X-ray) was seen after 1 week of antibiotic therapy. In view of no improvement, the patient was subjected to further investigations to find out the etiology. Computed tomography chest of the patient showed collapse/consolidation with areas of cavitation in the right middle and lower lung lobes (Fig. 2).

The patient underwent bronchoscopy. Broncho-alveolar lavage (BAL) fluid on the gram stain showed only pus cells. No AFB was seen on the ZN stain of BAL fluid. Broncho-alveolar lavage fluid was inoculated on blood agar, on which, white colored colonies were isolated. Further identification of the colony was done by standard microbiological methods. Gram stain showed gram-positive thin branching filaments (Fig. 3).

On biochemical test, it was catalase-positive, Urea hydrolysis test-positive, Simmons citrate test-negative, Nitrate reduction test negative, no gelatin liquefaction and hydrolysis of casein, tyrosine, and xanthine seen. Findings were suggestive of the nocardia species. Antibiotic sensitivity test is done by Kirby Bauer disc diffusion method. The isolate was sensitive to cotrimoxazole and minocycline. Serological markers for HIV 1 and 2, hepatitis B, and hepatitis C were negative. Value of HbA1c was 6.0%. The CD4 count was 995 cells/mm³. Antinuclear antibodies and cANCA levels were normal. CT head of the patient was normal, ruling out a cerebral abscess.

Combination antibiotic therapy with cotrimoxazole double strength (160/800 mg) 1 tablet twice a day, meropenem, and amikacin was started. Meropenem and amikacin were given for 14 days. Cotrimoxazole was continued for 6 months. After 1 month, there was resolution of clinical symptoms (with decreased cough, sputum, and dyspnea), neutrophilic leukocytosis, and radiological abnormality. Repeat chest X-ray after 2 months showed improvement in lung consolidation (Fig. 4). Repeat spirometry done after 2 months confirmed the presence of COPD, with 9% and 7% improvement in FEV1 and FVC, respectively, post bronchodilator use.

DISCUSSION

Nocardial infections occur worldwide and are more prevalent in tropical and subtropical regions. Recently, more cases of nocardiosis are being reported from India. The largest series of nocardiosis was published by Shome et al., where 860 patients with pulmonary tuberculosis were studied, among which 32 were found to have PN, who were treated previously with antitubercular drugs.⁵ It is commonly seen in males. The mean age of incidence is 66 years, and can be higher in COPD patients or lower among organ transplant recipients or HIV patients.^1,2

The clinical picture of PN is highly nonspecific. It commonly presents with fever, breathlessness, cough, hemoptysis, and weight loss. Similar clinical features are also seen in pulmonary tuberculosis, invasive fungal disease, lung abscess, community-acquired pneumonia, Wegener`s granulomatosis and lung cancer. The most important differential of PN is tuberculosis. The radiological picture is also non-specific, commonly presenting as consolidations, and large irregular nodules (commonly cavitatory), however, interstitial patterns, and lung mass may also be seen.⁶ Sulphonamides remain the drug of choice for nearly all cases of nocardia. Other drugs include linezolid, minocycline, and amoxicillin + clavulanic acid. Amikacin, ceftriaxone and imipenem are parenteral drugs available for nocardia. Treatment for nocardia is usually continued for 6–12 months.²

Nocardiosis is an opportunistic infection commonly seen in immunocompromised patients but 10–25% of patients do not have any immunosuppressive condition.⁴ It is commonly seen in patients with chronic respiratory diseases, where COPD and bronchiectasis make the most of them.^1,7 COPD is one of the most common risk factors after chronic steroid therapy and solid organ transplantation. In COPD, it is found that long-term exposure to inhaled steroids and structural changes in local defense mechanisms (altered ciliary motility and epithelial damage) are possibly responsible for the relatively higher incidence of PN in these patients.⁸ This case report where the patient has COPD without respiratory failure, and was never treated with systemic or inhaled steroid therapy and had no comorbidity, further provides evidence for COPD as an independent risk factor for PN.

Pulmonary nocardiosis is a rare and challenging disease with high mortality ranging from 14 to 40% that may go up to 60–100% in patients with central nervous system involvement.^1,9 Nocardia should always be considered a possible differential diagnosis, both in immunocompromised as well as immunocompetent patients, as evident from this case report. As the symptoms, signs, and chest imaging features of nocardiosis can masquerade other diseases, like tuberculosis, a high degree of awareness among treating physicians and extensive microbiological evaluation is necessary for early diagnosis and timely initiation of life-saving treatment.

REFERENCES

1. Castellana G, Grimaldi A, Castellana M, et al. Pulmonary nocardiosis in chronic obstructive pulmonary disease. A new clinical challenge. Respir Med Case Rep 2016;18:14–21. DOI: 10.1016/j.rmcr.2016.03.004.

2. Kasper D, Fauci A, Hauser S, et al. Harrison’s Principles of Internal Medicine, 19th edition. South East Asia: McGraw-Hill Professional Publishing; 2015. pp. 1084–1087.

3. Ambrosioni J, Lew D, Garbino J. Nocardiosis. Updated clinical review and experience at a Tertiary Center. Infection 2010;38(2):89–97. DOI: 10.1007/s15010-009-9193-9.

4. Matulionyte R, Rohner P, Uckay I, et al. Secular trends of nocardia infection over 15 years in a tertiary care hospital. J Clin Pathol 2004;57(8):807–812. DOI: 10.1136/jcp.2004.016923.

5. Shome SK, Upreti HB, Singh MM, et al. Mycoses associated with pulmonary tuberculosis. Ind J Tuberc 1976;23:64–68.

6. Aggarwal D, Garg K, Chander J, et al. Pulmonary nocardiosis revisited: A case series. Lung India 2015;32(2):165–168. DOI: 10.4103/0970-2113.152638.

7. Riviere F, Billhot M, Soler C, et al. Pulmonary nocardiosis in immunocompetent patients: Can COPD be the only risk factor?. Eur Respir Rev 2011;20(121):210–212. DOI: 10.1183/09059180.00002211.

8. Maggiorelli C, Di Pierro I, Manta C, et al. Nocardia and lungs in COPD: Beyond immuno-deficiencies. COPD 2015;12(3):321–326. DOI: 10.3109/15412555.2014.933951.

9. Chedid M, Chedid M, Porto N, et al. Nocardial infections: Report of 22 cases. Rev Inst Med Trop Sao Paulo 2007;49(4):239–246. DOI: 10.1590/s0036-46652007000400009.