Pulmonary Nocardiosis With Endobronchial Involvement Caused by Nocardia araoensis

We report a rare case of pulmonary nocardiosis with endobronchial involvement caused by Nocardia araoensis. A 79-year-old man with a history of asthma and a previous right upper lobectomy for lung cancer and organizing pneumonia presented with cough and dyspnea. He presented with right bronchial stenosis associated with various mucosal lesions, including ulcerative and exophytic lesions. N araoensis was detected in sputum samples collected via bronchoscopy. The mucosal lesions improved after a 2-week course of meropenem. After a further 6 months of oral sulfamethoxazole-trimethoprim treatment, the mucosal lesions completely disappeared. Based on bronchoscopic and pathophysiologic findings, the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement. Nocardiosis should be considered in the differential diagnosis of endobronchial mucosal lesions. We report a rare case of pulmonary nocardiosis with endobronchial involvement caused by Nocardia araoensis. A 79-year-old man with a history of asthma and a previous right upper lobectomy for lung cancer and organizing pneumonia presented with cough and dyspnea. He presented with right bronchial stenosis associated with various mucosal lesions, including ulcerative and exophytic lesions. N araoensis was detected in sputum samples collected via bronchoscopy. The mucosal lesions improved after a 2-week course of meropenem. After a further 6 months of oral sulfamethoxazole-trimethoprim treatment, the mucosal lesions completely disappeared. Based on bronchoscopic and pathophysiologic findings, the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement. Nocardiosis should be considered in the differential diagnosis of endobronchial mucosal lesions. Pulmonary nocardiosis shows nonspecific symptoms and imaging findings, necessitating appropriate microbiological and histopathologic examinations to confirm diagnosis1Traxler R.M. Bell M.E. Lasker B. Headd B. Shieh W.J. McQuiston J.R. Updated review on Nocardia species: 2006-2021.Clin Microbiol Rev. 2022; 35e0002721Crossref Scopus (17) Google Scholar and differentiate from other conditions.2Amamiya R. Kiyoshima M. Kaburagi T. Asato Y. A new classification of bronchoscopic findings to help analysis.The Journal of the Japan Society for Respiratory Endoscopy. 2011; 33: 284-289Google Scholar Reports on nocardiosis-induced endobronchial lesions remain scarce.3Cakir E. Buyukpinarbasili N. Ziyade S. Selcuk-Duru H.N. Bilgin M. Topuz U. Endobronchial nocardiosis in an 11-year-old child.Pediatr Pulmonol. 2013; 48: 1144-1147Crossref Scopus (4) Google Scholar,4Ohya M. Nakamura Y. Yoshida M. et al.A case of nocardiosis with associated endobronchial excavated lesions.Kansenshogaku Zasshi. 2012; 86 ([in Japanese]): 592-596Crossref Scopus (2) Google Scholar We report a rare case of pulmonary nocardiosis with endobronchial involvement caused by Nocardia araoensis. A 79-year-old man who did not use tobacco presented with cough and dyspnea for 1 month. He had received inhaled corticosteroid (ICS) therapy for 12 years for bronchial asthma and had undergone a partial right upper lobectomy for non-small cell lung cancer (papillary adenocarcinoma) pT1bN0 pStage IA2 11 years prior. Additionally, the residual right upper lobe and mediastinal lymph nodes (ND2a-2) had been resected 1 year before admission because of suspected cancer recurrence. Histology revealed organizing pneumonia without signs of cancer. No systemic steroid therapy was administered. Physical examination indicated an elevated respiratory rate and right chest wheezing. Blood biochemistry indicated mild inflammation, with a C-reactive protein level of 2.33 mg/dL and an erythrocyte sedimentation rate of 43 mm/h. His FEV1/FVC ratio was low (54.5%), suggesting airway hyperreactivity. Contrast-enhanced CT scan showed a contrast-enhancing effect around the right main bronchus (Fig 1A) and 10-mm and 15-mm nodules in the right middle and left lower lobes, respectively (Fig 1B, C). PET-CT scan showed increased fluorodeoxyglucose uptake (maximum uptake value, 9.3) around the right main bronchus (Fig 1D). Bronchoscopy showed ulcerative mucosal lesions (Fig 2Aⅰ, Aⅱ) and exophytic papillary lesions involving the surgical anastomosis site, causing right bronchial stenosis (Fig 2aⅲ). Exophytic lesions were examined via biopsy, and intrabronchial sputum samples were collected because the different types of mucosal lesions suggested malignancy, infection, or both. Gram-positive filamentous bacilli were detected in a sputum smear; the sample was forwarded to a reference microbiology laboratory (SRL, Inc., Kumamoto, Japan) to confirm suspected nocardiosis. Although the biopsy tissue showed no evidence of malignancy, the possibility of malignancy elsewhere in the lung could not be excluded.Figure 2Bronchoscopy findings on admission (A), 2 weeks after meropenem treatment (B), and 2 months after sulfamethoxazole-trimethoprim treatment (C), with improvements in ulcerative mucosal lesions spreading from the right side of the trachea to the right main bronchus (ⅰ, ⅱ) and exophytic papillary lesions from the right main bronchus to the middle bronchus trunk with bronchial stenosis (ⅲ), and postoperative stump without surrounding abnormal findings (ⅳ).View Large Image Figure ViewerDownload Hi-res image Download (PPT) The patient was hospitalized for antibiotic therapy and rebiopsy. Meropenem (1 g) was administered at 8-h intervals, and ICS therapy was discontinued. No additional antibiotics were prescribed because of poor renal function. His symptoms improved markedly within 2 weeks, with C-reactive protein and erythrocyte sedimentation rate reduced to 0.20 mg/dL and 22 mm/h, respectively. Bronchoscopy showed reduced mucosal lesions and partial resolution of the bronchial stenosis (Fig 2B). N araoensis was identified by matrix-assisted laser desorption ionization time of flight mass spectrometry, with the broth microdilution antimicrobial susceptibility method confirming susceptibility to sulfamethoxazole/trimethoprim. The patient exhibited improved renal function after hydration and sufficient rest. Oral sulfamethoxazole/trimethoprim therapy (2,400 mg/480 mg/day) was administered and subsequently reduced to 1,600 mg/320 mg/day based on renal function. Two months later, a final confirmatory bronchoscopy showed no endobronchial lesions (Fig 2Cⅰ-ⅲ); the postoperative stump was confirmed (Fig 2Cⅳ), with no lung nodules or evidence of cancer on CT. Based on the absence of other microbiological findings (eg, fungi or mycobacteria), the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement. The patient resumed ICS and completed a 6-month sulfamethoxazole/trimethoprim therapy, with no recurrence of nocardiosis observed over the next 18 months. In nocardiosis, certain species are primarily associated with lung infections, whereas others, such as Nocardia brasiliensis, are primarily associated with cutaneous infections.1Traxler R.M. Bell M.E. Lasker B. Headd B. Shieh W.J. McQuiston J.R. Updated review on Nocardia species: 2006-2021.Clin Microbiol Rev. 2022; 35e0002721Crossref Scopus (17) Google Scholar,5Brown-Elliott B.A. Brown J.M. Conville P.S. Wallace Jr., R.J. Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy.Clin Microbiol Rev. 2006; 19: 259-582Crossref PubMed Scopus (0) Google Scholar N araoensis has been identified in the sputum of patients with nontuberculous mycobacterial disease.6Kageyama A. Yazawa K. Mukai A. et al.Nocardia araoensis sp. nov. and Nocardia pneumoniae sp. nov., isolated from patients in Japan.Int J Syst Evol Microbiol. 2004; 54: 2025-2029Crossref Scopus (29) Google Scholar Its clinical characteristics remain unclear, with limited case reports of cutaneous infections7Akasaka E. Ikoma N. Mabuchi T. et al.A novel case of nocardiosis with skin lesion due to Nocardia araoensis.J Dermatol. 2011; 38: 702-706Crossref Scopus (6) Google Scholar,8Sasaki R. Mochida K. Koketsu H. et al.Cutaneous nocardiosis associated with Isaacs' syndrome.Hifuka no Rinsho. 2018; 60: 1138-1141Google Scholar and meningitis.9Yamamoto F. Yamashita S. Kawano H. et al.Meningitis and ventriculitis due to Nocardia araoensis infection.Intern Med. 2017; 56: 853-859Crossref PubMed Scopus (0) Google Scholar,10Joshua S. Babu R. Warrier A. Panikar D. Nocardia araoensis causing brain abscess.Asian J Neurosurg. 2019; 14: 952-956Crossref PubMed Google Scholar Endobronchial lesions are extremely rare in any Nocardia species. Among 12 cases, Ohya et al4Ohya M. Nakamura Y. Yoshida M. et al.A case of nocardiosis with associated endobronchial excavated lesions.Kansenshogaku Zasshi. 2012; 86 ([in Japanese]): 592-596Crossref Scopus (2) Google Scholar reported ulcerative lesions in only two patients, whereas other cases showed exophytic lesions. The patient showed ulcerative lesions in the area of paratracheal lymphadenectomy and exophytic lesions in an area without lymphadenectomy. Accordingly, lymphadenectomy-related differences in local immunity could underlie the distinct morphologies. Nocardiosis is commonly observed in immunocompromised patients but may occur in immunocompetent patients.11Margalit I. Lebeaux D. Tishler O. et al.How do I manage nocardiosis?.Clin Microbiol Infect. 2021; 27: 550-558Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Moreover, ICS therapy has been associated with nocardiosis.12Cascarano E. Frappa M. Degano B. Pelloux I. Sant-Raymond C. Gheerbrant H. Several Nocardia abcessus bronchiolitis in a patient with treated with inhaled corticosteroids: a case report.Allergy Asthma Clin. Immunol. 2023; 19: 27Crossref Scopus (0) Google Scholar,13Woodworth M.H. Saullo J.L. Lantos P.M. Cox G.M. Stout J.E. Increasing nocardia incidence associated with bronchiectasis at a tertiary care center.Ann Am Thorac Soc. 2017; 14: 347-354Crossref PubMed Scopus (34) Google Scholar The patient was undergoing long-term ICS therapy, potentially contributing to nocardiosis development. Although initial treatment with meropenem alone and ICS discontinuation afforded clinical improvement in this case, monotherapy, especially before establishment of antimicrobial susceptibility, is not recommended for pulmonary nocardiosis.11Margalit I. Lebeaux D. Tishler O. et al.How do I manage nocardiosis?.Clin Microbiol Infect. 2021; 27: 550-558Abstract Full Text Full Text PDF PubMed Scopus (59) Google Scholar Repeat bronchoscopy, performed for suspected concomitant lung cancer, showed improvement of all lesions after antibiotic treatment; hence, the patient was diagnosed with pulmonary nocardiosis with endobronchial involvement caused by N araoensis. Nocardiosis should be considered in the differential diagnosis of endobronchial lesions. This case report illustrates the usefulness of bronchoscopy with histopathologic and microbiological investigation. None declared. Other contributions: We thank Editage (www.editage.cn) for the English language editing.