Mr. X, a 59-year-old male, presented to the OPD with complaints of cough for 2 years which was increased in intensity for past 6 months, aggravated while lying down, associated with sputum production which was scanty, muco-purulent, green colored, not foul smelling, not blood stained and he complained of breathlessness for 6 months (MMRC Grade III). He reported history of weight loss, decreased appetite and fatigue. He denied history of fever with chills and rigors, evening rise of temperature, chest pain, sweating, palpitations, nausea, vomiting, abdominal pain, headache, visual disturbances, dysuria, hematuria and increased frequency of micturition. He has a past history of Hodgkins Lymphoma treated with 6 cycles of chemotherapy, history of Old PTB treated with ATT. He was managed outside on OPD basis with suspicion of TB reactivation, sputum cultures, sputum smear for AFB and Gene-Xpert done two times without yielding any positive result. Viral Serology was done and found to be negative. Hence he was admitted and planned for Bronchoscopy with BAL for further evaluation.
ON EXAMINATION: Conscious, oriented, afebrile, poorly built and nourished. No pallor, no icterus, no cyanosis, no clubbing, no generalized lymphadenopathy, no pedal edema. CVS- S1S2+ ; RS- BAE+, Crepitations heard over B/L Lung fields ; CNS- NFND ; P/A- Soft, Non-tender, BS+
VITALS: BP- 100/60 mmHg; PR- 110/min; RR- 24/min; SpO2- 95% with Room air; Temp- 98 F; CBG- 105mg/dl
INITIAL INVESTIGATIONS: Hb- 11.1; Hct- 35.1; WBC- 7990(71.6/12.8/14.3/0.9); ESR- 120; Plt- 4,27,000; LFT and RFT within normal limits; Urine R/E- Normal
HRCT Chest- Cystic bronchiectatic changes in bilateral upper and right middle lobes and superior segment of both lower lobes. There is surrounding fibrotic strands in the cavities of both upper lobes. Cylindrical bronchiectatic changes seen in both lower lobes. Centrilobular nodules in tree-in-bud pattern, few coalescing to patchy consolidation seen in both lower lobes(right more than left). Patchy consolidation seen in apical segment of right upper lobe.
He was started on broad spectrum IV antibiotics and other supportive medications. Bronchoscopy was done which showed purulent secretions in bilateral main and secondary bronchi, bronchus dilated and appears distorted, no endobronchial lesions. Bronchoalveolar lavage was done and samples were sent for CBNAAT, PAN Cultures, Modified ZN Stain, AFB smear, KOH Stain, Cytology. On Day 3 of IP admission, patient developed hypotension, tachycardia and he showed desaturation, hence was shifted to IMCU and was given hemodynamic support and 2L/min Nasal O2. On repeat investigations, his total leukocyte count was 19300, ECHO showed Global hypokinesia of LV with anterior wall more hypokinetic and severe LV dysfunction with EF-20%, Trop I was positive(with value of 0.33, repeat after 6 hrs showed decreased value of 0.19), ECG showed sinus tachycardia without ST/T changes. Hence, Myocardial Infarction was ruled out and a diagnosis of Stress Induced Cardiomyopathy was made and was started on T.Ivabradine 10mg BD. BAL Smear with Modified Ziehl Neelson stain showed Gram Positive Acid Fast Bacilli with branching filaments, Growth of Nocardia was noted in the BAL Culture.
Hence a diagnosis of Pulmonary Nocardiosis was made and he was started on IV Imipenem 1g BD and T. Trimethoprim-sulfamethoxazole(10-20 mg/kg of TMP and 50-100 mg/kg of SMX per day) according to guidelines. Repeat ECHO showed improvement in LV Systolic Function with EF~45-50%. He was weaned of the hemodynamic support and shifted to ward, where serial monitoring of total leukocyte count was done which showed a decreasing trend and clinical improvement was seen. Hence patient was discharged with advice to continue T. Trimethoprim-Sulfamethoxazole for 12 months with regular review in OPD. After discharge BAL AFB Culture showed growth of Non-Tuberculous Mycobacteria on 13th day. NTM/MOTT Species identification by MALDI-TOF was done and it was identified as Mycobacterium abscessus. Planned to start on appropriate antibiotics based on Drug susceptibility testing results during review.
When we received this patient in the OPD, his main concern was non-resolution of symptoms despite several course of oral antibiotics and multiple sputum cultures done without leading to the exact diagnosis. Hence Bronchoscopy with Bronchoalveolar lavage was considered and BAL samples were sent for the above mentioned investigations, which eventually lead to diagnosis of Pulmonary Nocardiosis with Mycobacterium abscessus Co-infection. When appropriate treatment was started according to standard guidelines, patient showed clinical improvement. This suggests that when there is no response to the usual antibiotics, history of underlying structural lung disease and history suggestive of immunocompromised state should arise a suspicion of any possible atypical lung infection.
Nocardiosis is an infectious disease caused by Nocardia that classically manifests as an opportunistic infection in immunocompromised hosts. Pulmonary nocardiosis and disseminated forms of the infection are opportunistic diseases occurring mainly in patients deficient in T cell-mediated immunity. Patients with the greatest susceptibility to this include those with solid organ transplant, hematopoietic stem cell transplant recipients, human immunodeficiency virus (HIV) infected patients, patients taking corticosteroids chronically, or patients with ongoing malignant processes.
Nocardia is a gram-positive bacillus with a branching hyphae morphology found throughout the environment in soil, decomposing vegetation, and other organic matter. It is also found in both fresh and salt water. Nocardia is typically weak acid-fast positive on microscopy with staining. Classically, Nocardia manifests as an opportunistic infection in immunocompromised hosts and can impact nearly every part of the human body including skin and skin structures, the pleural or pulmonary system, or it can be a disseminated disease impacting other organ systems.
Pulmonary Nocardiosis may present as either an acute infection, a subacute infection, or a chronic infection. It is clinically determined with the findings of inflammatory bronchial mass or pneumonia with fever, productive cough, dyspnea, or chest pain. Pulmonary disease may be complicated by cavitation, abscess formation, pleural effusion, or empyema.
Risk factors for acquiring Nocardia include the following:
Alcoholism, Chronic lung disease, Solid-organ transplant, Use of corticosteroids, Hematological malignancy, Collagen vascular disease (lupus), Renal failure, Inflammatory bowel disease, Whipple disease, HIV.
Essential evaluation when suspecting nocardiosis should include bacterial cultures of the infectious sites, skin biopsy, purulent discharge, sputum, deep abscess or pleural aspirates, and others. Nocardia is notoriously slow-growing, so suspicion should be shared with the laboratory to allow for ample growth time of up to 3 to 5 days. Additionally, blood cultures should be collected whenever a disseminated or pulmonary infection is suspected.
Imaging studies should include plain film chest radiography and CT chest for pulmonary infection. While there are no classical findings on radiography, they may show irregular nodules, cavitation, diffuse alveolar pulmonary infiltrates, lung abscess, or pleural effusion. Additional imaging should include CT or MRI of the brain to evaluate for disseminated Nocardia to the CNS. If meningeal signs are present, lumbar puncture with an evaluation of cerebrospinal fluid (CSF) should be performed.
M. abscessus complex can cause pulmonary disease, especially in vulnerable hosts with underlying structural lung disease, such as cystic fibrosis, bronchiectasis, and prior tuberculosis. M. abscessus complex pulmonary disease usually follows an indolent, but progressive, course, causing persistent symptoms, decline of pulmonary function, and impaired quality of life; however, the disease can also follow a fulminant course with acute respiratory failure. Establishing a diagnosis of pulmonary disease due to M. abscessus complex is not straightforward because isolation of M. abscessus complex from respiratory samples is not, in and of itself, diagnostic of pulmonary disease. According to guidelines published by the American Thoracic Society/Infectious Diseases Society of America in 2007, the diagnosis of M. abscessus complex pulmonary disease requires the fulfillment of clinical and microbiological criteria, such as the presence of clinical symptoms; radiographic evidence of lesions compatible with NTM pulmonary disease; appropriate exclusion of other diseases; and, in most circumstances, positive culture results from at least 2 separate expectorated sputum samples Common radiographic findings of M. abscessus complex pulmonary infection (i.e., bronchiolitis; bronchiectasis; nodules; consolidation; and, less frequently, cavities)
Pulmonary disease caused by M. abscessus complex is notoriously difficult to treat. Although there is no standard treatment, current guidelines suggest the administration of macrolide-based therapy in combination with intravenously administered antimicrobial agents; however, this regimen has been shown to have a substantial cytotoxic effect. According to the 2007 American Thoracic Society/Infectious Diseases Society of America guidelines, the treatment options remain limited with current antimicrobial agents, and M. abscessus complex pulmonary disease is still considered a chronic incurable disease.
Dr. S. Akash Kumar DNB General Medicine 1st Year Resident Kauvery Hospital, Chennai
Dr. Jayaraman K Senior Consultant, Internal Medicine Specialist and Diabetologist, Kauvery Hospital, Chennai
Dr. Anantha Subramanian Consultant Pulmonologist, Kauvery Hospital, Chennai
and the ICU Team.
