Detection of drug-resistant Mycobacterium tuberculosis in pericardial fluid culture and its correlation with cartridge based nucleic acid amplification test and adenosine deaminase activity

Abstract

BackgroundPericardial effusion is the accumulation of fluid in the pericardial cavity. In nations with high tuberculosis (TB) load, TB is the most common cause of pericardial effusion. 1–2% of patients with pulmonary TB develop Pericardial TB worldwide. Multi-drug-resistant (MDR) TB, including extrapulmonary TB (EPTB) cases, are rising in number. Adenosine Deaminase (ADA) is an enzyme in lymphocytes and myeloid cells, which has certain immune functions in the body. ADA levels are increased in inflammatory conditions, like pleural, pericardial, or joint effusions, of bacterial etiology, granulomatous conditions, neoplasms, and autoimmune pathologies. TB is the only lymphocytosis involving disease with increased ADA levels. MDR EPTB is rare, but cases are on the rise, and tuberculous pericardial effusion is one such example. Hence, it is important to know the percentage of cases detected by a culture that can be identified by cartridge-based nucleic acid amplification test (CBNAAT), their resistance patterns, and to identify potential markers like ADA, which can help in early identification of cases. The objectives of this study were to identify the Mycobacterium tuberculosis (MTB) bacilli in culture, and correlate them with cartridge-based nucleic acid amplification test (CBNAAT) results and their drug-resistance, in the Pericardial tubercular effusion, and to find if Adenosine Deaminase (ADA) levels can be used as a predictor of the presence of MTB in pericardial fluid. MethodologyWe enrolled 52 patients with moderate to large tuberculous pericardial effusion, based on pericardial fluid analysis, CBNAAT, and culture methods, between January 2021 and December 2021. ResultsThe mean age of the patients was 41.85 + 17.88 years, with a median of 38 years. Males made up 57.7% of the total patients. MTB was detected in 16 (30.8%) patients in the CBNAAT evaluations. 14 (87.5%) of the CBNAAT-positive TB patients were sensitive to Rifampicin, whereas the remaining 2 (12.5%) were resistant to Rifampicin on CBNAAT. MTB was found to be growing in 8 (15.38%) drug sensitivity test cultures. Out of these 8, 6 were sensitive to first-line drugs, whereas 2 were resistant to both Isoniazid and Rifampicin. The presence of cough was found to have a significant difference between CBNAAT-detected MTB positive and negative patients (p = 0.020), whereas an insignificant difference was found for the presence of hypertension, diabetes mellitus, obesity, dyspnea, or fever. There was also an insignificant difference between the number of patients positive for the Tuberculin skin test, between the two groups. ADA was significantly higher in the MTB-detected CBNAAT group (85.91 + 37.60U/L vs 39.78 + 24.31U/L, p = 0.005), whereas the total leukocyte count, lymphocytes, neutrophils, random blood sugar levels, and serum protein levels had no significant difference. The area under the Receiver Operator Curve (CBNAAT positive: dependent variable; ADA: test result variable) was 0.854 (null hypothesis rejected), with a standard error of 0.078. ConclusionsCulture is the gold standard method to diagnose tuberculosis. Detection of MTB on pericardial fluid culture is very uncommon, though in our study, culture came out positive in 16% of patients, and 4% were resistant to rifampicin and isoniazid. Higher ADA levels in pericardial fluid are an indicator of tuberculous pericardial effusion.