Abstract
To differentiate cavitary lung lesions caused by melioidosis and tuberculosis is challenging, especially in endemic countries. A study with a matched-sampling method (16 cavitary pulmonary melioidosis vs. 16 cavitary pulmonary tuberculosis) showed characteristics of bacterial infection more obvious and severe in the melioidosis patients, which were useful to distinguish two conditions.
Introduction
Cavitary lung lesions have a diversity of aetiology; some are due to bacterial infection, some to non-infectious conditions such as malignancies and autoimmune diseases. 1 Both pulmonary tuberculosis (PTB) and melioidosis induced by Burkholderia pseudomallei are infectious diseases. A study in northern Thailand reported 26% of 183 pulmonary melioidosis cases presenting as cavitary lesion and this rate increased to 50% and 68% for sub-acute/chronic pulmonary melioidosis without sepsis, respectively. 2 It is difficult to distinguish the two pathogens,3,4 as definite diagnosis depends on the microbiology. 5 Meanwhile, the culture and isolation of B. pseudomallei often take several days. Clinical clues to differentiate the two conditions in hospitalized patients are therefore useful.
Methods
We conducted a study with a matched-sampling method at the respiratory department of a large tertiary hospital from June 2019 to December 2020. A patient with pulmonary melioidosis was matched with another patient with PTB, both being of the same sex and age, cavitary lung lesions, confirmed by a radiologist and a respiratory specialist with at least 5 years of experience, according to the recommendations described. 6 PTB was diagnosed if (1) a positive smear for acid-fast bacillus and/or polymerase chain reaction for M. tuberculosis positive in specimens (sputum, bronchial lavage, or fluid of gastric aspiration) or (2) there was histopathological evidence on bronchoscopic biopsy of tuberculosis. Pulmonary melioidosis was confirmed if B. pseudomallei was isolated in specimens (sputum, bronchial lavage fluid, blood, or wound fluid).
The process for culture of B. pseudomallei was performed according to the recommendations of the American Society of Microbiology. 5 Sheep blood agar, MacConkey agar, and Chocolate agar were used to culture this pathogen. Its identification included several steps: firstly observing the bacterial colonies on the culture agars to detect the suitable characteristics of B. pseudomallei (cream colour, dry wrinkled colonies, and “safety pin” appearance on Gram staining), secondly using the automatic system (VITEK-2) to identify B. pseudomallei, and finally confirming B. pseudomallei with the 3-disc test (colistin, penicillin, and amoxicillin/clavulanic acid) which distinguishes it from other pathogens (e.g. Pseudomonas aeruginosa, Burkholderia cepacia).
Results
We collected 16 cases of pulmonary melioidosis with cavitary lesions, matched against 16 of PTB. Comparison of characteristics between the two groups is showed in table 1, including the laboratory results documented at admission. All melioidosis subjects had acute/sub-acute course (duration of initial symptoms ≤ 8 weeks). Diabetes mellitus, a common risk factor for developing melioidosis, appeared in 13 (81.3%) cases of pulmonary melioidosis. Other comorbidity found was chronic obstructive pulmonary disease in one, and alcoholic cirrhosis in another. Cavitating pulmonary melioidosis requiring hospital admission was predominant in males, 38–63 years of age, and commonly with upper lobe involvement. Melioidosis subjects presented fever more frequently and haemoptysis less than those with PTB. Likewise, they also had more severe bacterial infection than through features such as the lower level of serum sodium, the elevated liver enzymes, and the higher level of infectious markers including C-reactive protein (CRP) and neutrophil to lymphocyte ratio (NLR).
Comparison of characteristics between pulmonary melioidosis and pulmonary tuberculosis with cavitary lesion.
*Chi-squared test; !Mann-Whitney U-test; #Student's t-test IQR: interquartile range; NEU: neutrophil; NLR: neutrophil to lymphocyte ratio; SD: standard deviation.
Discussion
Radiologic findings of pulmonary melioidosis include focal consolidation or multiple nodular opacities or multiple patches of alveolar infiltration which tend coalescence and cavitation relating to infected necrosis. 4 Cavitary lung lesion occurs among patients not only with acute/sub-acute melioidosis pneumonia but also with chronic melioidosis pneumonia but increased morbidity and mortality in the acute/ sub-acute group. Clinical features of patients with cavitating pulmonary melioidosis in our study were similar to previously published melioidosis study. 4
Melioidosis and tuberculosis could present similarly many clinical scenarios such as pulmonary disease, abscess occurring one or multi organs, lumbar spondylitis, and pericarditis.3,7 Particularly, respiratory manifestation is the most common to the two conditions and even the same tendency causing cavitary lesion in the upper lobe (Figure 1) which was also reported in our study. Thus, misdiagnosis of cavitating pulmonary melioidosis as PTB is not uncommon. 8 Together with the current COVID-19 pandemic, a diagnostic approach to cavitating lung lesions is more complicated because of the increasing incidence of cavitary lesions among COVID-19 patients. 9 Its proper pathogenesis is not clear but may relate to the secondary bacterial infection, pulmonary embolism and infarction, or necrosis of parenchymal cells.
Cavitary lung lesion in the right upper lobe. A) Chest radiograph in a patient with melioidosis. B) Chest radiograph in a patient with tuberculosis.
Cavitating pulmonary melioidosis presents the broad spectrum of respiratory symptoms mimicking cavitating PTB. A 2008 study emphasized suspicion of melioidosis in diabetes mellitus patients who had fever, high erythrocyte sedimentation rate, and high neutrophil count. 3 Fever in melioidosis patients showed more frequently in our study despite no difference white blood cells, even the neutrophil count. Instead, the NLR or the CRP level were useful to discern the two conditions. Thus, fever should be considered in the appropriate clinical setting to detect early cavitating pulmonary melioidosis.
The NLR has been suggested as an inflammatory marker to evaluate severity of community acquired pneumonia (CAP). Besides, previous evidence showed its usefulness in discriminating bacterial CAP from PTB relating to pathogenesis of neutrophilia and cell-mediated immunity, respectively. 10 Hence, we recommend using NLR to differentiate melioidosis and tuberculosis in patients with cavitary lung lesion. Moreover, detecting a skin wound which could suggest an infection entry is also an important clue to suspect melioidosis.
Melioidosis pneumonia including cavitating pulmonary melioidosis is a severe infectious illness with high mortality. 4 In contrast, PTB patients often present the ambiguous features of bacterial infection. Evaluating the severity of disease through clinical symptoms, serum sodium, liver enzymes, and infectious markers helps to differentiate the two conditions.
In conclusion, melioidosis often presents characteristics of bacterial infection more obvious and severe than tuberculosis among hospitalized patients with cavitary lung lesions. These characteristics including fever, high NLR, high CRP level, low serum sodium, and elevated liver enzymes could be useful to differentiate between melioidosis and tuberculosis in clinical practice.
Footnotes
Acknowledgements
We acknowledge the contribution of Dr Truong-Thien Phu, chief of microbiology department, and Dr Le-Phuong Mai, a medical doctor of microbiology department, Cho Ray hospital, Vietnam for their continued support in identifying patients with tuberculosis and melioidosis.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
