Abstract

1. Introduction

2. Material and Methods

3. Results

We studied 120 patients with diagnosis of acute CAP including 21 (17.5%) tuberculous and 99 (82.5%) non-tuberculous CAP. The etiologies of CAP in the latter group were as follow: S. pneumoniae 29 (29.3%), followed by S. aureus, polymicrobial including anaerobes, and other agents. The diagnosis of pneumonia remained unknown in 49 (40% of all cases) of patients. We found approximately equal gender distribution among two study groups (14/21 vs. 61/99, 63.6% vs. 62.9%, p=0.948). Patients with tuberculous CAP were younger compared with non-tuberculous patients (46.6±21 vs. 51.2±22.5) but the difference in mean age was not statistically significant (p=0.386) (Table 1). The most common presenting clinical symptoms in both groups were cough and fever, followed by dyspnea, sputum production, chest pain, and hemoptysis. However, cough (90.9% vs. 83.9%), sputum production (75% vs. 50.9%), and weight loss (45.5% vs. 8.6%) were more common in the tuberculous group (90.9% vs. 83.9%), whereas history of fever (84.8% vs. 77.3%), dyspnea (79.6% vs. 72.7%), and chest pain (19.6% vs. 13.6%) were more frequent in the non-tuberculous group. Both groups had approximately equal frequency of hemoptysis (13%). Study groups differed significantly in duration of symptoms before admission (16.5±8.8 vs. 8.1±5.1, p=0.001) that was longer in patients with tuberculous CAP. The frequency of tachypnea, hypotension, and tachycardia were not significantly different between the two groups, however, patients with non-tuberculous CAP were more commonly febrile at the time of hospital admission (85.2% vs. 47.6%, p=0.01). The frequency of high grade fever (temperature > 38.2) was also significantly higher in non-tuberculous group (80.5% vs. 47.6%, p=0.002) (Table 2). Although patients with non-tuberculous CAP were more commonly hypoxic at presentation (76.2% vs. 62.9%) the difference was not statistically significant (p=0.25). The frequency of severe hypoxia (arterial oxygen saturation <85%) was also approximately equal for both groups (47.6% and 43.7%, p=0.744). No significant difference was seen in IVRS requirement between two groups (38.1% vs. 30.5%, p=0.501). In-hospital mortality (IHM) was equal in two groups (22.9% vs. 23.7%; p=0.665). Two (1.6%) patients with CAP were diagnosed to have HIV infection. Fifty percent of patients with tuberculous CAP had opioid addiction that was more frequent compared with non-tuberculous group (p=0.240). Laboratory characteristics on admission were also compared between two groups, including the value of white blood cells count, polymorphonuclear (percent), platelet count, hematocrit level, and PCT level. Hematocrit level<36% (p=0.01) and PCT level >0.5 (p=0.001) were the only parameters that were significantly different between these two groups (Tables 3). Among patients with final diagnosis of pulmonary CAP, 8 (38.1%) cases received multidrug anti-tuberculous agents empirically in the 1st 24-hour antibiotic treatment regimen. In comparing the two study groups, there were no significant differences in severity of CAP based on pneumonia severity index (PSI) (p=0.378), Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) (p=0.800), CURB-65 (p=0.478), and SMART-COP (p=0.659) scoring systems. 52.4%, 63.2%, 30%, and 90% of patients with tuberculous CAP had severe presentation based on PSI, IDSA/ATS, CURB-65, and SMART-COP, respectively (Table 4).

4. Discussion

M. tuberculosis is an important cause of CAP in developing countries. TB can present as an acute process and mimic classic bacterial pneumonia or masquerade as an atypical pneumonia, with nonproductive cough and systemic symptoms. As such, it should be included in the differential diagnosis of CAP. Both primary and reactivation TB can cause acute manifestations (5). M. tuberculosis is an important cause of lower respiratory infection in many parts of Asia. Peto et al., (4) suggested that decisions about the choice of routine investigations performed for CAP and the choice of empirical treatment should reflect this fact. Although the use of fluoroquinolones as empirical treatment for CAP is appropriate even in regions endemic for TB, indiscriminate use of fluoroquinolones in suspected CAP should be avoided, and critical judgement on the possibility of TB should be considered in patients who present with CAP (5). Missed diagnosis is common as illustrated in a report from Baltimore in which 16 of 33 patients (48%) with culture-confirmed pulmonary TB were initially treated for presumed CAP (9). Of our patients, 17.5% were finally diagnosed as pulmonary TB that demonstrated the important role of M. tuberculosis in the etiology of CAP in our region. The incidence of TB being diagnosed among patients presenting with clinical and radiological signs of a CAP has varied in different series. Previously, studies from China, Japan, Kenya, and Sub Saharan Africa also demonstrated high prevalence of pulmonary TB (9–20.5%) in patients who presented with CAP (10–14). M. tuberculosis was the second most common pathogen (12%) identified in the study performed by Levy et al., (15) in Hong Kong. In the latter study, only patients who presented with features of acute pneumonia were included and those with chronic illness or typical radiologic changes suggestive of TB were excluded. A similar high incidence of TB (10%) among subjects presenting with acute pneumonia had been reported in France (11). In the studies by Nyamande et al., (12) in Sub Saharan Africa and Scott et al., (14) in Kenya, a large number of CAP patients were diagnosed as HIV positive (81.4% and 52%, respectively). However, in our study, only two patients were diagnosed to have HIV infection (1.6%). Of tuberculous CAP patients who were opioid addicted, there were 50%, and 23.8% of them had underlying chronic diseases. In addition to epidemiologic clues, many clinical clues have been suggested that might prompt consideration of a tuberculous etiology. These include duration of symptoms more than 2 weeks prior to admission, upper lobe involvement or cavitary infiltrates on chest radiograph, lymphopenia, total white blood cell count ≤12 × 109/l on admission, night sweats, failure to respond to routine therapy of CAP, relapse following fluoroquinolone administration, relapse following corticosteroid administration, Gram stain with weakly gram-positive or gram-neutral rods (ghosts), signs of healed TB, e.g. fibrocalcific changes, apical capping, Ghon’s complex, pneumothorax, and pleural effusion. Identification of these features at presentation, clearly strengthens the diagnostic suspicion of TB (5, 16, 17). According to the literature review performed by Grossman et al., TB is not associated with a rapid response to antimicrobial therapy even when treated with appropriate multidrug regimens. In contrast, some clinical improvement is usually seen within 2 to 3 days of appropriate antimicrobial treatment of patients with non-tuberculous CAP (5). When we compared clinical and laboratory characteristics between patients with tuberculous and non-tuberculous CAP, these two groups differed significantly in the frequency of weight loss, absence of fever on admission, anemia, and duration of symptoms before admission. High grade fever at presentation, was significantly lower among patients with pulmonary TB. Although the frequency of associated exudative pleural effusion was higher in tuberculous CAP patients, the difference was not statistically significant. PCT level does not appear to be significantly elevated in patients with pulmonary TB, making it an attractive potentially rapid diagnostic method for differentiating pulmonary TB from bacterial CAP. Although there are studies that found PCT level as an unreliable indicator for diagnosis of pulmonary TB (18), most others demonstrated that the PCT level in patients with pulmonary TB is significantly lower than patients with other etiologies of CAP (19, 20). Additionally, several studies showed that high level of PCT among patients with pulmonary TB is an indicator of adverse outcome (19, 20). In the study conducted by Kang et al., (21) the median PCT level was 0.514 ng/mL (range, 0.01 to 27.75) with bacterial CAP and 0.029 ng/mL (range, 0.01 to 0.87) with pulmonary TB. They concluded that the high sensitivity and negative predictive value for differentiating pulmonary TB from bacterial CAP, suggested a supplementary role of PCT in the diagnostic exclusion of pulmonary TB from bacterial CAP in areas with an intermediate prevalence of pulmonary TB. Our study, similarly to most others, demonstrated significantly lower PCT levels in patients with tuberculous CAP compared with the non-tuberculous group however, it was not associated with higher rates of IHM and IVRS requirement among patients with TB. PCT level was significantly associated with poor outcome and IVRS requirement in patients with other etiologies of CAP. In the study performed by Levy et al., (22) the incidence rate of 1.5% has been reported for acute respiratory failure among patients who present with tuberculous hospitalized CAP. In our study, 22.7% and 76.2% of patients with tuberculous CAP developed hypotension and hypoxia, respectively. These rates were not significantly higher compared with non-tuberculous CAP patients. Of patients with tuberculous CAP 38.1% required IVRS. Feng et al., (23) found that higher PSI scores were independently associated with the presence of concomitant pulmonary TB in both health care associated pneumonia (HCAP) and CAP patients. However, severity assessment of CAP based on pneumonia severity index (PSI), Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS), CURB-65, and SMART-COP scoring systems, showed no significant difference between our two study groups. IHM was 23.7% among tuberculous CAP patients which was higher than the non-tuberculous group.

5. Conclusions

Although pulmonary TB is known as a chronic disease, it can present as acute pneumonia. Differentiation of tuberculous from non-tuberculous CAP is an important challenge in endemic areas of TB like Iran. Regarding the fact that M. tuberculosis was the etiologic agent responsible for 17.5% of our acutely presented CAP patients, it seems rational to emphasize that the diagnosis of TB should be considered in all patients who presented with CAP in our region. It could not be differentiated from other causes of pneumonia on clinical and radiologic grounds, although patients with tuberculous CAP had significantly higher frequency of weight loss, anemia, absence of fever on admission, and longer duration of symptoms before presentation. PCT level is significantly lower among the tuberculous CAP group. This study suggested that the severity of illness is also not useful in differentiation of tuberculous from non-tuberculous CAP. Patients with tuberculous CAP had higher IHM, however, it was not statistically significant.

Acknowledgments

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