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Tuberculosis is always a possibility (even in the intensive care unit)

INTRODUCTION

Community-acquired pneumonia (CAP) requiring hospitalization is mainly caused by Streptococcus pneumoniae and respiratory viruses.(11 Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-27.) Among patients with severe CAP, including those requiring admission to an intensive care unit, additional important pathogens include Staphylococcus aureus, Gram-negative bacteria, and Legionella pneumophila.(11 Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-27.,22 Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677-86.)

Typically, Mycobacterium tuberculosis is not a pathogen that is strongly considered in patients with CAP because it is usually associated with a more protracted illness course and characteristic cavitary lesions on chest imaging. However, evidence exists that M. tuberculosis infection can, in fact, present with clinical manifestations consistent with CAP. For instance, using the Community-Acquired Pneumonia Organization database, which is a multinational cohort of adults hospitalized with CAP, our group found that of the 6,976 patients in the database, 60 (0.86%) had infection caused by M. tuberculosis.(33 Cavallazzi R, Wiemken T, Christensen D, Peyrani P, Blasi F, Levy G, Aliberti S, Kelley R, Ramirez J; Community-Acquired Pneumonia Organization (CAPO) Investigators. Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia. Eur Respir J. 2014;43(1):178-84.) In a study from Malaysia that included 346 patients older than 12 years of age who were hospitalized with CAP, M. tuberculosis was identified in 17 (4.9%) patients.(44 Liam CK, Pang YK, Poosparajah S. Pulmonary tuberculosis presenting as community-acquired pneumonia. Respirology. 2006;11(6):786-92.) In a study that included 103 patients with pneumonia presenting to the emergency room of a hospital in Bronx, NY, USA, 22 (21%) patients had infection caused by M. tuberculosis.(55 Gaeta TJ, Webheh W, Yazji M, Ahmed J, Yap W. Respiratory isolation of patients with suspected pulmonary tuberculosis in an inner-city hospital. Acad Emerg Med. 1997;4(2):138-41.) The proportion of patients with tuberculosis (TB) varied considerably among these studies, which may reflect different incidences of TB in the regions where the studies were conducted.

Clinically, it may be difficult to distinguish CAP caused by M. tuberculosis from CAP caused by other pathogens. As an example, relying solely on the chronicity of symptoms can be misleading. Slightly more than half of the patients in a cohort with respiratory infection caused by M. tuberculosis had symptoms for less than a week.(55 Gaeta TJ, Webheh W, Yazji M, Ahmed J, Yap W. Respiratory isolation of patients with suspected pulmonary tuberculosis in an inner-city hospital. Acad Emerg Med. 1997;4(2):138-41.) Similarly, while radiographic findings can definitely corroborate the suspicion of TB, one should not solely rely on imaging results to exclude TB. In our study, only one patient with M. tuberculosis infection had cavitary lesions, although in most patients, the consolidations were in the upper lobes.(33 Cavallazzi R, Wiemken T, Christensen D, Peyrani P, Blasi F, Levy G, Aliberti S, Kelley R, Ramirez J; Community-Acquired Pneumonia Organization (CAPO) Investigators. Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia. Eur Respir J. 2014;43(1):178-84.) Another study found that cavitary TB tends to be localized to the upper lobes, whereas the consolidations tend to be more evenly distributed throughout the lung lobes in tuberculous pneumonia (no cavitation).(66 Lee KM, Choe KH, Kim SJ. Clinical investigation of cavitary tuberculosis and tuberculous pneumonia. Korean J Intern Med. 2006;21(4):230-5.) In HIV-infected patients, consolidation or an interstitial pattern are common radiographic manifestations of TB.(77 Silva RM, Rosa L, Lemos RN. Alterações radiográficas em pacientes com a co-infecção vírus da imunodeficiência humana/tuberculose: relação com a contagem de células TCD4. J Bras Pneumol. 2006;32(3):228-33.)

Relevance for the intensivist

How is the above information relevant to the intensivist? Severe CAP accounts for approximately 11% of the cases of CAP requiring hospitalization.(88 Arnold FW, Wiemken TL, Peyrani P, Ramirez JA, Brock GN; CAPO authors. Mortality differences among hospitalized patients with community-acquired pneumonia in three world regions: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. Respir Med. 2013;107(7):1101-11.) Thus, the intensivist in the frontline is likely to see patients with M. tuberculosis infection that present as severe CAP. The recognition of patients at risk for M. tuberculosis infection enables early implementation of respiratory isolation, thus preventing the exposure of other people; timely diagnostic work-up of these patients, thus allowing for early diagnosis and treatment of those infected; and the avoidance of antibiotics that decrease the ability of diagnostic tests to identify M. tuberculosis. The failure to recognize a patient with CAP caused by M. tuberculosis can have serious consequences to the patient and the healthcare workers.

Role of clinical prediction rules

Because of the difficulty in differentiating infection caused by M. tuberculosis from infection caused by other pathogens on clinical grounds and the variability in practice that follows when clinical judgement alone dictates management decisions, a rational approach would be to identify risk factors that are present in patients at higher risk for M. tuberculosis infection and then systematically apply these factors to recognize those patients. To this end, our group identified 5 factors that are independently associated with M. tuberculosis infection in patients with CAP as follows: (1) hemoptysis; (2) upper lobe infiltrate localization; (3) weight loss or 10% or less of ideal body weight; (4) prior history of TB or recent exposure to TB or history of positive PPD; and (5) night sweats. A risk score representing the sum of these factors led to an area under the curve of 0.89 (95%CI 0.85 - 0.93) for the diagnosis of M. tuberculosis infection.(33 Cavallazzi R, Wiemken T, Christensen D, Peyrani P, Blasi F, Levy G, Aliberti S, Kelley R, Ramirez J; Community-Acquired Pneumonia Organization (CAPO) Investigators. Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia. Eur Respir J. 2014;43(1):178-84.) Our risk score needs to be externally and prospectively validated, but we believe that the use of a clinical prediction rule may be particularly valuable to help with the decision to place a patient in an airborne infection isolation room, a resource that is limited in most facilities.

Diagnostic work-up

In areas with high incidence of TB, we recommend a proactive diagnostic approach based on our experience. Just as the CAP guidelines recommend that patients with severe CAP be tested for Legionella pneumophila via a urinary antigen test,(99 Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.) we suggest that patients with CAP admitted to the hospital should routinely be tested for M. tuberculosis in areas with high incidence of TB. We propose that a sputum sample with smear and culture for acid-fast bacilli should be part of the routine microbiological work-up of these patients. As a matter of perspective, according to the Centers for Disease Control and Prevention a hospital with < 200 beds receiving > 3 cases of TB in a year is a medium-risk setting for transmission. A hospital with > 200 beds receiving > 6 cases a year is also considered medium risk.(1010 Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54(RR-17):1-141.)

Nucleic acid amplification tests can detect M. tuberculosis earlier than culture methods and should be viewed as a complementary test to sputum smear and culture. In the case of a positive acid-fast bacilli smear, a positive nucleic acid amplification test increases the positive predictive value for M. tuberculosis to > 95% and thus allows for earlier treatment. In the case of a negative acid-fast bacilli smear, a positive nucleic acid amplification test may justify treatment depending on the preclinical probability. Alternatively, the clinician may decide to repeat the nucleic acid amplification test. Cultures should always be obtained.(1111 Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009;58(1):7-10.)

CONCLUSION

In summary, M. tuberculosis is one of the pathogens that can cause community acquired pneumonia. Although classically associated with a more protracted course, M. tuberculosis can present in a more florid and acute fashion. The fundamental step for its recognition is the awareness by physicians that M. tuberculosis can even present as community acquired pneumonia with severe sepsis. In this context, we would like to bring to mind here what in Brazil has become known, by word of mouth, as Bethlem's law: tuberculosis is always a possibility.

  • Responsible editor: Jorge Ibrain Figueira Salluh

REFERÊNCIAS

  • 1
    Jain S, Self WH, Wunderink RG, Fakhran S, Balk R, Bramley AM, Reed C, Grijalva CG, Anderson EJ, Courtney DM, Chappell JD, Qi C, Hart EM, Carroll F, Trabue C, Donnelly HK, Williams DJ, Zhu Y, Arnold SR, Ampofo K, Waterer GW, Levine M, Lindstrom S, Winchell JM, Katz JM, Erdman D, Schneider E, Hicks LA, McCullers JA, Pavia AT, Edwards KM, Finelli L; CDC EPIC Study Team. Community-Acquired Pneumonia Requiring Hospitalization among U.S. Adults. N Engl J Med. 2015;373(5):415-27.
  • 2
    Torres A, Sibila O, Ferrer M, Polverino E, Menendez R, Mensa J, et al. Effect of corticosteroids on treatment failure among hospitalized patients with severe community-acquired pneumonia and high inflammatory response: a randomized clinical trial. JAMA. 2015;313(7):677-86.
  • 3
    Cavallazzi R, Wiemken T, Christensen D, Peyrani P, Blasi F, Levy G, Aliberti S, Kelley R, Ramirez J; Community-Acquired Pneumonia Organization (CAPO) Investigators. Predicting Mycobacterium tuberculosis in patients with community-acquired pneumonia. Eur Respir J. 2014;43(1):178-84.
  • 4
    Liam CK, Pang YK, Poosparajah S. Pulmonary tuberculosis presenting as community-acquired pneumonia. Respirology. 2006;11(6):786-92.
  • 5
    Gaeta TJ, Webheh W, Yazji M, Ahmed J, Yap W. Respiratory isolation of patients with suspected pulmonary tuberculosis in an inner-city hospital. Acad Emerg Med. 1997;4(2):138-41.
  • 6
    Lee KM, Choe KH, Kim SJ. Clinical investigation of cavitary tuberculosis and tuberculous pneumonia. Korean J Intern Med. 2006;21(4):230-5.
  • 7
    Silva RM, Rosa L, Lemos RN. Alterações radiográficas em pacientes com a co-infecção vírus da imunodeficiência humana/tuberculose: relação com a contagem de células TCD4. J Bras Pneumol. 2006;32(3):228-33.
  • 8
    Arnold FW, Wiemken TL, Peyrani P, Ramirez JA, Brock GN; CAPO authors. Mortality differences among hospitalized patients with community-acquired pneumonia in three world regions: results from the Community-Acquired Pneumonia Organization (CAPO) International Cohort Study. Respir Med. 2013;107(7):1101-11.
  • 9
    Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM Jr, Musher DM, Niederman MS, Torres A, Whitney CG; Infectious Diseases Society of America; American Thoracic Society. Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults. Clin Infect Dis. 2007;44 Suppl 2:S27-72.
  • 10
    Jensen PA, Lambert LA, Iademarco MF, Ridzon R; CDC. Guidelines for preventing the transmission of Mycobacterium tuberculosis in health-care settings, 2005. MMWR Recomm Rep. 2005;54(RR-17):1-141.
  • 11
    Centers for Disease Control and Prevention (CDC). Updated guidelines for the use of nucleic acid amplification tests in the diagnosis of tuberculosis. MMWR Morb Mortal Wkly Rep. 2009;58(1):7-10.

Publication Dates

  • Publication in this collection
    Apr-Jun 2016

History

  • Received
    21 Jan 2016
  • Accepted
    23 Feb 2016
Associação de Medicina Intensiva Brasileira - AMIB Rua Arminda, 93 - Vila Olímpia, CEP 04545-100 - São Paulo - SP - Brasil, Tel.: (11) 5089-2642 - São Paulo - SP - Brazil
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