Cultures tend to be more sensitive, but the turnaround time of several weeks significantly
diminishes their usefulness in the critical care setting. However, even if the results may not be
available in time before treatment decisions have to be made, it is extremely important to
procure tissue/fluids as positive cultures are prerequisite for later drug-susceptibility testing.
Although blood cultures in miliary TB are most likely to be positive in HIV-infected
patients, mycobacterial blood cultures are a rapid and minimally invasive method of diagnosis.
All specimens should be inoculated into an automated radiometric detection system,
preferably using lysis centrifugation techniques, which is both more rapid and more sensitive
than standard techniques using solid medium for the isolation ofM. tuberculosis. Nucleic acid
probes have been developed that can differentiateM. tuberculosisfrom commonly isolated
nontuberculous mycobacteria directly from liquid culture media.
Rapid Testing
Enzyme-linked immunosorbent assays (ELISA) capable of detecting mycobacterial antigens,
antibodies, and immune complexes have been used for diagnosis of miliary TB, but the true
usefulness of serodiagnostic tests remains to be established.
The United States Food and Drug Administration (FDA) has approved several nucleic
acid amplification tests (NAATs) for the rapid identification ofM. tuberculosisin respiratory
samples. These tests produce results within two to seven hours after sputum processing and
are therefore of interest in critically ill patients. NAATs should be performed in biosafety
level II or III laboratories. False-positive or false-negative results occur more frequently when
technician proficiency is suboptimal. While sensitivity and specificity are somewhat depen-
dent on pretest probability, all available tests perform better in smear-positive samples than in
smear-negative patients. Not a single study has evaluated the usefulness of NAATs for the
diagnosis of patients with miliary TB.
Target amplification using the polymerase chain reaction (PCR) has been more sensitive
than standard techniques in some series examining respiratory specimens, bone marrow or
liver biopsy specimens, CSF, or blood (54–57).
Molecular rapid tests have generally replaced adenosine deaminase and interferon-
gamma-based tests that have mostly been evaluated in resource-limited settings with high
pretest probabilities. Although molecular diagnostic tests can support the diagnosis of miliary
TB in the appropriate clinical setting, a negative test cannot rule out miliary TB and treatment
or additional diagnostic tests should not be delayed because of negative results.
Histopathology of Tissue Samples
Histopathologic examination of tissues continues to play an important role in the rapid
diagnosis of miliary TB. Liver biopsies have the highest yield. In the two modern case series,
granulomas were demonstrated in up to 100% of liver biopsies, 82% of bone marrow biopsies,
and 72% of transbronchial biopsies (24,33). Lymph nodes and serosal biopsies also had high
yields in these series. If biopsies were guided by clinical or laboratory abnormalities specific to
Table 2 Frequency of Positive Smear or Culture Results in Patients with Miliary TB
Specimen
Percentage of positive testsMaartens, 1990 (33) Kim, 1990 (24)Smear Culture Smear CultureSputum 33 62 36 76
BAL 27 55 9 54
CSF 8 60 0 0
Urine 14 33 7 59
Gastric aspirate 43 100 0 55
Serosal 6 44 0 14
Abbreviations: BAL, bronchoalveolar lavage; CSF, cerebrospinal fluid; TB, tuberculosis.
426 Albrecht