While the data suggest that this approach is successful in the era of potent bactericidal regimens,
it is important to individualize the regimens in specific circumstances. Longer therapy should,
for instance, be considered in certain patients with miliary TB, including children and
immunocompromised hosts. The American Academy of Pediatrics advocates nine months of
treatment in their guidelines (59). In the presence of associated TB meningitis, treatment
duration needs to be extended to at least 12 months. In view of the high frequency of TB
meningitis in patients with miliary TB, the British Thoracic Society suggests that all patients with
miliary TB undergo a lumbar puncture in order to determine the optimal duration
of treatment (60). Patients with lymphadenitis, a large organism burden, and those with a
slow microbiologic or clinical response also tend to have a higher relapse rate and may benefit
from prolonged therapy but no evidence-based recommendations are available for such
circumstances.
The guidelines clearly recommend directly observed therapy (DOT) as the best way to
assure completion of appropriate therapy (58).
Close monitoring of patients in the intensive care unit is more important than in other
inpatient or outpatient settings. Especially in nonresponsive patients in critical care it is
important to coadminister vitamin B 6 (pyridoxine) with INH therapy in order to avoid INH
neuropathy. INH can also cause liver toxicity and cytopenias, which may be synergistic with
other toxicities or comorbidities in critically ill patients. Rifampin is a strong inducer of
cytochrome P450 metabolism. It is imperative to review all other drugs in patients on RIF in
order to anticipate potentially serious drug–drug interactions. Hypersensitivity reactions
(fever, rash) and liver toxicity are other important side effects that require constant monitoring,
especially in critically ill patients. Ethambutol can cause irreversible optic neuritis.
Adjunctive Therapy
Corticosteroids
Several randomized controlled trials and reviews have addressed the role of corticosteroids in
patients with various forms of extrapulmonary TB, such as TB meningitis, pericardial TB, and
pleural TB. No study has specifically evaluated the role of adjunct corticosteroid treatment in
patients with miliary TB. Current recommendations are based on limited evidence, further
hampered by conflicting results. A beneficial response was observed in some studies, but not
in others (61,62).
Presence of associated adrenal insufficiency is an absolute indication for corticosteroid
use. Adjunctive corticosteroid treatment may be beneficial in miliary TB with TB meningitis,
large pericardial or pleural effusion, IRD, ARDS, immune complex nephritis, and
histiocyticphagocytosis. Recent reviews have summarized the evidence for adjunctive
corticosteroids in the treatment of tuberculous pericarditis, meningitis, and pleural effusion.
These reviews have shown improved mortality for patients with pericarditis and meningitis.
While clinical parameters improved more rapidly in patients with pleural effusion, steroids
were not associated with any lasting improved outcomes for such patients (63,64).
Drotrecogin Alfa
Only one case report using activated drotrecogin alfa in miliary TB is available in the literature
(65). Decisions to use this compound will have to be based on generally approved indications
for this treatment adjunct.
Supportive Therapy
Patients with miliary TB often behave like patients in septic shock. Treatment can further
paradoxically worsen the intense cytokine release and the associated multiorgan failure either
through release of intracellular antigens from dying tubercle bacteria or reversal of TB-induced
immunosuppression causing IRD. Treatment-induced side effects can aggravate comorbidities
or drug effects commonly encountered in critically ill patients. Drug–drug interactions can be
difficult to manage in patients on rifampin-containing regimen. Collectively, these patients
tend to be complicated, at high risk for mortality, and therefore require intensive
multidisciplinary supportive therapy.
428 Albrecht