eMedicine Specialties > Infectious Diseases > Mycobacterial Infections
Miliary Tuberculosis: Treatment & Medication
Updated: Nov 16, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
Treatment
Medical Care
Early treatment of patients with suspected miliary tuberculosis (TB) decreases the likelihood of mortality and improves outcome.
Surgical Care
Surgical treatment is rarely necessary. Occasionally, a ventriculoatrial shunt is indicated for hydrocephalus.
Consultations
- Pulmonary and critical care specialists
- Infectious disease specialist
- Neurologist - Steroids for meningitis or paradoxically increasing tuberculomas
- TB expert
- Health department notification
- Appropriate infection control measures
Diet
Adequate attention to nutrition is important. Many patients with miliary TB are debilitated by the disease, and malnutrition can contribute to a weakened immune system.
Activity
Once the patient receives several weeks of effective therapy, experiences significant clinical improvement, and has negative sputum acid-fast bacillus smears, restrictions are minimal. However, one must be certain that the patient truly is no longer contagious. The absence of sputum positivity does not guarantee others protection against exposure. Directly observed therapy is optimal for assuring compliance and preventing relapse.
Medication
Early empirical therapy for suspected miliary tuberculosis (TB) is prudent. A delay of even 1-8 days contributes to a high mortality rate.
Steroids are warranted for hypotension due to presumed adrenal insufficiency after an adrenocorticotropic hormone (ACTH) stimulation test.
For susceptible organisms, the treatment period is 6-9 months. For meningitis, it is 9-12 months. For miliary TB with meningeal involvement, daily medications for the entire length of therapy are recommended.
Three basic rules apply in the prevention of entirely "doctor-made" resistant TB, which cost more than $180,000 in the United States in 1991. First, rifampin is the drug of choice for treatment. In most cases, the treatment duration is at least 18 months without rifampin. Second, ethambutol (EMB) is used to prevent rifampin resistance if the organism is resistant to isoniazid (INH). EMB can be discontinued as soon as the organism is found to be susceptible to rifampin and INH. Third, pyrazinamide is used for the first 2 months of treatment to decrease the treatment duration from 9 months to 6 months if the organism is susceptible to rifampin and INH.
For MDR-TB, use a minimum of 1 susceptible injectable and at least 3 additional susceptible drugs to prevent the development of additional resistance. Treat MDR-TB with the consultation of an expert in the care of TB.
Intermittent-type therapies have not been established. If MDR-TB test results are pending, increasing the number of drugs is reasonable. For example, use 6 or 7 initial drugs, including an injectable.
Antitubercular agents
Any regimen must contain multiple drugs to which TB is susceptible. In addition, drug therapy must be taken regularly and continued for a sufficient period.
Miliary TB has a high number (load) of organisms; thus, the initial number of medications should be high.
Rifampin (Rifadin, Rimactane)
One of most important TB drugs. Used in combination with other antituberculous drugs in the treatment of all forms of TB. Without rifampin, the treatment duration is at least 18 mo.
Inhibits DNA-dependent RNA polymerase activity in susceptible cells. Specifically, interacts with bacterial RNA polymerase but does not inhibit mammalian enzyme. Cross-resistance has been shown only with other rifamycins.
Continue therapy for 6-9 mo or until at least 6 mo have elapsed from conversion to sputum culture negativity.
Restart with different schedule if rifampin was discontinued because of adverse effects (eg, 20 min after a light meal, in divided doses).
Adult
600 mg/d IV if patient unable to tolerate PO or if reasons exist to suspect that PO medication will not achieve desired absorption
Often can be changed to 600 mg PO 2 d/wk after the first 2 wk
Pediatric
10-20 mg/kg PO/IV; not to exceed 600 mg/d
Induces microsomal enzymes, which may decrease effects of acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, oral contraceptives, corticosteroids, mexiletine, cyclosporine, digitoxin, disopyramide, estrogens, hydantoins, methadone, clofibrate, quinidine, dapsone, tazobactam, sulfonylureas, theophyllines, tocainide, and digoxin; blood pressure may increase with coadministration of enalapril; coadministration with INH may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur); hepatotoxicity and hepatic encephalopathy have been shown when rifampin and INH are given after halothane anesthesia
Documented hypersensitivity; severe thrombocytopenia (<20,000/μL)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Obtain CBC cell counts and baseline clinical chemistries prior to and throughout therapy; in liver disease, weigh benefits against risk of further liver damage; interruption of therapy and high-dose intermittent therapy are associated with thrombocytopenia that is reversible if therapy is discontinued as soon as purpura occurs; if treatment is continued or resumed after appearance of purpura, cerebral hemorrhage or death may occur
Isoniazid (Laniazid, Nydrazid)
Best combination of effectiveness, low cost, and minor adverse effects. First-line drug unless known resistance or another contraindication. Therapeutic regimens of <6 mo demonstrate unacceptably high relapse rate.
Coadministration with pyridoxine recommended if peripheral neuropathies develop secondary to INH therapy. Prophylactic doses of 6-50 mg/d of pyridoxine are recommended.
Adult
5 mg/kg/d (usually 300 mg/d) PO/IV and 10 mg/kg/d PO/IV in 1-2 divided doses in patients with disseminated disease; not to exceed 300 mg/d
In directly observed therapy, administer 15 mg/kg 2 times/wk PO/IV; not to exceed 900 mg/d
Pediatric
10-20 mg/kg/d PO/IV; not to exceed 300 mg/d
Higher incidence of INH-related hepatitis can occur with daily alcohol ingestion; aluminum salts may decrease serum levels (administer 1-2 h before taking aluminum salts); may increase anticoagulants effects with coadministration; may inhibit metabolic clearance of benzodiazepines; carbamazepine toxicity or INH hepatotoxicity may result from concurrent use (monitor carbamazepine concentrations and liver function); coadministration with cycloserine may increase adverse CNS effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram coadministration with rifampin after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin an increase in the pharmacologic or toxic effects of the hydantoins may occur
Documented hypersensitivity; previous INH-associated hepatic injury or other severe adverse reactions
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during therapy are recommended even when visual symptoms do not occur
Pyrazinamide
Pyrazine analog of nicotinamide that may be bacteriostatic or bactericidal against M tuberculosis, depending on concentration of drug attained at site of infection; mechanism of action is unknown.
Administer for initial 2 mo of a 6-mo or longer treatment regimen for drug-susceptible cases. Treat drug-resistant cases with individualized regimens.
Adult
15-30 mg/kg/d PO; not to exceed 2 g/d
Alternatively, 1.5 g/d PO; increase to 2 g for body weight >75 kg, and decrease to 1 g for body weight <50 kg
Pediatric
Administer as in adults
None reported
Documented hypersensitivity; severe hepatic damage; acute gout
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Use only in combination with other effective antituberculous agents; inhibits renal excretion of urates; may result in hyperuricemia (usually asymptomatic); perform baseline serum uric acid determinations; discontinue drug if signs of hyperuricemia with acute gouty arthritis; perform baseline LFTs (closely monitor in liver disease); discontinue if signs of hepatocellular damage appear; caution in history of diabetes mellitus
Ethambutol (Myambutol)
Diffuses into actively growing mycobacterial cells, such as tubercle bacilli. Impairs cell metabolism by inhibiting synthesis of one or more metabolites, which, in turn, causes cell death. No cross-resistance demonstrated.
Mycobacterial resistance is frequent with previous therapy. Use in these patients in combination with second-line drugs that have not been previously administered.
Administer q24h until permanent bacteriological conversion and maximal clinical improvement is seen. Absorption is not significantly altered by food.
Adult
No previous antituberculous therapy: 15 mg/kg/d (7 mg/lb/d) PO
Previous antituberculous therapy: 25 mg/kg/d (11 mg/lb/d) PO
Absorption not significantly altered by administration with food
Pediatric
<12 years: Not recommended
>12 years: Administer as in adults
Aluminum salts may delay and reduce absorption (give several hours before or after EMB dose)
Documented hypersensitivity, optic neuritis (unless clinically indicated)
Pregnancy
B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals
Precautions
Reduce dose in impaired renal function; may have reversible visual adverse effects if promptly discontinued
Streptomycin sulfate
For treatment of susceptible mycobacterial infections.
Use in combination with other antituberculous drugs (eg, INH, EMB, rifampin). Total period of treatment for TB is a minimum of 1 y; however, indications for terminating streptomycin therapy may occur at any time.
Recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.
May be used in patients with severe liver dysfunction (transaminases >3- to 5-fold normal).
Adult
2 times/wk dosing: 15 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d
Pediatric
2 times/wk dosing: 20-40 mg/kg/d IM; not to exceed 1 g/d
3 times/wk dosing: 25-30 mg/kg/d IM; not to exceed 1.5 g/d
Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics
Documented hypersensitivity, non–dialysis-dependent renal insufficiency
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Narrow therapeutic index; not intended for long-term therapy; caution in renal failure not on dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission
Levofloxacin (Levaquin)
Second-line drug with low risk of liver toxicity. Useful in TB in combination with rifampin and other antituberculosis agents. Other quinolones also may be useful, especially newer quinolones.
Adult
500 mg/d PO
Pediatric
<18 years: Not recommended, although it has been used in MDR-TB when options are limited
>18 years: Administer as in adults
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase serum concentrations
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Documented hypersensitivity; viral infections of the eye, fungal diseases of the ocular structure, with steroid combinations after uncomplicated removal of a corneal foreign body
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
In prolonged therapy, periodically evaluate organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Cycloserine (Seromycin)
Inhibits cell-wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in M tuberculosis. Structural analogue of D-alanine, which antagonizes role of D-alanine in bacterial cell-wall synthesis, inhibiting their growth.
Adult
250-500 mg PO bid for the first 2 wk; not to exceed 1 g/d; administer pyridoxine at 200-300 mg/d to prevent neurotoxic effects
Pediatric
10-20 mg/kg/d PO; not to exceed 0.75-1 g/d
Incompatible with alcohol consumption because may increase possibility and risk of epileptic episodes; INH in combination with cycloserine may result in increased adverse CNS effects of cycloserine, such as dizziness
Documented hypersensitivity; severe anxiety or psychosis; epilepsy; depression; severe renal insufficiency; alcoholism; severe neurological impairments
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Discontinue drug or reduce dosage if allergic dermatitis or symptoms of CNS toxicity, such as convulsions, headache, tremor, depression, confusion, psychosis, somnolence, hyperreflexia, vertigo, paresis, or dysarthria, develop; risk of convulsions is increased in patients with chronic alcoholism; administration has been associated with vitamin B-12 and folic acid deficiency, megaloblastic anemia, and sideroblastic anemia; monitor blood levels weekly in reduced renal function, patients receiving more than 500 mg/d, and those with symptoms of toxicity
Ethionamide (Trecator-SC)
Bacteriostatic against M tuberculosis. Recommended when treatment with first-line drugs (INH, rifampin) has failed. Treats any form of active TB; however, should be used only with other effective antituberculous agents.
Adult
15-20 mg/kg or 0.5-1 g/d PO divided qid
Concomitant administration of 25 mg/d pyridoxine recommended
Pediatric
15-20 mg/kg/d PO divided tid/qid; not to exceed 1 g/d
Concomitant administration of 25 mg/d pyridoxine recommended
None reported
Documented hypersensitivity, severe hepatic damage
Pregnancy
X - Contraindicated; benefit does not outweigh risk
Precautions
Measure serum transaminase (AST, ALT) prior to therapy and q2-4wk thereafter; perform in vitro susceptibility tests of recent cultures of M tuberculosis from patient with ethionamide and usual first-line antituberculous drugs; management of diabetes mellitus may be more difficult, and hepatitis may occur more frequently
Capreomycin (Capastat sulfate)
Obtained from Streptomyces capreolus for coadministration with other antituberculous agents in pulmonary infections caused by capreomycin-susceptible strains of M tuberculosis.
For use only when first-line agents (eg, INH, rifampin) have been ineffective or cannot be used because of toxicity or presence of resistant tubercle bacilli. Important drug for MDR-TB.
Adult
1 g/d IM for 60-120 days, followed by 1 g IM 2-3 times/wk; not to exceed 20 mg/kg/d
Pediatric
15-20 mg/kg/d IM; not to exceed 1 g/d
Coadministration with aminoglycosides may increase risk of respiratory paralysis and renal dysfunction; with nondepolarizing neuromuscular blocking agents, has synergistic effects on myoneural function
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Assess vestibular auditory function prior to therapy and regularly while treating; monitor renal function throughout treatment (reduce dose in renal impairment); monitor serum potassium levels
Amikacin (Amikin)
Aminoglycoside antibiotic used for gram-negative bacterial coverage for infections resistant to gentamicin and tobramycin.
Irreversibly binds to 30S subunit of bacterial ribosomes, blocking recognition step in protein synthesis and causing misreading of genetic code.
Use patient's ideal body weight for dosage calculation.
Adult
15 mg/kg/d IV/IM divided bid; not to exceed 1.5 g/d regardless of high body weight
Pediatric
Administer as in adults
Coadministration with other aminoglycosides, penicillins, cephalosporins, and amphotericin B increases nephrotoxicity; enhances effects of neuromuscular blocking agents; causes respiratory depression; irreversible hearing loss may occur with coadministration of loop diuretics
Documented hypersensitivity
Pregnancy
D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus
Precautions
Not intended for long-term therapy; caution in patients with renal failure (not on dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission
Paraaminosalicylic acid (Paser)
Bacteriostatic agent useful against M tuberculosis. Inhibits the onset of bacterial resistance to streptomycin and INH. Administer aminosalicylate sodium with other antituberculous drugs.
PAS is often poorly tolerated because of diarrhea. Administer with applesauce to increase absorption.
Adult
150 mg/kg PO divided bid/tid; not to exceed 10-16 g/d
Pediatric
275-420 mg/kg/d PO tid/qid
Oral absorption of digoxin may be reduced, causing a reduction in serum levels when administered concurrently with PAS; an increase in digoxin dosing may be necessary; a deficiency in vitamin B-12 (oral) may be induced because of PAS interference of its GI absorption; parenteral vitamin B-12 supplementation may be required
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Caution in gastric ulcer and history of congestive heart failure; avoid situations in which excess sodium is potentially harmful
Rifabutin (Mycobutin)
Antibiotic derived from rifamycin S. Inhibits DNA-dependent RNA polymerase, preventing chain initiation in susceptible strains of Escherichia coli and Bacillus subtilis but not in mammalian cells. If GI upset, administer dose bid with food.
Useful in the treatment of rare TB cases with R resistance and RB susceptibility and of patients with HIV infection who are on protease inhibitors (eg, indinavir or nelfinavir).
Adult
300-600 mg/d PO; alternatively, 10-20 mg/kg/d PO, not to exceed 600 mg/d
If GI upset, administer dose bid with food
Patients taking indinavir: 150 mg PO with indinavir; often can be changed to 150-300 mg 2 d/wk after first 2 wk; patients on other protease inhibitors also may need dose adjustments
Pediatric
10-20 mg/kg/d PO; not to exceed 600 mg/d
If GI upset, administer bid with food
Steady-state zidovudine plasma levels may decrease after repeated rifabutin dosing but does not affect inhibition of HIV by zidovudine
Documented hypersensitivity
Pregnancy
C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus
Precautions
Do not administer to patients with active TB; no evidence rifabutin is effective in prophylaxis against M tuberculosis; may give INH and rifabutin concurrently in patients requiring prophylaxis against both M tuberculosis and Mycobacterium avium complex; perform hematologic studies periodically in patients receiving prophylaxis because of the association with neutropenia and, more rarely, thrombocytopenia
More on Miliary Tuberculosis |
| Overview: Miliary Tuberculosis |
| Differential Diagnoses & Workup: Miliary Tuberculosis |
 Treatment & Medication: Miliary Tuberculosis |
| Follow-up: Miliary Tuberculosis |
| References |
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References
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Further Reading
Keywords
miliary tuberculosis, miliary TB, TB bacilli, disseminated tuberculosis, TB, mycobacteremia, cryptogenic tuberculosis, Mycobacterium tuberculosis, M tuberculosis, mycobacteremia
