eMedicine Specialties > Infectious Diseases > Mycobacterial Infections

Tuberculosis: Treatment & Medication

Author: Thomas Herchline, MD, Professor of Medicine, Wright State University Boonshoft School of Medicine; Medical Director, Public Health, Dayton and Montgomery County, Ohio
Coauthor(s): Judith K Amorosa, MD, FACR, Clinical Professor and Program Director, Department of Radiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Consulting Staff, Department of Radiology, Robert Wood Johnson University Hospital
Contributor Information and Disclosures

Updated: Nov 11, 2009

Treatment

Medical Care

  • For initial empiric treatment of tuberculosis (TB), start patients on a 4-drug regimen: isoniazid, rifampin, pyrazinamide, and either ethambutol or streptomycin. Once the TB isolate is known to be fully susceptible, ethambutol (or streptomycin if used as a fourth drug) can be discontinued.
    • After 2 months of therapy (for a fully susceptible isolate), pyrazinamide can be stopped. Isoniazid plus rifampin are continued as daily or intermittent therapy for 4 more months.
    • If isolated isoniazid resistance is documented, discontinue isoniazid and continue treatment with rifampin, pyrazinamide, and ethambutol for the entire 6 months.
    • Therapy must be extended if the patient has cavitary disease or remains culture-positive after 2 months of treatment.
  • Directly observed therapy (DOT) is recommended for all patients. Patients on the above regimens as DOT can be switched to 2- to 3-times per week dosing after an initial 2 weeks of daily dosing. Patients on twice-weekly dosing must not miss any doses. Prescribe daily therapy for patients on self-administered medication.
  • The diagnosis of MDR-TB is established with an isolate that is resistant to both isoniazid and rifampin. Resistance may be initial (no known history of prior treatment) or secondary (acquired during therapy or because of previous inadequate therapy).
  • Risk factors for initial resistance include exposure to a patient who has MDR-TB or being from a country or region with a high prevalence of resistance. Symptoms and radiographic findings do not differentiate MDR-TB from fully susceptible TB. Suspect MDR-TB if the patient is on DOT with the 4 first-line drugs (no diarrhea) and symptoms do not improve within 1-2 weeks.
  • Continue treatment for MDR-TB for 18-24 months after sputum culture conversion. The drugs should be prescribed daily (no intermittent therapy), and the patient should always be on DOT. Weekend DOT may not be possible; therefore, giving self-administered oral drugs on Saturdays and Sundays may be reasonable. Consult an expert on MDR-TB. Costs are many times higher for treatment of MDR-TB. Treatment should include an injectable drug together with at least 3 more drugs to which the isolate is susceptible.
  • In a phase 2, randomized, controlled trial, Diacon et al studied patients with newly diagnosed multidrug-resistant pulmonary TB. Forty-seven patients were assigned either TMC207 (400 mg PO qd for 2 wk, then 200 mg tid for 6 wk) or placebo in combination with a standard 5-drug, second-line antituberculosis regimen. TMC207 added to standard therapy for MDR-TB reduced the time to conversion to a negative sputum culture compared with placebo (P = 0.003) and increased the proportion of patients with conversion of sputum culture (48% vs 9%). These data provide important results to continue investigation of TMC207 in a larger population for multidrug-resistant pulmonary TB.15
  • The diagnosis of extended drug-resistant TB (XDR-TB) is established with an isolate that is resistant to isoniazid, rifampin, at least one of the quinolones, and at least one injectable drug. Treatment options for XDR-TB are very limited, and XDR-TB carries a very high mortality rate.

Surgical Care

  • Surgical resection of an infected lung may be considered to reduce the bacillary burden in patients with MDR-TB. Procedures include segmentectomy (rarely used), lobectomy, and pneumonectomy. Pleurectomies for thick pleural peel are rarely indicated. However, intraoperative infection of uninvolved lung tissue has been observed.
  • Complications include the usual perioperative complications, recurrent disease, and bronchopleural fistulas.

Consultations

  • Infectious disease specialist
  • Pulmonologist
  • General or thoracic surgeon

Activity

Smoking has been shown to be a risk factor for TB; smokers who develop TB should be encouraged to stop smoking to decrease the risk of relapse.16

Medication

The goals of pharmacotherapy are to reduce morbidity and to prevent complications.

Antimycobacterials

The goals of tuberculosis (TB) treatment are to shorten the clinical course, to prevent complications, to prevent the development of latency and/or subsequent recurrences, and to decrease the likelihood of TB transmission. In patients with latent TB, the goal of therapy is to prevent progression of disease.


Isoniazid (Laniazid)

DOC for preventive therapy and primary drug in combination therapy for active TB. In patients receiving treatment for active TB, pyridoxine 25-50 mg PO qd should be coadministered to prevent peripheral neuropathy.

Adult

300 mg PO qd

Pediatric

10 mg/kg/d PO qd; not to exceed 300 mg/d

Higher incidence of isoniazid-related hepatitis can occur with daily alcohol ingestion; aluminum salts may decrease isoniazid serum levels (administer 1-2 h before taking aluminum salts); may increase effects of anticoagulants with coadministration; may inhibit metabolic clearance of benzodiazepines
Carbamazepine toxicity or isoniazid 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

Documented hypersensitivity; previous isoniazid-associated hepatic injury; other severe adverse reactions

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

Monitor patients with active chronic liver disease or severe renal dysfunction; periodic ophthalmologic examinations during isoniazid therapy are recommended even when visual symptoms do not occur


Rifampin (Rifadin, Rimactane)

For use in combination with at least one other antituberculous drug. Inhibits DNA-dependent bacterial but not mammalian RNA polymerase. Cross-resistance may occur.
Treat for 6 mo for most susceptible cases; 9 mo if sputum culture result is still positive after 2 mo of treatment.

Adult

600 mg PO qd

Pediatric

10-20 mg/kg/d PO qd; not to exceed 600 mg/d

Induces microsomal enzymes, which may decrease effects of acetaminophen, PO anticoagulants, barbiturates, benzodiazepines, beta-blockers, chloramphenicol, PO 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 isoniazid may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur)

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Obtain CBCs and baseline clinical chemistries before 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


Pyrazinamide (PZA)

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 TB. Treat drug-resistant TB with individualized regimens.

Adult

<50 kg: 1.5 g PO qd
50-75 kg: 2 g PO qd
>75 kg: 2.5 g PO qd

Pediatric

15-30 mg/kg/d PO qd; not to exceed 2 g/d

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 occur; perform baseline LFTs (closely monitor in liver disease); discontinue pyrazinamide if signs of hepatocellular damage appear; caution in history of diabetes mellitus


Ethambutol (Myambutol)

Diffuses into actively growing mycobacterial cells (eg, 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 are observed. Absorption is not significantly altered by food.

Adult

15-25 mg/kg PO qd

Pediatric

Administer as in adults

Aluminum salts may delay and reduce absorption (administered several hours before or after ethambutol 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 adverse visual effects if promptly discontinued


Streptomycin sulfate

For treatment of susceptible mycobacterial infections. Use in combination with other antituberculous drugs (eg, isoniazid, ethambutol, rifampin). Total period of treatment for TB is a minimum of 6 mo; however, streptomycin therapy is not commonly used for the duration of therapy. Recommended when less potentially hazardous therapeutic agents are ineffective or contraindicated.

Adult

15 mg/kg IM qd; can be administered 3-5 d/wk

Pediatric

20-30 mg/kg IM qd

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, patient not taking dialysis; caution with myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission


Levofloxacin (Levaquin)

Second-line drug. Useful in the treatment of TB in combination with rifampin and other antituberculous agents. Useful in treating most cases of MDR-TB.

Adult

500-1000 mg PO qd

Pediatric

<18 years: Not recommended unless no alternates available

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)

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, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy


Rifapentine (Priftin)

Used in once-weekly regimens along with isoniazid. Should not be used in individuals with HIV or with positive cultures after 2 mo of treatment.

Adult

600 mg PO qwk during the continuation phase of treatment for TB; given in combination with isoniazid for susceptible organism

Pediatric

Not established

Induces cytochrome P 4503 A 4 and P 4502 C 8/9, thereby decreasing levels of other drugs that are metabolized by these enzymes; may decrease plasma concentration of calcium channel blockers (verapamil, nifedipine, diltiazem), methadone, oral anticoagulants, oral contraceptives, benzodiazepines, acetaminophen, dapsone, clofibrate, doxycycline, levothyroxine, nortriptyline, tacrolimus, zidovudine, protease inhibitors, hydantoins, sulfa drugs, or enalapril; toxicity may increase when taken concurrently with halothane or isoniazid

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

Adverse effects include serious hepatic events, including hepatitis and liver failure; Clostridium difficile -associated colitis; hyperbilirubinemia; urticaria; thrombocytopenia; hyperkalemia; fatigue; gout; may cause red-orange discoloration of body fluids (eg, tears, urine, sweat, CSF)


Para-aminosalicylic acid (Sodium PAS)

Second-line drug. Bacteriostatic agent useful against M tuberculosis. Inhibits the onset of bacterial resistance to streptomycin and isoniazid. Administer aminosalicylate sodium with other antituberculous drugs.

Adult

4-6 g PO bid

Pediatric

75 mg/kg PO bid

PO absorption of digoxin may be reduced, causing a reduction in serum levels when administered concurrently with PAS; increase in digoxin dosing may be necessary; a deficiency in vitamin B-12 (PO) may be induced because of PAS interference of its GI absorption; parenteral vitamin B-12 supplementation may be required

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in gastric ulcer and history of congestive heart failure; avoid situations in which excess sodium is potentially harmful


Ethionamide (Trecator-SC)

Second-line drug. Bacteriostatic against M tuberculosis. Recommended if treatment with first-line drugs (isoniazid, rifampin) is unsuccessful. Treats any form of active TB. However, should only be used with other effective antituberculous agents.

Adult

250-500 mg PO bid

Pediatric

15-20 mg/kg PO bid

Hepatotoxicity increases when used concurrently with rifampin

Documented hypersensitivity; severe hepatic damage

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

Make determinations of 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


Amikacin (Amikin)

Second-line drug. Irreversibly binds to 30S subunit of bacterial ribosomes; blocks recognition step in protein synthesis; causes growth inhibition. Use patient's IBW for dosage calculation.

Adult

15 mg/kg IM qd; can administer 3-5 d/wk

Pediatric

15-30 mg/kg IM qd

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

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 (patient not taking dialysis), hypocalcemia, myasthenia gravis, and conditions that depress neuromuscular transmission


Cycloserine (Seromycin)

Second-line drug. 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 growth.

Adult

250-500 mg PO bid

Pediatric

10-20 mg/kg PO bid

Incompatible with alcohol consumption because may increase possibility and risk of epileptic episodes; isoniazid in combination with cycloserine may result in increased adverse cycloserine CNS effects (eg, dizziness)

Documented hypersensitivity; severe anxiety or psychosis; epilepsy; depression; severe renal insufficiency; alcoholism; severe neurologic impairments

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Discontinue drug or reduce dosage if allergic dermatitis or symptoms of CNS toxicity (eg, convulsions, headache, tremor, depression, confusion, psychosis, somnolence, hyperreflexia, vertigo, paresis, or dysarthria) develop; risk of convulsions is increased in long-term 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 >500 mg/d, and patients with symptoms of toxicity


Capreomycin (Capastat)

A second-line drug. 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, isoniazid, rifampin) have been ineffective or cannot be used because of toxicity or presence of resistant tubercle bacilli.

Adult

15 mg/kg IM qd; also administered as IV infusion

Pediatric

15-30 mg/kg IM qd

Coadministration with aminoglycosides may increase risk of respiratory paralysis and renal dysfunction; with nondepolarizing neuromuscular-blocking agents, has synergistic effects on myoneural function

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

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


Rifabutin (Mycobutin)

Ansamycin antibiotic derived from rifamycin S. Inhibits DNA-dependent RNA polymerase, preventing chain initiation. Used in treatment for TB in individuals on specific HIV medications, when rifampin is contraindicated (most protease inhibitors).

Adult

300 mg PO qd; as part of an intermittent regimen, 300 mg PO 3 times/wk

Pediatric

Not established; suggested dose is 5 mg/kg/d PO

Decreases plasma concentration of methadone, verapamil, cyclosporine, digoxin, corticosteroids, oral anticoagulants, barbiturates, theophylline, quinidine, halothane, protease inhibitors, non-nucleoside reverse transcriptase inhibitors, oral contraceptives, ketoconazole, and chloramphenicol; toxicity of rifabutin increases when administered concurrently with indinavir, ketoconazole, itraconazole, ritonavir, erythromycin, or protease inhibitors

Documented hypersensitivity; WBC count <1000/μL or platelet count <50,000/μL

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

Perform hematologic studies periodically due to association with neutropenia, and more rarely thrombocytopenia

More on Tuberculosis

Overview: Tuberculosis
Differential Diagnoses & Workup: Tuberculosis
Treatment & Medication: Tuberculosis
Follow-up: Tuberculosis
Multimedia: Tuberculosis
References

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Further Reading

Contributor Information and Disclosures

Author

Thomas Herchline, MD, Professor of Medicine, Wright State University Boonshoft School of Medicine; Medical Director, Public Health, Dayton and Montgomery County, Ohio
Thomas Herchline, MD is a member of the following medical societies: American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Coauthor(s)

Judith K Amorosa, MD, FACR, Clinical Professor and Program Director, Department of Radiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School; Consulting Staff, Department of Radiology, Robert Wood Johnson University Hospital
Judith K Amorosa, MD, FACR is a member of the following medical societies: American College of Radiology, American Roentgen Ray Society, Association of University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Nothing to disclose.

Medical Editor

John M Leedom, MD, Professor of Medicine, Keck School of Medicine, University of Southern California; Chief, Division of Infectious Diseases, Department of Internal Medicine, Los Angeles County, University of Southern California Medical Center
John M Leedom, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, American Society for Microbiology, Infectious Diseases Society of America, International AIDS Society, and Phi Beta Kappa
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Aaron Glatt, MD, Professor of Clinical Medicine, New York Medical College; President and CEO, Former Chief Medical Officer, Departments of Medicine and Infectious Diseases, New Island Hospital
Aaron Glatt, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physician Executives, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Medical Association, American Society for Microbiology, American Thoracic Society, American Venereal Disease Association, Infectious Diseases Society of America, International AIDS Society, and Society for Healthcare Epidemiology of America
Disclosure: Nothing to disclose.

CME Editor

Eleftherios Mylonakis, MD, Clinical and Research Fellow, Department of Internal Medicine, Division of Infectious Diseases, Massachusetts General Hospital
Eleftherios Mylonakis, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American Society for Microbiology, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

Chief Editor

Burke A Cunha, MD, Professor of Medicine, State University of New York School of Medicine at Stony Brook; Chief, Infectious Disease Division, Winthrop-University Hospital
Burke A Cunha, MD is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, and Infectious Diseases Society of America
Disclosure: Nothing to disclose.

 
 
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