eMedicine Specialties > Emergency Medicine > Infectious Diseases
Tuberculosis: Treatment & Medication
Updated: Jan 26, 2009
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
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Treatment
Prehospital Care
- Prehospital providers should be equipped with respiratory masks meeting standards for prevention of TB transmission and should receive annual tuberculin skin testing.
- For high-risk cases, prehospital workers can assist in identifying household contacts who may also be infected or who may be at high risk of becoming infected. Prehospital workers should be aware that any case of active TB in a child indicates disease in one or more adults within the same household.
- A special regimen exists for patients with TB who are actively seizing or who have overdosed on antimycobacterial medication.
- In these patients, overdose with isoniazid (INH) should be suspected.
- Diazepam can be attempted to control seizure activity, but intravenous pyridoxine is the drug of choice, in a gram-for-INH-ingested-gram dose. (If the ingested dose is unknown, 5 g of pyridoxine can be used empirically.)
- For patients who are awake and alert, an oral dose of activated charcoal (1 g/kg) with sorbitol can be administered.
Emergency Department Care
Triage protocols
In the article by Moran et al, the need for universal triage protocols was addressed. Of patients with active TB with confirmed AFB’s, 51% of the patients were not isolated and had delayed treatment and infectious control.7 The presence of cough, chest radiographic results typical of TB, weight loss, fever, and night sweats were all statistically significant findings in those who were positive for active TB. Delays in recognition can facilitate the rise of nosocomial outbreaks of TB, especially MDR in health care workers; TB skin conversion rates among health care workers during these outbreaks ranged from 33-50%.
Implementation of an emergency department triage procedure for the detection and isolation with active pulmonary TB has been recently tested with a triage screening protocol known as the Rapid Isolation of Pulmonary Tuberculosis (RIPT) screen. It is a scoring system (0-24 points) utilizing risk factors and symptoms assigned to a point value for qualifications of isolation. A cumulative score of 4 or more (5 or more if chief complaint was asthma exacerbation) was considered positive screen findings and patients were immediately isolated and a chest radiograph was taken. Symptoms included hemoptysis, cough, fever, chills, night sweats, and weight loss more than 10 lb. Risk factors included HIV, homeless/living in a shelter, living in jail, newly PPD positive, male homosexual, foreign born, intravenous drug users, and use of chemotherapy/steroids.
Unfortunately, the RIPT screening instrument had a disappointing sensitivity of 63% and estimated specificity of 78%. This resulted in a poor capture of the high-risk patients for TB.
Screening patients at ED triage is an enormous task and at this time no universal standardized protocol exists for appropriate identification of suspected TB infection. However, this does not mitigate the need to recognize and isolate patients with a high degree of suspicion to facilitate shorter time elapsed before infection-control measures are implemented in the ED. This is critical for protection of the public and health care providers alike.
Recommendations
Isolate any patient with suspected TB infection in a private room (not cohorted, as in the past), ideally with negative pressure. Anyone entering should wear high-efficiency disposable masks sufficient to filter the TB bacillus. Continue isolation until sputum smears return negative results 3 consecutive times. Such sterilization usually requires 2-4 weeks of treatment and must be accompanied by clinical improvement.
- Initial 4-drug therapy is recommended in most areas. Intermittent treatment is as effective as daily treatment (approximately 2% relapses) with the advantage of increased compliance (see below).
- Six-month course, daily therapy - The compliance rate is 61%.
- Initial 2 months (all PO doses) - Isoniazid (INH) 300 mg qd (pediatric dose: 10-20 mg/kg/d, not to exceed 300 mg/d); rifampin (RIF) 600 mg qd (pediatric dose: 10 mg/kg/d, not to exceed 600 mg/d); pyrazinamide (PZA) 2 g qd (pediatric dose: 25 mg/kg/d, not to exceed 2 g/d); and ethambutol (ETB) 2 g qd (pediatric dose: 25 mg/kg/d, not to exceed 2 g/d)
- ETB may be dropped if TB culture drug sensitivities return favorable results.
- Final 4 months (if initial 2 months are successful by smear conversion and resolving symptoms) - INH 300 mg qd and RIF 600 mg qd or, alternatively, INH 900 mg and RIF 600 mg twice weekly
- Six-month course of directly observed intermittent therapy (DOTS: Denver protocol) - The compliance rate is 91%.
- Initial 2 weeks (all PO doses except for streptomycin, which is administered IM) - INH 300 mg qd, RIF 600 mg qd, PZA 2 g qd, and streptomycin 1 g qd (pediatric dose: 20 mg/kg/d, not to exceed 1000 mg/d)
- Next 6 weeks - Same drugs twice weekly
- Final 18 weeks - INH and RIF only, twice weekly
- Relapse rate - Comparable to daily 6-month protocol (1.6%)
- DOTS-Plus Strategy with considerations of the WHO guidelines have been studied. Results for treatment of patients with MDR-TB in Latvia have been encouraging; 66% of patients were cured or completed therapy, 7% died, and 14% did not respond to treatment.
- Six-month course, daily therapy - The compliance rate is 61%.
Special cases
Multi–drug-resistant tuberculosis
- Once MDR-TB is suspected due to relevant history or epidemiologic information and after sputum is cultured with anti-TB drug sensitivity, treatment is implemented. Treatment must be started empirically prior to culture results; once results are known modification of therapy is necessary according to susceptibilities.
- When initiating treatment, utilize at least 3-5 previously unused drugs in which there is in vitro susceptibility. The fluoroquinolone levofloxacin has been shown to be best suited long term and should be included in the regimen.
- The complexity of MDR-TB treatment lies in the futility of using isoniazid and rifampin. Isoniazid is the strongest antibactericidal action and significantly contributes to making patients rapidly noninfectious; rifampin has unique antibacterial properties against dormant bacilli that are no longer in the active phase of replication; rifampin alone had enabled the reduction of drug-susceptible TB treatment for 18-24 months to current 6-9 months.
- Two suggested regimens include (1) pyrazinamide 25-30 mg/kg daily plus ethambutol 15-25 mg/kg daily or (2) pyrazinamide 25-30 mg/kg daily plus a quinolone such as levofloxacin; both regimens are recommended for 12 months in patients who are immunosuppressed or for at least 6 months with other patients.
- Never add a new drug to a failing regimen.
- Administer at least 3, preferably 4-5 of the following medications according to drug susceptibilities: aminoglycosides (ie, streptomycin, amikacin, capreomycin, kanamycin); fluoroquinolone (ie, levofloxacin, ciprofloxacin, ofloxacin); thioamides such as ethionamide or prothionamide; pyrazinamide; ethambutol; cycloserine; terizodone; or para-aminosalicylic acid.
- Consider rifabutin substitution for rifampin (RIF), as approximately 15% of RIF-resistant strains are rifabutin sensitive.
- Do not use intermittent therapy.
- Surgery is recommended for patients with MDR-TB whose prognosis with medical treatment is poor. Surgery can be performed with a low mortality rate (<3%) with prolonged periods of a chemotherapeutic regimen for more than 1 year after surgery.
- All patients should be closely observed for 2 years with a low threshold for referral to TB centers.
- Clusters of MDR-TB with 7-drug resistance have been reported and have a high infectivity rate.
- The health care worker PPD conversion rate is 18-50% with exposure to MDR-TB.
- Success of treatment in MDR-TB include factors such as a lower prior exposure to anti-TB drugs, a higher number of anti-TB drugs to which the infection is still susceptible, and a shorter time since the first TB diagnosis (indicating a less advanced disease) indicate a great chance of successful treatment.
- Successful treatment of MDR-TB includes specialized expertise, diagnostic techniques, drugs, and patient compliance/adherence to regimen.
Patients who are HIV positive
Extend the treatment protocol to a minimum of 9 months (final stage, 7 months) with at least 6 months' culture-negative sputum.
Patients who are pregnant
A 9-month daily course of INH, RIF, and ETB is recommended in the doses above.
- Breastfeeding is permitted.
- PZA is contraindicated due to inadequate teratogenicity data.
- Streptomycin is discouraged unless other drugs are contraindicated (16% fetal ototoxicity).
Patients who have meningitis
Dexamethasone added to routine 4-drug therapy reduces complications.
Consultations
Because of changing recommendations, particularly with regard to the treatment of drug-resistant TB, expert consultation for TB management is available from several national centers.
- For information on current national policies and recommendations, call the CDC Division of Tuberculosis Elimination at (404) 639-8140. The CDC Voice and Fax Information System is also available at (888) 232-3228.
- For expert consultation on the management of drug-resistant TB, call one of the following national Model TB Centers:
- San Francisco Model TB Center - (415) 502-4600
- New York City Model TB Center - (212) 939-8254
Medication
Treatment of tuberculosis has 3 basic therapeutic principles. First, any regimen must use multiple drugs to which M tuberculosis is susceptible. Second, the therapy must be taken regularly. Third, the therapy must continue for a period sufficient to resolve the illness. New cases are initially treated with 4 drugs: isoniazid (INH), rifampin, pyrazinamide, and either ethambutol or streptomycin for 2 months, then with a continuation phase of 4 months with INH and rifampin. Re-treatment cases initially receive 5 drug treatments with INH, rifampin, streptomycin (only for 2 mo), ethambutol and pyrazinamide for 3 months, and INH, rifampin and ethambutol for 5 months.In the United States, anti-TB therapy is available to all patients at no cost through the Department of Health (see Emergency Department Care).
Antitubercular agents
Patients thought to have pulmonary TB whose sputum smear returns positive for acid-fast bacillus can be presumptively diagnosed and treated with anti-TB therapy. TB therapy also may be appropriate in patients with a negative sputum smear who have clinical and radiographic findings consistent with pulmonary TB. Immediately treat severely ill patients with presumed TB. The role of linezolid, clarithromycin, beta-lactams, clofazimine, phenothiazines, and nitroimidazopyrans have been suggested, but studies are limited. MDR-TB such nitroimidazopyran nucleic PA-284 compound, LL3858 LL3522 pyrroles, immunotherapy, potential vaccines, cytokine therapy, and R207910 has shown much promise as well.
Ofloxacin (Floxin)
Broad-spectrum fluoroquinolone that inhibits DNA gyrase. Good gram-positive coverage and excellent gram-negative coverage but poor anaerobic coverage.
Adult
400 mg PO bid
Pediatric
Not established
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; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
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
Isoniazid (Laniazid, Nydrazid)
Best combination of effectiveness, low cost, and minor adverse effects. First-line drug unless known resistance or another contraindication exists. Therapeutic regimens of <6 mo demonstrate unacceptably high relapse rates. Coadministration of pyridoxine is recommended if peripheral neuropathies secondary to INH therapy develop. Prophylactic doses of 6-50 mg of pyridoxine daily are recommended.
Adult
5 mg/kg PO qd (usually 300 mg/d); not to exceed 300 mg/d
Pediatric
10-20 mg/kg PO qd; not to exceed 300 mg/d
Higher incidence of INH-related hepatitis can occur with daily alcohol ingestion; aluminum salts may decrease INH 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 CNS adverse effects (eg, dizziness); acute behavioral and coordination changes may occur with coadministration of disulfiram; coadministration with RIF after halothane anesthesia may result in hepatotoxicity and hepatic encephalopathy; may inhibit hepatic microsomal enzymes and increase toxicity of hydantoin.
Documented hypersensitivity; previous INH-associated hepatic injury or 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 INH therapy are recommended even when visual symptoms do not occur
Rifampin (Rifadin, Rifadin IV, Rimactane)
For use in combination with at least 1 other anti-TB drug; inhibits DNA-dependent bacterial polymerase but not mammalian RNA polymerase. Cross-resistance may occur. Treat for 6-9 mo or until 6 mo have elapsed from conversion to sputum culture negativity.
Adult
600 mg PO/IV qd
Pediatric
10-20 mg/kg PO/IV; 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 INH may result in higher rate of hepatotoxicity than with either agent alone (discontinue one or both agents if alterations in LFTs occur).
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
Obtain CBCs 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
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 patients. Treat drug-resistant patients with individualized regimens.
Adult
15-30 mg/kg PO qd; not to exceed 2 g/d ; in MDR-TB: 20-30 mg/kg (1,200-1,600 mg)
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 anti-TB 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 manifest; perform baseline LFTs (closely monitor in liver disease); discontinue if signs of hepatocellular damage appear; caution in history of diabetes mellitus, hyperuricemia, arthralgias, and GI intolerance
Ethambutol (Myambutol)
Diffuses into actively growing Mycobacterium cells such as tubercle bacilli. Inhibition in the synthesis of one or more metabolites impairs cell metabolism, which, in turn, inhibits bacterial multiplication and causes cell death. No cross-resistance with other agents has been demonstrated. Mycobacterial resistance to drugs used in initial therapy is frequent in patients who have received previous therapy. Useful in treatment of these groups of patients when administered with at least one of the second-line drugs that have not previously been administered to the patient and to which bacterial susceptibility has been shown. Administer this medication once every 24 h only, and continue therapy until bacteriological conversion has become permanent and maximal clinical improvement has occurred. Absorption is not significantly altered by administration with food.
Adult
No previous anti-TB therapy: 15 mg/kg (7 mg/lb) PO qd
Previous anti-TB therapy: 25 mg/kg (11 mg/lb) PO qd MDR-TB: 15-20 mg/kg (1,000-1,200 mg)
Pediatric
<13 years: Not recommended
>13 years: Administer as in adults
Aluminum salts may delay and reduce absorption (administer several hours before or after ETB 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 anti-TB drugs (eg, INH, ETB, RIF). Bactericidal on only replicating mycobacteria therefore best used in only induction phase. Total period of treatment of 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. Amikacin and kanamycin similar profile.
Adult
1 g IM qd
MDR-TB: 15 mg/kg (750-1,000 mg) (Same for kanamycin and amikacin dosing)
Pediatric
20-40 mg/kg/d IM; not to exceed 1 g/d
Nephrotoxicity may be increased with aminoglycosides, cephalosporins, penicillins, amphotericin B, and loop diuretics.
Documented hypersensitivity; non–dialysis-dependent renal insufficiency
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
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; ototoxicity (vertigo/deafness), nephrotoxicity, hemolytic anemia, aplastic anemia, agranulocytosis, thrombocytopenia, and lupoid reactions; amikacin known to have less vestibulotoxic and nephrotoxic effects: may be more beneficial if long term use
Levofloxacin (Levaquin)
Inhibits growth of susceptible organisms by inhibiting DNA gyrase and promoting breakage of DNA strands intracellularly. Similar profiles with ciprofloxacin, ofloxacin, sparfloxacin, gatifloxacin, and moxifloxacin.
Adult
750 mg PO q24h for 7-14 d; MDR-TB: 200-1000 mg; gatifloxacin 400 mg qd (bactericidal), moxifloxacin 400 mg qd (bactericidal), ciprofloxacin 1000 qd (weakly bactericidal); ofloxacin 800 mg qd (weakly bactericidal)
Pediatric
Not established
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; levofloxacin reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
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
Ethionamide (Trecator)
Bacteriocidal against M tuberculosis. Type of thiomide. Recommended when treatment with first-line drugs (INH, RIF) has failed. Treats any form of active TB. Use only with other effective anti-TB agents. Profile similar as prothionamide.
Adult
0.5-1 g/d PO divided qid; concomitant administration of pyridoxine recommended; MDR-TB: 10-20 mg/kg (500-750 mg); same dosing for prothionamide
Pediatric
15-20 mg/kg/d PO divided tid/qid; not to exceed 1 g/d; concomitant administration of pyridoxine recommended
None reported
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) levels 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 anti-TB drugs; management of diabetes mellitus may be more difficult, and hepatitis may occur more frequently; epigastric discomfort, anorexia, nausea, metallic taste, vomiting, excessive salivation, psychosis (ie, hallucinations and depression), hypoglycemia, hypothyroidism, gynecomastia, impotence, peripheral neuropathy, headache
Capreomycin (Capastat)
Obtained from Streptomyces capreolus for coadministration with other anti-TB agents in pulmonary infections caused by capreomycin-susceptible strains of M tuberculosis. For use only when first-line agents (eg, INH, RIF) have been ineffective or cannot be used because of toxicity or presence of resistant tubercle bacilli.
Adult
1 g IM qd for 60-120 d; followed by 1 g IM 2-3 times weekly; not to exceed 20 mg/kg/d; MDR-TB: 15 mg/kg (750-1,000 mg)
Pediatric
15 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
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; hypokalemia, hypocalcemia, hypomagnesemia, cutaneous reactions
Clofazimine (Lamprene)
Inhibits mycobacterial growth, binds preferentially to mycobacterial DNA. Has antimicrobial properties, but mechanism of action is unknown. Always use with other anti-TB agents.
Adult
100 mg/d PO
Pediatric
1 mg/kg/d PO
Dapsone may inhibit anti-inflammatory activity
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
Severe abdominal symptoms may require exploratory laparotomies; caution in patients with GI problems (eg, abdominal pain, diarrhea); skin discoloration due to drug may result in depression or suicide; apply oil to skin for dryness and ichthyosis
Cycloserine (Seromycin)
Inhibits cell wall synthesis in susceptible strains of gram-positive and gram-negative bacteria and in M tuberculosis. Bacteriostatic structural analogue of D-alanine, which antagonizes role of D-alanine in bacterial cell wall synthesis, thus inhibiting their growth.
Adult
500 mg to 1 g PO qd in divided doses monitored by blood levels
Alternatively, 250-500 mg PO bid for first 2 wk; not to exceed 1 g/d
MDR-TB: 15-20 mg/kg (500-750 mg)
Pyridoxine administered at 200-300 mg/d may 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; isoniazid in combination with cycloserine may result in increased cycloserine CNS side effects such as dizziness
Documented hypersensitivity; severe anxiety or psychosis, epilepsy, depression; severe renal insufficiency; alcoholism; patients with severe neurological impairments should not receive the drug
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 persons 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; dizziness, slurred speech, convulsions
Dapsone (Avlosulfon)
Bactericidal as well as bacteriostatic against Mycobacterium strains. Mechanism of action is similar to that of sulfonamides, in which competitive antagonists of PABA prevent the formation of folic acid, causing bacterial growth inhibition. Use in the treatment of TB is largely experimental.
Adult
50-300 mg/d PO
Pediatric
1-2 mg/kg/d PO; not to exceed 100 mg/d
May inhibit anti-inflammatory effects of clofazimine; hematologic reactions may increase with folic acid antagonists, eg, pyrimethamine (monitor for agranulocytosis during the second and third months of therapy); probenecid increases toxicity; trimethoprim with dapsone may increase toxicity of both drugs; due to increased renal clearance, dapsone levels may significantly decrease when administered concurrently with RIF
Documented hypersensitivity; known G-6-PD deficiency
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 weekly blood counts (first month); then perform WBC counts monthly (6 mo); then semiannually; discontinue if significant reduction in platelets, leukocytes, or hematopoiesis is seen; caution in methemoglobin reductase deficiency, G-6-PD deficiency (patients receiving >200 mg/d), or hemoglobin M because of high risk for hemolysis and Heinz body formation; caution in patients exposed to other agents or conditions (eg, infection, diabetic ketosis) capable of producing hemolysis; peripheral neuropathy can occur (rare); phototoxicity may occur when exposed to UV light
Gatifloxacin (Tequin)
Quinolone that has antimicrobial activity based on ability to inhibit bacterial DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Differences in chemical structure between quinolones have resulted in altered levels of activity against different bacteria. Altered chemistry in quinolones result in toxicity differences.
Adult
400 mg PO/IV qd
Pediatric
<18 years: Not recommended
>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; may reduce therapeutic effects of phenytoin; probenecid may increase serum concentrations of quinolones
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Documented hypersensitivity; diabetes mellitus
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
Quinolones increase risk of pseudomembranous colitis caused by Clostridium difficile; may cause severe photosensitivity reactions in patients exposed to sunlight or UV light; have been associated with a variety of CNS manifestations such as hallucinations and seizures; factors that increase risk of adverse effects should be noted when considering use of any quinolone; caution in renal insufficiency (adjust dose)
Moxifloxacin (Avelox)
Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription.
Adult
400 mg PO/IV qd
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
Antacids, electrolyte supplements reduce absorption; loop diuretics, probenecid, cimetidine increase serum levels; NSAIDs enhance CNS stimulating effect
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT); ferrous sulfate decreases bioavailability (administer moxifloxacin 4 h prior or 8 h following ferrous sulfate); coadministration with drugs that prolong QTc interval (quinidine, procainamide, amiodarone, sotalol, erythromycin, tricyclic antidepressants) increase risk of life-threatening arrhythmia
Documented hypersensitivity; known Q-T prolongation, concurrent administration of drugs that cause Q-T prolongation
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); superinfections may occur with prolonged or repeated antibiotic therapy; fluoroquinolones have induced seizures in CNS disorders and caused tendinitis or tendon rupture
Ciprofloxacin (Cipro)
Fluoroquinolone that inhibits bacterial DNA synthesis and, consequently, growth, by inhibiting DNA gyrase and topoisomerases, which are required for replication, transcription, and translation of genetic material. Quinolones have broad activity against gram-positive and gram-negative aerobic organisms. Has no activity against anaerobes. Continue treatment for at least 2 d (7-14 d typical) after signs and symptoms have disappeared. For treatment of tuberculosis in combination with rifampin and other antituberculosis agents.
Adult
750 mg PO bid
Pediatric
<18 years: Not recommended
>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; ciprofloxacin reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations
May increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
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
Dosage adjustments (adult adjustments)
CrCl (mL/min) <10: 50% of PO or IV dose q12h
HD: 0.25-0.5 g PO or 0.2-0.4 g IV q12h
During peritoneal dialysis: 0.25-0.5 g PO or 0.2-0.4 g IV q8h
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
Not drug of first choice in pediatrics because of increased incidence of adverse events compared to controls, including arthropathy; no data exist for dose for pediatric patients with renal impairment (ie, CrCl <50 mL/min)
Para-aminosalicylate sodium
Bacteriostatic agent useful against Mycobacterium tuberculosis. Inhibits the onset of bacterial resistance to streptomycin and isoniazid.
Administer aminosalicylate sodium with other antituberculous drugs.
Adult
14-16 g/d PO divided bid/tid; MDR-TB: 150 mg/kg (10-12 g)
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 due to 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
More on Tuberculosis |
| Overview: Tuberculosis |
| Differential Diagnoses & Workup: Tuberculosis |
 Treatment & Medication: Tuberculosis |
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| Multimedia: Tuberculosis |
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References
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Further Reading
Keywords
tuberculosis, TB, lung disease, pulmonary disease, pulmonary infection, treatment of TB, Mycobacterium tuberculosis, M tuberculosis, mycobacterial infection, Pott's disease, Pott disease, scrofula, miliary disease, extrapulmonary TB, multi–drug-resistant tuberculosis, MDR-TB, extensively drug resistant tuberculosis, XDR-TB
