BackgroundTuberculosis (TB) is an infection caused by organisms in the family Mycobacteria. These organisms grow slowly and can be identified only with special staining techniques, a trait that led to the name "acid-fast bacteria." Organisms in the Mycobacterium tuberculosis (MTB) group cause human disease, usually a chronic pneumonia. The destruction of MTB may produce holes or cavities in the lung containing huge numbers of organisms. MTB can also cause disease in other individual organs (eg, lymph nodes, meninges, bone, pericardium, peritoneum, intestines, urogenital tract) and can disseminate to multiple organs, often including the lungs, blood, liver, and spleen. TB is almost always transmitted by persons with active pulmonary TB who release large numbers of organisms in their sputum. The organisms remain suspended in the air for hours or days, making TB one of the most easily transmitted respiratory pathogens. Most immunologically healthy persons who are infected with MTB do not develop active TB but remain infected with inactive organisms (latent TB infection); only about 10% of infected persons develop active disease during their lifetimes. Persons with HIV infection have much higher rates of active TB and develop active disease at a rate approximating 10% per year. Before the development of effective treatment, half of all persons with TB disease died within about 5 years; others recovered but were prone to relapse. Appropriate application of modern chemotherapy to drug-susceptible MTB disease cured at least 95% of persons in the pre-HIV era. HIV and TB cause more deaths than any other infectious diseases worldwide, each claiming millions of lives annually. A biologic synergy exists between these infections: HIV-induced immunosuppression increases susceptibility to TB infection, and active TB infection enhances HIV replication through immunologic stimulation. The populations infected by these 2 pathogens overlap in many respects, creating epidemiologic synergy. Poverty, crowded living conditions, and inadequate efforts to reduce transmission combine to enhance the transmission of both organisms. In the United States, most cases of TB occur among immigrants, and TB is a relatively infrequent AIDS-defining illness. Nevertheless, TB remains important to HIV clinicians in the United States because it is highly infectious yet curable with proper treatment and because improper treatment leads to drug resistance both in the original patient and in those to whom that patient transmits. Although other conditions (eg, malnutrition, diabetes, end-stage renal disease, pulmonary silicosis, iatrogenic immunosuppression) increase the risk of TB disease, HIV is by far the most important risk factor. Classic pulmonary TB, with upper-lobe infiltrates and cavitary lesions, may occur in HIV-infected persons with relatively intact immunity. As the CD4 cell count decreases, TB is more likely to manifest atypically in the chest (without cavitary disease, or with lower-lobe disease, adenopathy, pleural effusions, or interstitial or miliary infiltrates), as extrapulmonary disease (particularly in lymph nodes, as meningitis, and as disseminated infection), or both. Bone, joint, and urogenital sites of TB are less commonly associated with HIV-induced immunosuppression. Symptoms and signs of TB in HIV-infected person therefore can vary widely. Improper or erratic treatment may cause resistance to TB medications. MTB resistance to a single drug may complicate treatment, but usually does not prevent successful treatment. Resistance to several drugs (polydrug resistance) requires a longer course of therapy using medications that are less potent and cause more adverse effects, and markedly reduces the chance of cure. Resistance to both isoniazid and rifampin is called multidrug resistance (MDR) and makes treatment especially difficult. It is extremely important to try to avoid the development of drug resistance, especially MDR. Treatment of drug-resistant TB should be managed by experts or in consultation with experts. S: SubjectivePersons with TB generally describe an illness lasting several weeks to months, associated with systemic features such as high fever, night sweats, loss of appetite, and weight loss. These symptoms may be nonspecific, but should raise the possibility of TB. - Pulmonary TB causes a chronic productive cough, sometimes with hemoptysis; shortness of breath occurs late in the disease.
- TB adenitis causes enlargement of the lymph nodes (usually asymmetric involvement in 1 region) which may suppurate and drain but usually are not painful, hot, or erythematous.
- TB meningitis causes headache, gradual change in mental status, and sometimes cranial nerve abnormalities such as double vision or decreased hearing.
- Disseminated TB may occur with only systemic manifestations such as fever, sweats, and weight loss, with no localizing features.
Risks for TB include known previous contact with an active case, previous positive result of a tuberculin skin test (TST, also known as a purified protein derivative test [PPD]), exposure in congregate settings (such as homeless shelters and prisons, but also health care facilities), or travel or residence in countries with high rates of endemic TB. In the United States, persons with active or past substance use disorders and persons of color are more likely than others to have had TB exposure. O: Objective- Measure vital signs, including oxygen saturation.
- Measure weight; compare with previous values.
- Perform thorough physical examination with particular attention to the lungs, heart, abdomen, lymph nodes, and neurologic system.
Systemic signs of chronic disease and inflammation are common, including fever, night sweats (which may occur without awareness of the high fever that precedes them), and weight loss. In patients with pulmonary TB, the breath sounds may be normal or focally abnormal; tachypnea and hypoxia occur only with extensive lung damage. Extrapulmonary TB may present with focal adenopathy without local signs of inflammation, but perhaps with a draining sinus. TB meningitis causes subacute or chronic symptoms, with neck stiffness and changes in mental status, with or without cranial nerve palsies caused by inflammation at the base of the brain or increased intracranial pressure. Pericardial disease can be associated with the pain and friction rub of pericarditis or signs of pericardial tamponade. Patients with disseminated TB may have diffuse adenopathy and hepatic or splenic enlargement. A: AssessmentThe differential diagnosis of TB is extensive and depends in part on the degree of immunosuppression (as indicated by the CD4 cell count) of the individual. It includes a broad range of bacterial, mycobacterial, viral, and fungal infections in addition to noninfectious causes. A partial differential diagnosis of pulmonary TB includes: - Bacterial pneumonia
- Pulmonary Mycobacterium pneumonia (nontuberculous)
- Pneumocystis jiroveci pneumonia (PCP)
- Cryptococcus neoformans pneumonia/pneumonitis
- Pulmonary Kaposi sarcoma
- Toxoplasma pneumonitis
- Disseminated histoplasmosis
- Disseminated coccidioidomycosis
- Cytomegalovirus pneumonia
- Bronchogenic carcinoma
- Non-Hodgkin lymphoma
- Influenza
- Pulmonary embolus
- Chronic obstructive pulmonary disease
- Reactive airway disease
- Congestive heart failure
- Lactic acidosis
P: PlanDiagnostic EvaluationDuring the initial evaluation, check complete blood count (CBC) and differential, sputum gram stain, sputum AFB stain and culture (see below) blood cultures, and chest x-ray. For patients with lymphadenopathy, consider fine needle aspiration biopsy for bacterial and AFB stains and culture, and cytologic evaluation. For patients with meningitis or central nervous system abnormalities, perform lumbar puncture (LP) and cerebral spinal fluid (CSF) analysis including cell count, protein, glucose, AFB smear, AFB, bacterial and fungal cultures. If focal neurologic abnormalities are present, obtain computed tomography (CT) scan of the head to rule out mass lesion before doing the LP. Perform other diagnostic tests as suggested by the clinical presentation. Pulmonary TB can be associated with any chest x-ray appearance, including a normal x-ray. However, the chest x-ray classically demonstrates upper-lobe infiltrates with or without cavities. Patients with HIV-associated immunosuppression are more likely to have atypical chest x-rays, including absence of cavities, lower-lobe disease, hilar or mediastinal adenopathy, and pleural effusions. In disseminated TB, the chest x-ray may show a miliary pattern with small nodules ("millet seeds") scattered throughout both lungs. Suspected TB should be evaluated aggressively. Diagnosis of TB should include identification of the organism in stained sputum smears or stains of biopsied tissue and confirmed by culture or nucleic acid amplification (such as polymerase chain reaction). All positive cultures should be tested for drug susceptibility. Proof of the diagnosis is important because other opportunistic diseases can mimic TB, and other mycobacterial infections requiring different treatment can occur in HIV-infected persons. Drug susceptibility testing is necessary because improper treatment of drug-resistant TB will lead to treatment failure, more severe drug resistance within the patient, and increased risk of transmission of drug-resistant TB. A presumptive diagnosis of TB is made on acid-fast stains of expectorated sputum; 3 specimens should be sent for acid-fast staining and mycobacterial culture on 3 successive days (preferably first morning specimens). Sputum induction with nebulized saline can be used for patients who do not have spontaneous sputum production. Patients with suspected pulmonary TB and negative sputum smears should undergo bronchoscopy and transbronchial biopsy (which is more sensitive than bronchoalveolar lavage for TB). Young children cannot produce sputum, so gastric lavage on 3 successive mornings can be performed to obtain swallowed sputum for smear (although false-positive smears occur) and culture. The diagnosis of extrapulmonary TB generally requires microscopic examination of tissue and culture. An aspirate of a suspect lymph node will often be positive on smear, on histopathologic examination, and on culture. Specimens of organs with suspected TB can be obtained by CT-guided aspiration and biopsy, liver biopsy, bone marrow biopsy, "blind" needle biopsies of pleura or peritoneum, or thoracoscopy or laparoscopy-guided biopsies of pleura or peritoneum. At times an open surgical procedure is required to obtain appropriate specimens. Blood cultures for mycobacteria (using appropriate mycobacterial media rather than standard blood culture media) may be positive in disseminated TB; the technique is the same as in culturing blood for M avium complex organisms. Urine culture is used to diagnose renal TB, which is rare among HIV-infected persons. Some laboratories will perform a nucleic acid detection test on positive sputum smears and can confirm MTB in positive smears within 1 or a few days. The test is not sufficiently sensitive to use on negative smears, and drug sensitivity testing requires growth in culture. Initial growth may occur within 3-8 weeks. A nucleic acid probe can confirm a positive culture as MTB within a few days of culture growth; otherwise speciation may take several weeks. Susceptibility testing generally takes 3-4 weeks after the initial culture growth, depending on the laboratory procedures used. Note that a positive TST result indicates TB infection but does not prove active disease (see chapter Latent Tuberculosis). Similarly, a negative test can occur in HIV-infected persons with active TB and this was common among persons with disseminated TB prior to the HIV epidemic. A positive TST provides supporting evidence of TB disease; a negative test is not as informative in HIV-infected persons. Respiratory PrecautionsRespiratory infection control precautions should be implemented for HIV-infected patients with an undiagnosed chronic cough or undiagnosed inflammatory infiltrate on chest x-ray. Individual institutions have specific guidelines that should be followed; usually patients are housed in single negative-pressure rooms and persons entering the rooms are required to wear individual protective respirators. If 3 sputum smears are negative on acid-fast staining, or if a single deep specimen (bronchial lavage or tracheal aspirate) is smear negative, infectious TB is unlikely and respiratory precautions can be discontinued. Patients who are highly suspect for MTB and lack an alternative diagnosis should be kept on precautions and empiric treatment may be started. Persons who have responded to treatment for an alternative diagnosis (eg, bacterial pneumonia) and who cannot produce the requisite 3 sputum samples, may be released from the TB precautions. The impact of TB transmission is severe in a health care setting, where immunosuppressed persons may be exposed. Children aged <5 years and immunosuppressed persons in the home are at increased risk. TreatmentTreatment should be instituted when TB is considered likely and the proper specimens to determine the diagnosis have been obtained. It is ideal to have a positive smear and confirmation by nucleic acid amplification before to initiating treatment, but empiric treatment can be started after the specimens have been collected if the suspicion of TB is high, the patient is severely ill, or a positive smear is unlikely (eg, cerebrospinal fluid smears). Once the decision to treat is made and an appropriate regimen is selected, adherence becomes the most important issue. The treating clinician must ensure that the patient completes a full course of therapy. Therefore, it is strongly recommended that patients be referred to public health departments for TB treatment. Health departments usually provide free TB treatment and have specific resources and systems to promote adherence. All patients should receive directly observed therapy (DOT), whereby the taking of every dose of anti-TB medication is observed and documented. The intermittent TB therapies in Table 1 (regimens 1b, 2, and 3) were designed to simplify DOT. Clinical trials have documented that DOT with enhancements to maximize adherence improves the rate of completion of therapy and reduces mortality in HIV-infected TB patients. If the health department manages the TB treatment, the HIV clinician must coordinate with the health
department to do the following: 1) avoid drug interactions; 2) provide antiretroviral therapy (ART), if indicated, that does not conflict with the TB treatment; 3) ensure that immune reconstitution inflammatory syndrome (IRS) or incident opportunistic diseases are not misinterpreted as progression of TB; and 4) maximize adherence with the TB medications, ART, and any other medications. The U.S. guidelines for TB treatment in HIV-infected persons are shown in Table 1; dosages are given in Table 2. Four anti-TB drugs are administered for the first 2 months, and then 2 drugs are administered for an additional 4 months (if the organism is susceptible to standard medications). The initial phase of TB treatment usually consists of isoniazid, rifampin, pyrazinamide, and ethambutol; the continuation phase typically is simplified to isoniazid and rifampin. If drug resistance or MDR is suspected, more drugs can be used initially, and treatment should be directed by, or in consultation with, experts. Resistance may be suspected among persons who were exposed to TB in countries with high rates of endemic resistance, those who failed previous treatment, those who have used treatment erratically, those who may have had a specific exposure to drug-resistant TB, or those who were diagnosed during an MDR
outbreak. Treatment is extended in certain circumstances. Cavitary TB or TB in an HIV-infected person who remains sputum-culture positive after 2 months of treatment should be treated for a total of 9 months; bone and joint TB are treated for 6-9 months; and meningeal TB is treated for 9-12 months. If cultures obtained before treatment demonstrate drug resistance, the regimen and the duration of therapy may need to be changed. In patients with TB meningitis or pericarditis, and for persons with adrenal insufficiency, a course of corticosteroids is given in addition to specific anti-TB therapy. Considerations in pregnancyPyrazinamide has not been formally proven safe during pregnancy although no problems have been reported with its use during pregnancy. Some health departments in the United States avoid pyrazinamide in pregnant women and extend the continuation phase to 7 months. Others prescribe the standard regimens in Table 1 during pregnancy. Streptomycin and certain second-line drugs should be avoided during pregnancy. HIV-infected women in the United States are instructed not to breast-feed, so there are usually no issues regarding TB treatment of HIV-infected women during breast-feeding. |
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| Drugs | Interval and Doses (minimum duration) | Regimen | Drugs | Interval and Doses (minimum duration) | Range of Total Doses (minimum duration) | | 1. Preferred Regimen | | Isoniazid Rifampin* Pyrazinamide Ethambutol | 7 days/week for 56 doses or 5 days/week for 40 doses (8 weeks) | 1a. | Isoniazid Rifampin* | 7 days/week for 126 doses or 5 days/week for 90 doses (18 weeks)# | 182-130 doses (28 weeks) | | 1b. if CD4 count >100 cells/µL | Isoniazid Rifampin* | Twice weekly for 36 doses (18 weeks)** # | 92-76 doses (28 weeks) | | 2. Acceptable Alternative if CD4 >100 cells/µL | | Isoniazid Rifampin* Pyrazinamide Ethambutol | 7 days/week for 14 doses (2 weeks) followed by twice weekly for 12 doses (6 weeks) OR 5 days/week for 10 doses (2 weeks) followed by twice weekly for 12 doses (6 weeks) | 2. if CD4 count >100 cells/µL | Isoniazid Rifampin* | Twice weekly for 36 doses (18 weeks)** # | 62-58 doses (28 weeks) | | 3. Acceptable Alternative | | Isoniazid Rifampin* Pyrazinamide Ethambutol | 3 times weekly for 24 doses (8 weeks) | 3. | Isoniazid Rifampin* | 3 times weekly for 54 doses (18 weeks)# | 72 doses (28 weeks) |
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| | | Agent | Adults | Children | Adults | Children | Adults | Children | | Isoniazid* (tabs: 100 and 300 mg) | 5 mg/kg (300 mg max) | 10-15 mg/kg (300 mg max) | 15 mg/kg (900 mg max) | 20-30 mg/kg (900 mg max) | 15 mg/kg (900 mg max) | NA | | Rifampin** (caps 300 mg) | 10 mg/kg (600 mg max) | 10-20 mg/kg (600 mg max) | 10 mg/kg (600 mg max) | 10-20 mg/kg (600 mg max) | 10 mg/kg (600 mg max) | NA | | Pyrazinamide (tabs 500 mg) | 20-25 mg/kg (2 g max) | 10-30 mg/kg (2 g max) | 35-50 mg/kg (3 g max) | 10-30 mg/kg (2 g max) | 35-55 mg/kg (4 g max) | NA | | Ethambutol (tabs 100 and 400 mg) | 15-20 mg/kg (1,600 mg max) | 10-20 mg/kg (1 g max) | 20-30 mg/kg (2,400 mg max) | 10-20 mg/kg (1 g max) | 35-50 mg/kg (4,000 mg max) | NA | | Rifamate# (caps isoniazid 150 mg, rifampin 300 mg) | 2 caps daily | NA | NA | NA | NA | NA | | Rifater## (tabs isoniazid 50 mg, rifampin 120 mg, pyrazinamide 300 mg) | ≤44 kg: 4 tabs 45-54 kg: 5 tabs 55-90 kg: 6 tabs | NA | NA | NA | NA | NA |
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Treatment of pediatric patientsChildren are often treated with a 7-month continuation phase for a total treatment time of 9 months, although there are no data on this issue. Some experts avoid ethambutol in young children who cannot be tested for the adverse event of color blindness; others consider the risk so small with current ethambutol dosages that the drug can be included safely. Treatment of children for TB should be done in consultation with an expert. Coordinating with Antiretroviral TherapyART and TB treatment must be coordinated for both to be successful. Rifampin is a potent inducer of cytochrome p450 enzymes and has clinically important interactions with many medications, including certain antiretrovirals and oral contraceptives. Rifampin reduces the blood concentrations of nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs), but does not affect nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or the entry inhibitor enfuvirtide. Some NNRTIs and PIs cannot be used with rifampin while other require dose adjustment when coadministered (Table 3). Triple-nucleoside regimens can be administered safely during rifampin treatment but are less potent than other first-line antiretroviral (ARV) combinations. The safest ARV combination to use with rifampin is a 2-drug nucleoside backbone with efavirenz. Some clinicians increase the efavirenz dosage to 800 mg/day because efavirenz
blood concentrations may be reduced 25% by concomitant rifampin. Note that efavirenz is teratogenic; women who take efavirenz should avoid pregnancy by using birth control methods that are not affected by rifampin (preferably condoms plus injectable progestins or condoms plus an intrauterine device). |
| | | Nonnucleoside Reverse Transcriptase Inhibitors | | Efavirenz** | Rifampin dosage is unchanged; give efavirenz dosage of 600-800 mg daily | No change in efavirenz dosage; increase rifabutin to 450-600 mg 3 times daily | | Nevirapine | Generally not recommended; despite 25-50% reduction in nevirapine levels, 2 small studies claim standard dosages are effective | Use standard dosage of nevirapine; rifabutin 300 mg daily or 3 times weekly | | Delavirdine | Never combine | Never combine | | Unboosted Protease Inhibitors | | Ritonavir | May be used at standard dosages; limited clinical experience | Ritonavir at standard dosage; rifabutin 150 mg alternate days or 3 times weekly | | Amprenavir, fosamprenavir | Never combine | PIs at standard dosage; rifabutin 150 mg/day or 300 mg 3 times weekly | | Atazanavir | Never combine | Atazanavir at standard dosage; rifabutin 150 mg alternate days or 3 times weekly | | Indinavir | Never combine | Increase indinavir to 1,000 mg every 8 hours; rifabutin 150 mg/day or 300 mg 3 times weekly | | Nelfinavir | Never combine | Increase nelfinavir to 1,000 mg every 8 hours; rifabutin 150 mg/day or 300 mg 3 times weekly | | Ritonavir-Boosted Protease Inhibitors | | Lopinavir/ritonavir (Kaletra) | Lopinavir/ritonavir (3 caps twice daily) must be supplemented with additional ritonavir 300 mg twice daily; limited experience, not well tolerated | Standard dosage of lopinavir/ritonavir; decrease rifabutin to 150 mg alternate days or 3 times weekly | | Saquinavir/ritonavir | Should not be used because of high rates of hepatotoxicity | Standard dosage of lopinavir/ritonavir; decrease rifabutin to 150 mg alternate days or 3 times weekly | | All other ritonavir-boosted PIs | Should not be used (adequate dosing regimens not defined) | Standard dosage of PI/ritonavir; decrease rifabutin to 150 mg alternate days or 3 times weekly |
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Rifabutin may be substituted for rifampin to avoid rifampin-ARV interactions. Rifabutin has less marked effects on the pharmacokinetics of other drugs compared to rifampin, although its own blood concentrations can be affected by certain ARVs. See Table 3 for dosing recommendations for coadministration of rifabutin with ARVs. Rifabutin is expensive; some public health systems do not provide rifabutin as part of TB treatment and it generally is not available in resource-limited countries. The U.S. Food and Drug Administration characterizes rifabutin in pregnancy category B: it has been safe in animal studies of pregnancy but has not been proven safe in humans. For pregnant women who require both TB and ARV therapy, the use of rifabutin rather than rifampin allows the use of non-efavirenz-based ARV regimens. Persons who are already taking ART when TB treatment is begun should have their ARV regimens reassessed. The appropriate dosages of rifampin or rifabutin must be chosen and the ARV regimen may need to be modified, at least until the completion of TB treatment. In HIV/TB coinfected patients the optimal timing of ART initiation in relation to TB therapy is not known. For patients who are not taking ART at the time they start TB therapy, many specialists recommend postponing ART for the first 4-8 weeks of TB therapy. This strategy decreases the pill burden, adherence problems, the risk of drug adverse effects, and the risk of IRS (see below). Some experts recommend that persons with very low CD4 cell counts (<50-100 cells/µL) start ART 2 weeks after initiating TB treatment, although others believe that an increased risk of complications remains. International studies are under way, and others are planned, to inform this decision. Persons who do not require immediate ARV treatment (eg, those with CD4 counts >350 cells/µL) may be best served by completing TB treatment first and then reassessing the need for ARVs. Monitoring for efficacyIdeally, every dosing of anti-TB therapy is observed and documented by a health care agent or responsible individual. A member of the health care team should evaluate patients' adherence at least weekly during the initial phase or monthly during the continuation phase. If gaps in medication use occur, the cause must be evaluated and a plan to improve adherence must be implemented. During the treatment of pulmonary TB, monthly sputum specimens should be obtained for smear and culture until 2 sequential specimens are sterile on culture. Patients with extrapulmonary and disseminated TB are usually monitored clinically and with imaging studies. Biopsies are not repeated but other specimens (cerebrospinal and other body fluids) may be obtained for repeat laboratory study including acid-fast bacilli smear and culture, cell counts, and protein levels. Monitoring of patients with extrapulmonary and disseminated TB should be done in consultation with an expert. Managing immune reconstitution syndromePatients in the initial months of treatment for active TB who begin ART may experience a paradoxical increase in signs and symptoms of TB (fever, dyspnea, increased cough, enlarging lymph nodes, worsening chest x-ray findings, increased inflammation at other involved sites, or enlargement of central nervous system tuberculomas). In many cases, this phenomena is caused by an enhanced immune response against remaining MTB organisms because of immunologic improvement from ART. IRS often occurs within 2 weeks up to several months after ARVs are begun and is usually accompanied by a sharp decline in the HIV viral load and at least a 2-fold increase in the CD4 cell count. TB treatment failure (potentially due to an inappropriate treatment regimen, inadequate adherence, or drug resistance) must be ruled out and the possibility of drug toxicity should be considered. If IRS is diagnosed, TB and ARV treatment should be continued and symptoms should be managed with
nonsteroidal anti-inflammatory drugs, or in severe cases, with a short course of corticosteroids. See chapter Immune Reconstitution Syndrome.) Monitoring for toxicityAntituberculous medications may have significant adverse effects. Table 4 lists the most important adverse reactions reported for the commonly used anti-TB medications. Before initiating TB treatment, check complete blood count with platelet count, serum creatinine, liver function tests (aspartate aminotransferase [AST], alanine aminotransferase [ALT], bilirubin, alkaline phosphatase), and hepatitis B and C serology. Newly diagnosed TB patients with unknown HIV status should be encouraged to undergo testing for HIV infection. Thereafter, all patients taking TB therapy should be monitored monthly with a symptom review to assess possible toxicity. Although HIV-uninfected persons without risks for liver disease do not require routine laboratory monitoring, HIV/TB coinfected patients have a higher risk of drug toxicity. Laboratory monitoring may be repeated after 1 month of treatment and every 3 months thereafter, unless symptoms or laboratory abnormalities warrant more frequent testing. Persons with symptoms and AST or ALT elevations ≥3 times the upper limit of normal, and asymptomatic persons with aminotransferase elevations ≥5 times the upper limit of normal, should have therapy interrupted and should be managed thereafter in consultation with an expert. Patients should be monitored for isoniazid-induced peripheral neuropathy; this adverse effect is rare if pyridoxine is administered with isoniazid, as recommended (Table 2). Testing of visual acuity and red-green color discrimination is recommended at the start of therapy with ethambutol. Persons taking
standard ethambutol doses who have normal baseline examinationss should be asked monthly about visual disturbances. Those taking higher ethambutol dosages or prolonged ethambutol treatment (>2 months) should have periodic eye examinations for acuity and color discrimination. |
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| Isoniazid | | | - Hepatitis
- Peripheral neuropathy
- Drug fever
| | Rifampin | - Bilirubin elevations in the beginning of treatment
- Orange discoloration of urine and tears
- Liver enzyme elevations
| | - Hepatitis
- Pruritus
- Flu syndrome
- Drug fever
| | Pyrazinamide | | | | | Ethambutol | | | - Retrobulbar neuritis
- Periaxial ocular toxicity
| | Streptomycin | | - Cochlear toxicity
- Hypersensitivity reactions
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Patient Education- All patients with TB-positive sputum or bronchoscopy specimens can infect others with TB. All close contacts, especially children, should be screened for TB as soon as possible and given medication to prevent (or treat) active disease.
- The health department will be notified of each TB case and will provide the required follow-up care.
- Patients must take all medicines exactly as prescribed. If doses are missed, or if the medication is stopped and restarted, the TB bacteria can develop resistance to even the best medications and become even more dangerous. If patients are having trouble taking the medication on schedule, they should contact their health care providers immediately.
- If patients become ill, if their skin or eyes turn yellow, or if their urine darkens to a cola color, they should see their health care providers immediately.
- Patients must keep all follow-up appointments. Blood tests will be done regularly to be sure the liver is working well, and patients will be checked for medication adverse effects. They should show their health care providers all medications, vitamins, and supplements that they are taking so that the providers can check for drug interactions.
- Rifampin will make urine, sweat, and tears turn orange; this is not harmful. It will also stain plastic contact lens; patients should avoid wearing these if they are taking rifampin.
- Rifampin will cause birth control pills to fail. An alternate method of contraception should be used when the patient is under treatment.
- Alcohol should be avoided during treatment with TB drugs to avoid liver damage.
References- American Thoracic Society, Centers for Disease Control and Prevention, Infectious Diseases Society of America. Treatment of Tuberculosis. Am J Respir Crit Care Med. 2003 Feb 15;167(4):603-62. Available online at ajrccm.atsjournals.org/cgi/content/full/167/4/603. Accessed May 19, 2006.
- Blumberg HM, Leonard MK, Jasmer RM. Update on the treatment of tuberculosis and latent tuberculosis infection. JAMA. 2005 Jun 8;293(22):2776-84.
- Centers for Disease Control and Prevention. Acquired rifamycin resistance in persons with advanced HIV disease being treated for active tuberculosis with intermittent rifamycin-based regimens. Morb Mortal Wkly Rep. 2002 Mar 15;51(10):214-5.
- Centers for Disease Control and Prevention. Updated guidelines for the use of rifabutin or rifampin for the treatment and prevention of tuberculosis among HIV-infected patients taking protease inhibitors or nonnucleoside reverse transcriptase inhibitors. Morb Mortal Wkly Rep. 2000 Mar 10;49(9):185-9.
- Frieden T, ed. Toman's Tuberculosis: Case Detection, Treatment and Monitoring: Questions and Answers, 2nd ed. Geneva: World Health Organization; 2004. Accessed February 7, 2006.
- Harries A, Maher D, Graham S. TB/HIV: A Clinical Manual, 2nd ed. Geneva: World Health Organization; 2004. Accessed February 7, 2006.
- Iseman MD. Treatment of multidrug-resistant tuberculosis. N Engl J Med. 1993 Sep 9;329(11):784-91.
- Iseman MD. A Clinician's Guide to Tuberculosis. Philadelphia: Lippincott Williams & Wilkins; 2000.
- Reider H.L. Interventions for Tuberculosis Control and Elimination. 2002. International Union Against Tuberculosis and Lung Disease. Accessed February 7, 2006.
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