|Clinical Guide > Comorbidities and Complications > >M. tuberculosis|
Guide for HIV/AIDS Clinical Care, HRSA HIV/AIDS Bureau
In HIV-infected individuals, tuberculosis (TB) causes more deaths worldwide than any other condition. A biologic synergy exists between HIV and TB such that HIV-induced immunosuppression increases susceptibility to active TB infection, whereas active TB infection increases HIV progression and risk of death. The populations infected by these two pathogens overlap in many respects, creating epidemiologic synergy. Poverty, crowded living conditions, and inadequate interventions to reduce transmission and treat latent TB infection (LTBI) combine to enhance the transmission of both organisms.
In the United States, more than 60% of TB cases occur in foreign-born individuals, with the majority of these cases attributed to reactivation of LTBI. In 2010, only 8% of active TB cases occurred in patients known to be infected with HIV, and TB is a relatively infrequent AIDS-defining illness. Nevertheless, TB remains important to HIV clinicians in the United States because it can be highly infectious and challenging to diagnose, and because improper treatment may lead to drug resistance both in the infected patient and in individuals to whom that patient transmits. Although other conditions increase the risk of TB disease (e.g., malnutrition, diabetes, end-stage renal disease, pulmonary silicosis, and iatrogenic immunosuppressive drugs [especially inhibitors of tumor necrosis factor]), HIV infection remains an important risk factor.
TB is an infection caused by Mycobacterium tuberculosis complex. These organisms grow slowly and can be identified only with special staining techniques, a trait that led to the name "acid-fast bacteria." This chapter focuses on disease caused by M. tuberculosis (MTB); other chapters describe diagnosis and management of latent MTB infection (see chapter Latent Tuberculosis Infection) and diagnosis and management of disease caused by Mycobacteria avium (see chapter Mycobacterium avium Complex).
MTB most often causes a chronic pneumonia, but it can affect organs other than the lungs as well. The lung destruction caused by MTB may create cavities, similar to abscesses; these contain huge numbers of organisms. TB is transmitted almost always by persons with active pulmonary TB who release large numbers of organisms in their sputum. Patients with smear-positive sputum are the most infectious; however, transmission from patients with AFB smear-negative, culture-positive sputum has been well documented. Extrapulmonary tuberculosis is not generally considered contagious. Organisms are inhaled and infect the lung. In most people, the initial lung infection is contained by an effective immune response. It usually is asymptomatic but leads to foci in the lung (and sometimes in other organs) of latent TB, which may reactivate and cause active TB disease years later. Shortly after the onset of infection with MTB, before its containment in the lung by the immune system, organisms can spread to other organs and establish latent infection in those areas as well. Reactivation in these other organs can lead to local disease (e.g., in the lymph nodes, meninges, bone, pericardium, peritoneum or intestine, and urogenital tract).
Persons with impaired immunity, such as persons with HIV-associated immunosuppression and very young children, are at high risk of developing progressive primary TB at the time of initial MTB infection. Primary progressive MTB usually causes pulmonary disease, but also can cause meningitis or disseminated disease (blood, liver, spleen, lung, and other organs). Persons who have latent TB infection and then develop immunodeficiency are at high risk of developing reactivation disease. For example, compared with the 10% lifetime risk of developing active TB in immunologically normal persons, an HIV-infected person with latent TB has about a 10% chance each year of developing active disease. Even with immune reconstitution through antiretroviral therapy (ART) and a normalized CD4 cell count, HIV-infected patients remain at elevated risk of reactivation TB, compared with the background community risk for TB.
Classical pulmonary tuberculosis, with upper-lobe infiltrates and cavitary lesions, may occur in HIV-infected persons with relatively intact immunity. As the CD4 count decreases (particularly to <200 cells/µL), TB is more likely to manifest atypically in the chest (without cavitary disease) or with lower-lobe disease, adenopathy, pleural effusions, or interstitial or military infiltrates), and as extrapulmonary or multiorgan disease (particularly in lymph nodes, peritoneum, pericardium, and meninges). Granulomas may be seen in the tissues; in persons with advanced immunodeficiency, these may be poorly formed and non-caseating. Bone, joint, and urogenital TB are less-commonly associated with HIV-induced immunosuppression. Symptoms and signs in HIV-infected persons therefore can vary widely and can be difficult to distinguish from HIV-related opportunistic infections and malignancies.
Appropriate use of modern chemotherapy with rifampin-containing TB treatment applied to drug-susceptible MTB disease cures at least 95% of these patients, including those with HIV coinfection. However, drug resistance seriously reduces the cure rate. Drug resistance usually is caused by improper or erratic treatment, and is spreading rapidly and becoming more severe. Effective diagnosis and cure of drug-susceptible TB not only reduces the disease burden in the individual and reduces further transmission, it also is crucial to avoiding drug resistance.
MTB resistance to a single drug may extend or complicate treatment but usually does not prevent successful treatment of TB. Resistance to both isoniazid and rifampin, with or without resistance to other first-line drugs, is called multidrug resistance (MDR), and it makes treatment especially difficult. Extreme drug resistance (XDR) occurs when, in addition to isoniazid and rifampin resistance, there is resistance to specific second-line drugs: a fluoroquinolone plus an injectable agent (kanamycin, amikacin, or capreomycin). Treatment of drug-resistant TB should be managed by experts or in consultation with experts. MDR TB is uncommon in the United States; it occurred in 1.3% of cases in 2010, and the great majority of these were foreign-born patients (82.6%). XDR is very rare in the United States, with only 4 cases reported in 2010.
Effective antiretroviral treatment (ART) is a critical component of the care of persons with TB, and ART should be initiated or optimized in all persons with active TB, regardless of their current CD4 cell count.
Th is chapter will discuss the evaluation and management of TB in the United States and other high-income settings. For management of TB in resource-limited settings, see the relevant World Health Organization guidelines and other resources.
Persons with TB generally describe an illness lasting several weeks to months, associated with systemic features such as high fevers, night sweats, loss of appetite, and weight loss. These symptoms are nonspecific, but should raise the possibility of TB.
Risk factors for TB infection include known prior contact with an active case, exposure in congregate settings (such as homeless shelters and prisons, but also in health care facilities), travel or residence in countries with high rates of endemic TB, and birth in a TB-endemic county (more than half of foreign-born individuals diagnosed with TB in the United States originated from one of the following five countries: Mexico, the Philippines, Vietnam, India, or China). In the United States, persons with active or past substance-use disorders and persons of color are more likely than others to have had exposure to TB. History of a prior positive tuberculin skin test (TST) or interferon-gamma release assay (IGRA) result provides evidence of previous TB exposure; however, up to 35% of patients with active TB will have a negative TST or IGRA result (see chapter Latent Tuberculosis Infection). Risks for active TB disease include any degree of HIV-associated immunosuppression, immunosuppression associated with other diseases (e.g., leukemia, lymphoma) or caused by medical therapies (e.g., tumor necrosis factor-alpha blockers such as etanercept), and malnutrition.
Systemic signs of chronic disease and inflammation are common, including cough, 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 presents as subacute or chronic meningitis, with neck stiffness and changes in mental status. Symptoms may include cranial nerve palsies owing to inflammation at the base of the brain or increased intracranial pressure.
Pericardial disease can cause the pain and friction rub of pericarditis or signs of pericardial tamponade.
Infiltration of the bone marrow can produce pancytopenia.
Disseminated TB may cause diffuse adenopathy, hepatic or splenic enlargement, and abnormal liver function, although hepatic failure is rarely attributable to TB alone. Infection of the adrenal glands can cause adrenal insufficiency.
Note: If pulmonary TB is suspected, the patient should wear a mask while in the medical facility and the care provider should wear an N95 respiratory during the examination to reduce transmission risk.
The 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 the following:
Suspected TB should be evaluated aggressively.
Pulmonary TB can be associated with any chest X-ray appearance, including a normal X-ray image. However, the chest X ray classically demonstrates upper-lobe infiltrates with or without cavities. Patients with HIV infection (especially advanced HIV and low CD4 cell counts) are more likely to have atypical chest X-ray presentations, including absence of cavities, presence of 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.
TB should be diagnosed by identification of the organism in stained sputum smears or stains of tissue and confi rmed by culture or NAA test. All positive cultures should undergo drug susceptibility testing. Proof of the diagnosis is important because other opportunistic diseases can mimic TB, and mycobacterial infections other than TB (e.g., MAC) can occur; these require different treatment. TB drug susceptibility testing is necessary to ensure appropriate treatment, to reduce the risk of developing further TB drug resistance, and to decrease the risk of transmission of drug-resistant TB. Two to three specimens of expectorated sputum should be sent for acid-fast staining and mycobacterial culture. A presumptive diagnosis of pulmonary TB can be made if AFB are seen, but confirmation is required. Sputum induction with nebulized saline (e.g., by respiratory therapists) can be used for patients who do not have spontaneous sputum production. (Sputum induction has been successful in children, but for young children who cannot produce sputum, gastric lavage on three successive mornings can be performed to obtain swallowed sputum for smear [although false-positive results can occur] and culture.)
The U.S. Centers for Disease Control and Prevention (CDC) recommends NAA testing on at least one respiratory specimen (regardless of smear status) from each patient with signs and symptoms of pulmonary TB, if the NAA test result will alter management. The GenProbe MTD is currently the only NAA test approved by the U.S. Food and Drug Administration (FDA). The algorithm in Table 1 is recommended for interpretation of GenProbe test results.
Table 1. Nucleic Acid Amplification Testing and Interpretation Algorithm
Sensitivity of the GenProbe in smear-positive specimens is high but decreases to 50-80% in smear-negative, culture-positive specimens. The rapid identification of MTB facilitates appropriate respiratory infection control precautions, contact tracing, and immediate treatment of MTB. NAA tests also are useful in making a presumptive diagnosis in smear-negative patients who are suspected to have active pulmonary TB, pending culture results. However, these tests can yield false-positive results, particularly with persons in whom pulmonary TB is unlikely. Also, false negatives can occur in both smear-positive and smear-negative patients. GenProbe testing is not available in all laboratories and in some it is restricted to AFB smear-positive specimens.
The Xpert MTB/RIF is a rapid NAA test that is not yet FDA approved in the United States. The Xpert MTB/RIF identifies TB as well as rifampicin (RIF) resistance from a direct sputum sample. Data from high-prevalence TB settings show a sensitivity of >98% for TB in smear-positive specimens. Sensitivity in smear-negative specimens is 70% with a single test, and up to 90% with three tests, with a specificity of 99%. Other NAA tests can be used to rapidly identify clinically significant non-TB Mycobacteria such as MAC and M. kansasii. If a non-TB Mycobacterium is diagnosed, respiratory precautions can be discontinued, and treatment for the specific or suspected organism can be started.
In patients with suspected pulmonary TB, negative sputum microscopy or NAA results do not rule out TB; and consideration should be given to starting empiric TB treatment while further evaluation is undertaken.
A diagnosis of extrapulmonary TB generally requires an examination of infected tissue or body fluid by microscopy and culture. NAA testing for MTB and some other atypical Mycobacteria also can be performed on tissue and body fluids (such as CSF); specimens that are fresh or frozen generally are preferable to specimens preserved in formalin or a similar chemical. Specimens of organs with suspected TB can be obtained by peripheral lymph node aspiration, CT-guided or other guided aspiration and biopsy, liver biopsy, bone marrow biopsy, or thoracoscopy- or laparoscopy-guided biopsies of pleura or peritoneum. In some cases, surgery 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, particularly with advanced HIV disease; the technique is the same as in culturing blood for MAC organisms. Urine culture is used to diagnose renal TB, although this condition is rare among HIV-infected persons.
Initial growth of MTB on culture may occur within 3-8 weeks. A nucleic acid probe can confirm a positive culture as MTB within 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 what laboratory procedures are used. Rapid tests for diagnosis of drug resistance are available outside the United States (including line probe assays, Xpert MTB/RIF, nitrate reductase assay, and phage-based assays) but are not yet FDA approved. Some health departments have in-house assays for rifampin resistance. NAA tests for TB drug resistance are most efficient at screening for resistance against drugs for which a single mutation (e.g., rifampin) or a few mutations (e.g., isoniazid) are responsible for most clinically important drug resistance. Rapid assays to detect mutations that confer resistance to other first- and second-line drugs are in development.
Note that a positive TST or IGRA result confirms TB infection but does not prove active disease (see chapter Latent Tuberculosis). Similarly, a negative result may occur in up to 35% of HIV-infected persons with active TB and does not rule out TB disease. When a specific microbiologic diagnosis cannot be made or may be delayed (as with TB meningitis testing, for which CSF culture results may take weeks to obtain or may be negative), a positive TST or IGRA result can help support the diagnosis and implementation of therapy; however, a negative result on these tests does not rule out active TB.
Respiratory 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; patients usually are housed in single negative-pressure rooms and persons entering the rooms are required to wear protective respirators. Patients seen in the outpatient setting should wear a mask while in the medical facility, and providers should wear an N95 respirator when evaluating the patient. If three sputum smears yield negative results on AFB 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 may be kept on precautions and empiric treatment may be started, as transmission of TB from AFB smear-negative, culture-positive TB patients is well documented. Persons who have responded to treatment for an alternative diagnosis (e.g., bacterial pneumonia), and those who cannot produce the requisite three sputum samples, may be released from the TB precautions.
Th e impact of TB transmission is greater in a health care setting, where immunosuppressed persons may be exposed, than at home, where exposure has already occurred prior to the TB evaluation. Of course, children younger than age 5 and immunosuppressed persons in the home are at increased risk.
Treatment for TB should be instituted promptly when TB is considered likely and the proper specimens to prove the diagnosis have been obtained. It is ideal to have a positive smear result (and confirmation by NAA testing) prior to initiating treatment, but empiric treatment can be started while the initial specimens are collected from patients in whom the suspicion of TB is high, in severely ill persons, or in circumstances in which positive smear results are unlikely (e.g., suspected TB meningitis with AFB smear-negative CSF).).
Randomized trials have demonstrated that ART decreases mortality in HIV-infected persons with active TB regardless of initial CD4 cell count; thus, effective ART should be initiated or optimized in everyone with TB/HIV coinfection; see "Coordinating with antiretroviral therapy," below.
Adherence is the most important treatment issue once the decision to treat is made and an appropriate regimen is selected. It is the responsibility of the treating clinician to 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 can provide free TB treatment and have specific resources and systems to promote adherence. It is recommended that all patients receive directly observed therapy (DOT), an approach by which the taking of every dose of anti-TB medication is observed and documented. The intermittent therapies shown in Table 2 were designed to simplify DOT; however, twice-weekly regimens should not be used for persons with CD4 counts of <100 cells/µL. Once-weekly regimens with rifapentine should not be used for anyone with HIV infection.
Clinical trials have documented that DOT with enhancements to maximize adherence not only improves the rate of completion of therapy but also reduces mortality among HIV-infected TB patients. If a health department manages the TB treatment, the HIV clinician must coordinate with the health department for the following reasons: 1) to coordinate TB and HIV treatment regimens; 2) to avoid or adjust for drug interactions; 3) to assist the health department in avoiding diagnostic or treatment confusion in the event of immune reconstitution inflammatory syndrome (IRIS) or incident opportunistic diseases; and 4) to maximize adherence with the TB medications, ART, opportunistic infection treatment or prophylaxis, and any other medications.
Four anti-TB drugs are administered for the first 2 months, then two 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 or rifabutin (see below), pyrazinamide, and ethambutol; the continuation phase typically is simplified to isoniazid and rifampin. Pyridoxine (vitamin B6) at a dosage of 10-50 mg per day usually is included to minimize the risk of isoniazid-induced peripheral neuropathy. If drug resistance or MDR is suspected, more drugs can be used initially, and treatment should be directed by experts. Resistance may be suspected among persons exposed to TB in countries with high rates of endemic resistance, those for whom previous treatment has failed, those who have been on and off treatment erratically, those who may have had a specific exposure to drug-resistant TB, and those who have been diagnosed during an outbreak.
In certain circumstances, treatment duration is extended. In cavitary TB or TB in an HIV-Infected person that remains sputum culture positive after 2 months of treatment, the twodrug continuation phase should be extended to 7 months for a total treatment course of 9 months. For extrapulmonary TB in HIV-Infected persons, a 6- to 9-month course of treatment is recommended. Exceptions include meningeal TB and bone or joint TB, which are treated for 9-12 months. If cultures obtained prior to treatment demonstrate drug resistance, the regimen and the duration of therapy may need to be changed.
For TB meningitis or pericarditis, a course of corticosteroids may be given in addition to specific anti-TB therapy: dexamethasone 0.3-0.4 mg/kg/day tapered over the course of 6-8 weeks or prednisone 1 mg/kg/day for 3 weeks followed by a taper over the course of 3-5 weeks. For adrenal insufficiency, replacement corticosteroids should be given.
Pyrazinamide has not been formally proven safe for use during pregnancy; however, it is used during pregnancy in many countries and there have been no reports of problems. Some health departments in the United States avoid the use of pyrazinamide for pregnant women and extend the continuation phase to 7 months, whereas others prescribe the standard regimens shown 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 usually are no issues regarding TB treatment of HIV-infected women during breast-feeding. ART should be started as early as possible; consult with an expert.
Table 2. Recommended Dosages of First-Line Antituberculosis Drugs for Adults*
ART and TB treatment must be coordinated for both to be successful. ART is indicated for all adults and adolescents with active TB, and both metaanalyses and randomized trials have demonstrated reduction in mortality when ART is combined with anti-TB chemotherapy.
The optimal timing of ART initiation in relation to TB treatment has been established with several randomized controlled trials. Adults and adolescents with active TB and CD4 counts of <50 cells/µL should start ART within 2 weeks of starting TB treatment. Those with CD4 counts of 50-200 cells/µL should start ART within 2-4 weeks, particularly if they have severe disease, and those with higher CD4 counts should start ART within 8-12 weeks of starting TB therapy, if possible. ART should not be delayed until after completion of TB treatment, even in patients with high CD4 cell counts, owing to the increased risk of mortality with delayed ART initiation. In all cases, TB treatment should be started immediately.
Timing of ART initiation in CNS TB infection is not clear. In one randomized trial, there was not a mortality benefit to starting ART at 2 weeks after TB treatment initiation compared with starting after 2 months of TB treatment, and more severe adverse events occurred in the earlier ART arm. Given the capacity for close monitoring that exists in the United States, many experts recommend initiating ART as with non-CNS TB.
Although paradoxical immune responses (i.e., "immune reconstitution inflammatory syndrome," see below) may be more common in patients who start ART earlier in the course of TB treatment, IRIS generally is not fatal.
Drug interactions between TB medications and ARVs may require dosage adjustments or modifications in treatment (see Table 3). Rifampin is a potent inducer of cytochrome P450 enzymes and has many clinically important drug interactions. It reduces the blood levels of nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), the integrase inhibitor raltegravir, and the CCR5 antagonist maraviroc, but does not affect nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs) or the fusion inhibitor enfuvirtide. Triple-nucleoside regimens can be administered safely during rifampin treatment but are less potent than first-line ARV combinations and generally are not recommended. The safest ARV combination to use with rifampin is a two-drug NRTI backbone with efavirenz (see Table 3). The FDA recommends increasing the efavirenz dosage to 800 mg/day for patients weighing >60 kg because efavirenz blood levels may be reduced 25% by concomitant rifampin. However, the majority of available clinical data suggest that that the standard efavirenz dosage of 600 mg/day is appropriate for rifampin coadministration, particularly in African-American and Asian populations. Limited clinical data support the use of nevirapine at standard dosages in combination with rifampin. This is not a favored approach because nevirapine levels are reduced up to 50% when combined with rifampin. In one study, 20% of patients on ARV and TB treatment with rifampin had trough nevirapine levels that were below target, although they achieved the same rates of HIV RNA suppression as patients on efavirenz.
To avoid rifampin-ARV interactions, rifabutin typically is used in place of rifampin. Rifabutin has fewer marked effects on the pharmacokinetics of other drugs, although its own blood concentrations can be affected by certain ARVs. Dosing recommendations for rifabutin with ARVs are found in Table 3. Acquired rifamycin resistance has been reported with coadministration of rifabutin with protease inhibitors, leading to the recommendation that the rifabutin dosage be at least 150 mg daily when given with ritonavir-boosted PIs and that monitoring of serum rifabutin levels be considered. Rifabutin is expensive; some public health systems do not provide rifabutin as part of TB treatment and it often is not available in resource-limited countries. The FDA characterizes rifabutin in pregnancy category B: it has been safe in animal studies of pregnancy but has not been proven safe for 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 on ART when TB treatment is begun must have their ARV regimens reassessed; the appropriate dosages of rifampin or rifabutin must be chosen or the ARV regimen must be modified, at least until completion of TB treatment (see Table 3).
Table 3. Interactions Between Antiretroviral Medications and Rifampin or Rifabutin: Contraindicated Combinations and Dosage Adjustments*
Ideally, every dose of anti-TB therapy is observed and documented by a health care agent or responsible individual. Patients' adherence should be evaluated by a health care team member at least weekly during the initial phase of treatment and at least weekly 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.
In treatment of pulmonary TB, monthly sputum specimens should be obtained for smear and culture until two sequential specimens are sterile on culture. Patients with extrapulmonary and disseminated TB usually are monitored clinically and with imaging studies. Biopsies are not repeated but other specimens (CSF and other body fluids) may be obtained for repeat AFB smear and culture. Monitoring of patients with extrapulmonary and disseminated TB should be done in consultation with an expert.
Patients on 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 CNS tuberculomas). These often are attributable to an enhanced immune response against remaining MTB organisms that occurs because of immunologic improvement from ART. IRIS may occur at any point from within 2 weeks up to several months after ART is initiated. TB treatment failure (potentially owing to an inappropriate treatment regimen, inadequate adherence, or drug resistance) must be ruled out, and the possibility of drug toxicity should be considered. In addition, new presentation of opportunistic infection or malignancies should be considered. Paradoxical IRIS is a clinical diagnosis, and it can be made only after alternative diagnoses are excluded. If IRIS is diagnosed, TB and HIV treatment should be continued and symptoms can be managed with nonsteroidal antiinflammatory drugs or, in severe cases, with corticosteroids. (See chapter Immune Reconstitution Inflammatory Syndrome.)
Anti-TB medications may have significant adverse effects. The most important adverse reactions reported for the commonly used anti-TB medications are listed in Table 4. The most frequent toxicities of first-line TB medications include hepatic enzyme elevations. Before initiating TB treatment, conduct a complete blood count with platelet count, serum creatinine count, 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 tested for HIV infection.
Patients should be monitored monthly with a symptom review to assess possible toxicity, and laboratory tests should be performed if symptoms suggest adverse effects. For patients with liver disease, it may be prudent to perform routine laboratory monitoring after 1 month on treatment and every 3 months thereafter. Persons with symptoms and aminotransferase 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. Testing of visual acuity and red-green color vision is recommended at the start of therapy with ethambutol. Persons on standard ethambutol dosages with normal baseline examinations should be asked monthly about visual disturbances. Patients on higher ethambutol dosages and those who have been on ethambutol for more than 2 months should have periodic eye examinations for acuity and color discrimination.
Table 4. Adverse Events Associated with Common Anti-TB Medications
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