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Myco b acte ri u m tu be rcu I osis I nfection Agent Adverse Effects Notes First-Line Medications lsoniazid Rash; Iiver enzyme elevation; hepatitis; Hepatitis risk increases with age and alcohol consumption. peripheral neuropathy; lupus-like furidoxine may prevent peripheral neuropathy. Adjust for syndrome kidney injury. hTrazinamide Hepatitis; rash; Gl upse! hyperuricemia May make glucose control more difficult in patients with diabetes. Adjust for kidney injury. Rifampin Hepatitis; rash; Gl upset Contraindicated or used with caution when administered with protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Do not administer to patients also taking saquinavir/ritonavir. Colors body fluids orange. Rifabutin Rash; hepatitis; thrombocytopenia; Dose adjustment required if taken with protease inhibitors or severe arthralgia; uveitis; leukopenia non nucleoside reverse tra nscri ptase i n h i bitors. Mon itor for decreased antiretroviral activity and for rifabutin toxicity. Rifapentine Similarto rifampin Contraindicated in patients who are HIV positive (unacceptable rate of fail ure/relapse). Ethambutol Optic neuritis; rash Baseline and periodic tests of visual acuity and color vision. Patients are advised to call immediately if visual acuity or color vision changes. Adjust for kidney injury. Second-Line Medications" Streptomycin Auditory, vestibular, and kidney toxicity Avoid or reduce dose in adults >59 years. Monitor hearing and kidney function. Adjust dose depending on kidney function. Cycloserine Psychosis; convu lsions; depression; Pyridoxine may decrease CNS adverse effects. Measure drug headaches; rash; drug interactions serum levels. Capreomycin Kidney, vestibulat and auditory toxicity Monitor hearing and kidney function. Adjust dose depending on kidney function. Ethionamide Gl upset; hepatotoxicity; hypersensitivity May cause hypothyroidism.

Agent Adverse Effects Notes First-Line Medications lsoniazid Rash; Iiver enzyme elevation; hepatitis; Hepatitis risk increases with age and alcohol consumption. peripheral neuropathy; lupus-like furidoxine may prevent peripheral neuropathy. Adjust for syndrome kidney injury. hTrazinamide Hepatitis; rash; Gl upse! hyperuricemia May make glucose control more difficult in patients with diabetes. Adjust for kidney injury. Rifampin Hepatitis; rash; Gl upset Contraindicated or used with caution when administered with protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Do not administer to patients also taking saquinavir/ritonavir. Colors body fluids orange. Rifabutin Rash; hepatitis; thrombocytopenia; Dose adjustment required if taken with protease inhibitors or severe arthralgia; uveitis; leukopenia non nucleoside reverse tra nscri ptase i n h i bitors. Mon itor for decreased antiretroviral activity and for rifabutin toxicity. Rifapentine Similarto rifampin Contraindicated in patients who are HIV positive (unacceptable rate of fail ure/relapse). Ethambutol Optic neuritis; rash Baseline and periodic tests of visual acuity and color vision. Patients are advised to call immediately if visual acuity or color vision changes. Adjust for kidney injury. Second-Line Medications" Streptomycin Auditory, vestibular, and kidney toxicity Avoid or reduce dose in adults >59 years. Monitor hearing and kidney function. Adjust dose depending on kidney function. Cycloserine Psychosis; convu lsions; depression; Pyridoxine may decrease CNS adverse effects. Measure drug headaches; rash; drug interactions serum levels. Capreomycin Kidney, vestibulat and auditory toxicity Monitor hearing and kidney function. Adjust dose depending on kidney function. Ethionamide Gl upset; hepatotoxicity; hypersensitivity May cause hypothyroidism. Kanamycin and amikacin Auditory, vestibular, and kidney toxicity Not approved by the FDAfoTTB treatment. Monitor vestibulal hearing, and kidney function. Levofloxacin, moxifloxaci n Gl upset; dizziness; hypersensitivity; Not approved by the FDA for TB treatment. Should not be drug interactions used in children. Pa ra-am inosalicyl ic acid Gl upset; hypersensitivity; hepatotoxicity May cause hypothyroidism, especially if used with ethionamide. Measure liver enzyme levels. Bedaquiline Nausea; joint pain; headache; elevated FDA-approved oral agent for MDR pulmonary TB treatment; a m i notra nsferase levels; hemoptysis; indicated for combination therapy when other alternatives prolonged OT interval are not available. Novel mechanism of action inhibits mycobacteria I adenosi ne triphosphate synthase. Shou ld be given as directly observed therapy. Pretomanid Peripheral neuropathy; anemia; Gl upset; FDA-approved nitroimidazole, a novel oral agent, for XDR-TB elevated liver enzyme levels; headache; or nonresponsive MDR-TB in combination with bedaquiline hypoglycemia; rash; hyperamylasemia; and linezolid. visual impairment; diarrhea

Kanamycin and amikacin Auditory, vestibular, and kidney toxicity Not approved by the FDAfoTTB treatment. Monitor vestibulal hearing, and kidney function. Levofloxacin, moxifloxaci n Gl upset; dizziness; hypersensitivity; Not approved by the FDA for TB treatment. Should not be drug interactions used in children. Pa ra-am inosalicyl ic acid Gl upset; hypersensitivity; hepatotoxicity May cause hypothyroidism, especially if used with ethionamide. Measure liver enzyme levels. Bedaquiline Nausea; joint pain; headache; elevated FDA-approved oral agent for MDR pulmonary TB treatment; a m i notra nsferase levels; hemoptysis; indicated for combination therapy when other alternatives prolonged OT interval are not available. Novel mechanism of action inhibits mycobacteria I adenosi ne triphosphate synthase. Shou ld be given as directly observed therapy. Pretomanid Peripheral neuropathy; anemia; Gl upset; FDA-approved nitroimidazole, a novel oral agent, for XDR-TB elevated liver enzyme levels; headache; or nonresponsive MDR-TB in combination with bedaquiline hypoglycemia; rash; hyperamylasemia; and linezolid. visual impairment; diarrhea CNS = central nervous system; Ql = g6strointestinal; MDR = multidrug resistant; TB = tuberculosis; XDR = extensively drug resistant. "Use these drugs in consultation with a clinician experienced in the management of drug-resistant TB.

Kanamycin and amikacin Auditory, vestibular, and kidney toxicity Not approved by the FDAfoTTB treatment. Monitor vestibulal hearing, and kidney function. Levofloxacin, moxifloxaci n Gl upset; dizziness; hypersensitivity; Not approved by the FDA for TB treatment. Should not be drug interactions used in children. Pa ra-am inosalicyl ic acid Gl upset; hypersensitivity; hepatotoxicity May cause hypothyroidism, especially if used with ethionamide. Measure liver enzyme levels. Bedaquiline Nausea; joint pain; headache; elevated FDA-approved oral agent for MDR pulmonary TB treatment; a m i notra nsferase levels; hemoptysis; indicated for combination therapy when other alternatives prolonged OT interval are not available. Novel mechanism of action inhibits mycobacteria I adenosi ne triphosphate synthase. Shou ld be given as directly observed therapy. Pretomanid Peripheral neuropathy; anemia; Gl upset; FDA-approved nitroimidazole, a novel oral agent, for XDR-TB elevated liver enzyme levels; headache; or nonresponsive MDR-TB in combination with bedaquiline hypoglycemia; rash; hyperamylasemia; and linezolid. visual impairment; diarrhea CNS = central nervous system; Ql = g6strointestinal; MDR = multidrug resistant; TB = tuberculosis; XDR = extensively drug resistant. "Use these drugs in consultation with a clinician experienced in the management of drug-resistant TB. agents (isoniazid, rifampin, pyrazinamide, and ethambutol). given daily for 2 months, followed by a continuation phase This becomes increasingly important because of the advent of of isoniazid plus rifampin daily, usually for 4 months MDR and XDR tuberculosis. If rifampin resistance has been (Table 22). detected during NAAT assessment, in vitro susceptibilities Directly observed therapy, generally through the local to first-line and second-Iine agents should be performed health department, must be used when treatment is (Table 21). administered less than 7 days per week. Sputum speci- The American Thoracic Society/CDC guidelines published mens should be evaluated at 1- and 2-month intervals to in 2016 recommend 6 to 9 months of treatment in patients with assess for efficacy. In addition, clinical assessment and drug-susceptible active tuberculosis. A four-drug regimen is Iaboratory testing (complete blood count, liver chemistry

agents (isoniazid, rifampin, pyrazinamide, and ethambutol). given daily for 2 months, followed by a continuation phase This becomes increasingly important because of the advent of of isoniazid plus rifampin daily, usually for 4 months MDR and XDR tuberculosis. If rifampin resistance has been (Table 22). detected during NAAT assessment, in vitro susceptibilities Directly observed therapy, generally through the local to first-line and second-Iine agents should be performed health department, must be used when treatment is (Table 21). administered less than 7 days per week. Sputum speci- The American Thoracic Society/CDC guidelines published mens should be evaluated at 1- and 2-month intervals to in 2016 recommend 6 to 9 months of treatment in patients with assess for efficacy. In addition, clinical assessment and drug-susceptible active tuberculosis. A four-drug regimen is Iaboratory testing (complete blood count, liver chemistry 36

Mycob acte ri u m tu be rculosis I nfection (HIV chronic hepatitis B or C infections, alcohol abuse, Management pregnancy, concurrent hepatotoxic drugs, or underlying When suitable antimicrobial therapy is administered and liver disease). taken appropriately, clinical trials demonstrate clinical and In pregnant women with LTBI, a 6- to 9-month regi- microbiologic cure rates of approximately 95%. Therapy men of isoniazid plus pyridoxine may be offered; however, depends on several factors, including the classification of some experts prefer to defer therapy until after delivery, infection (latent versus active), pulmonary versus extrapulmo- unless the patient is at high risk of developing active nary infection, and patient adherence. infection owing to immunocompromise, including HIV infection. Treatment of Latent Tuberculosis All patients who have a positive IGRA or a positive TST f,EY POIf,T5 should be evaluated for active disease, with a full medical . All patients with latent tuberculosis should be screened history physical examination, and chest radiography, and be for HIV infection. screened for HIV infection. If no sign of active infection is o Recommended treatment regimens for latent tubercu- present, all patients should be offered treatment for LTBI. losis infection include isoniazid plus rifapentine once The 2020 CDC guidelines include five different treatment weekly for 3 months, rifampin daily for 4 months, or regimens (Table 20). Pyridoxine is recommended in patients isoniazid plus rifampin daily for 3 months. who will receive isoniazid and are at risk for peripheral neuropathy (diabetes mellitus, chronic kidney disease, mal- nutrition, HIV infection, and alcoholism). Baseline and Treatment of Active Tuberculosis monthly monitoring of liver chemistry tests are not rou- When active tuberculosis is verified, in vitro susceptibility tinely required unless patients are at risk for hepatotoxicity testing of the initial isolate should be done for the first-line

(HIV chronic hepatitis B or C infections, alcohol abuse, Management pregnancy, concurrent hepatotoxic drugs, or underlying When suitable antimicrobial therapy is administered and liver disease). taken appropriately, clinical trials demonstrate clinical and In pregnant women with LTBI, a 6- to 9-month regi- microbiologic cure rates of approximately 95%. Therapy men of isoniazid plus pyridoxine may be offered; however, depends on several factors, including the classification of some experts prefer to defer therapy until after delivery, infection (latent versus active), pulmonary versus extrapulmo- unless the patient is at high risk of developing active nary infection, and patient adherence. infection owing to immunocompromise, including HIV infection. Treatment of Latent Tuberculosis All patients who have a positive IGRA or a positive TST f,EY POIf,T5 should be evaluated for active disease, with a full medical . All patients with latent tuberculosis should be screened history physical examination, and chest radiography, and be for HIV infection. screened for HIV infection. If no sign of active infection is o Recommended treatment regimens for latent tubercu- present, all patients should be offered treatment for LTBI. losis infection include isoniazid plus rifapentine once The 2020 CDC guidelines include five different treatment weekly for 3 months, rifampin daily for 4 months, or regimens (Table 20). Pyridoxine is recommended in patients isoniazid plus rifampin daily for 3 months. who will receive isoniazid and are at risk for peripheral neuropathy (diabetes mellitus, chronic kidney disease, mal- nutrition, HIV infection, and alcoholism). Baseline and Treatment of Active Tuberculosis monthly monitoring of liver chemistry tests are not rou- When active tuberculosis is verified, in vitro susceptibility tinely required unless patients are at risk for hepatotoxicity testing of the initial isolate should be done for the first-line TABLE 2S. Treatment Regimens for LatentTuberculosis lnfection Priority Rank" Regimen Frequency Duration Doseb Total Doses Preferred lsoniazid plus Once weekly, directly 3 months lsoniazidd: 15 mg/kg rounded up to the 12 rifapentine' observed therapy nearest 50 or 100 mg; 900 mg maximum Rifapentine': 10.0-14.0 kg:300 mg 14.1-25.0 kg: 450 mg 25.1-32.0 kg:600 mg 32.1-49.9 kg: 750 mg >50.0 kg:900 mg maximum Preferred Rifampinr Daily 4 months 10 mg/kg 120

TABLE 2S. Treatment Regimens for LatentTuberculosis lnfection Priority Rank" Regimen Frequency Duration Doseb Total Doses Preferred lsoniazid plus Once weekly, directly 3 months lsoniazidd: 15 mg/kg rounded up to the 12 rifapentine' observed therapy nearest 50 or 100 mg; 900 mg maximum Rifapentine': 10.0-14.0 kg:300 mg 14.1-25.0 kg: 450 mg 25.1-32.0 kg:600 mg 32.1-49.9 kg: 750 mg >50.0 kg:900 mg maximum Preferred Rifampinr Daily 4 months 10 mg/kg 120 I Maximum dose:600 mg Preferred lsoniazid plus Daily 3 months lsoniazidd: 5 mg/kg;300 mg maximum 90 rifampin' Rifampin: 10 mg/kg; 600 mg maximum Alternativeg lsoniazid' Daily 6 months 5 mg/kgd 180 Maximum dose:300 mg Alternative lsoniazid' Daily 9 months 5 mg/kgd 270 Maximum dose:300 mg

I Maximum dose:600 mg Preferred lsoniazid plus Daily 3 months lsoniazidd: 5 mg/kg;300 mg maximum 90 rifampin' Rifampin: 10 mg/kg; 600 mg maximum Alternativeg lsoniazid' Daily 6 months 5 mg/kgd 180 Maximum dose:300 mg Alternative lsoniazid' Daily 9 months 5 mg/kgd 270 Maximum dose:300 mg efficacy but concerns regarding longer treatment duration; lower completion rates, and therefore lower effectiveness. bDoses listed are for adults. 'lncluding H|V-positive persons, as drug interactions allow. dlsoniazid is formulated as 100-mg and 300-mg tablets. "Rifapentine is {ormulated as 150-mg tablets in blister packs that should be kept sealed until use. rNo evidence reported in H|V-positive persons. sstrong recommendation forthose persons unabletotake a preferred regimen (e.g., because of drug intolerabilityordrug-drug interactions). AssociationandCDC,2020.MMWRRecommRep.2020;69:1-11. IPMtD:32053584] doi:10.15585/mmwr.116901a1 35

Nontuberculous Mycobacterial lnfections tuberculosis by performing chest radiography and simultane- TABLE 23. Classification of Common Nontuberculous ous TST or IGRA before beginning this therapy. All patients Mycobacteria should receive treatment for tuberculosis (ffgf or active) if Slow-Growing Mycobacteria identified, although LTBI treatment does not eliminate risk for Itrl. kansasii active mycobacterial infection in this population. M. marinum I(EY POIHT M. gordonae . Before initiating treatment with tumor necrosis factor M. scrofulaceum inhibitors, all patients should be screened for active or ltrl. avium complex (including M. chimaera) latent tuberculosis; those diagnosed should receive tuberculosis treatment to reduce the risk of reactivation M. ulcerans and death from disseminated disease. M. xenopi lVl. simiae

tuberculosis by performing chest radiography and simultane- TABLE 23. Classification of Common Nontuberculous ous TST or IGRA before beginning this therapy. All patients Mycobacteria should receive treatment for tuberculosis (ffgf or active) if Slow-Growing Mycobacteria identified, although LTBI treatment does not eliminate risk for Itrl. kansasii active mycobacterial infection in this population. M. marinum I(EY POIHT M. gordonae . Before initiating treatment with tumor necrosis factor M. scrofulaceum inhibitors, all patients should be screened for active or ltrl. avium complex (including M. chimaera) latent tuberculosis; those diagnosed should receive tuberculosis treatment to reduce the risk of reactivation M. ulcerans and death from disseminated disease. M. xenopi lVl. simiae M. malmoense Prevention M. szulgai From the public health perspective, the best way to prevent M. asiaticum tuberculosis is to diagnose, isolate, and treat infection rap- idly until patients are considered noncontagious and the Rapidly Growing Mycobacteria disease is cured. In hospitalized patients with suspected or M. abscessus documented tuberculosis, airborne precautions should be M. chelonae implemented. It/|. fortuitum CDC guidelines recommend criteria to determine if a patient is no longer contagious and a possible public health threat. These include appropriate antimicrobial therapy for at organisms to species level. American Thoracic Society (ATS) least 2 weeks, clinical improvement of signs and symptoms, guidelines (updated in 2020) recommend fulfillment of clini- and three negative sputum smears collected at least B hours cal, radiologic, and microbiologic criteria to diagnose an NTM apart, with one being an ear$-morning specimen. Patients pulmonary infection. Treatment is recommended for patients with negative smear results are less contagious, although they meeting diagnostic criteria, especially if acid-fast sputum may still have tuberculosis. smears are positive and/or cavitary lung disease is present. KEY POII{T Most NTM infections require prolonged treatment with multi- . Guidelines for determining a patient with tuberculosis ple antimicrobials; susceptibilities and ATS guidelines should is no longer contagious include appropriate antimicro- be used to guide therapy. bial therapy for at least 2 weeks, clinical improvement KEY POITTS in signs and symptoms, and three negative sputum . Risk factors for nontuberculous mycobacteria infections smears collected at least 8 hours apart. include immunocompromise, chronic lung disease, and postoperative status; additionally, health care-associ- ated Mycobacterium chimaera infections have been Nontuberculous associated with heater-cooler units used during cardiac Mycobacteria I I nfections surgery. o Antibiotic susceptibility varies among species, so iden- Nontuberculous mycobacteria (NTM) comprise species other tifying nontuberculous mycobacterial organisms to a than My cobacterium tuberculosis complex and My cobacterium species level is important. leprae. NTM are divided into slow and rapid growers (Table 23). These organisms are found in water, soil, domestic and wild animals, milk, and food products. They can be colonizers, par- ticular$ in the airways of persons with chronic lung disease, Mycobacterium avium and cause a spectrum of infections (Table 2a). Complex lnfection Risk factors for NTM infections include immunocompro- Mycobacterium auiumcomplex is a common cause of chronic mise, chronic lung disease, and postoperative status. lung infection worldwide. Cavitary lung disease is seen classi- NTM diagnosis is difficult because a positive culture result caliy in White, middle-aged, or older adult men with underly from a nonsterile site without evidence of disease may reflect ing lung disease. Disseminated infection occurs predomi colonization rather than infection. However, when recovered nantly in patients with HIV and CD4 cell counts less than from a sterile site, active infection is likely. Because antibiotic 50/pL. The clinical presentation consists of fever, night sweats, susceptibility among species varies, it is important to identify weight loss, and gastrointestinal symptoms.

M. malmoense Prevention M. szulgai From the public health perspective, the best way to prevent M. asiaticum tuberculosis is to diagnose, isolate, and treat infection rap- idly until patients are considered noncontagious and the Rapidly Growing Mycobacteria disease is cured. In hospitalized patients with suspected or M. abscessus documented tuberculosis, airborne precautions should be M. chelonae implemented. It/|. fortuitum CDC guidelines recommend criteria to determine if a patient is no longer contagious and a possible public health threat. These include appropriate antimicrobial therapy for at organisms to species level. American Thoracic Society (ATS) least 2 weeks, clinical improvement of signs and symptoms, guidelines (updated in 2020) recommend fulfillment of clini- and three negative sputum smears collected at least B hours cal, radiologic, and microbiologic criteria to diagnose an NTM apart, with one being an ear$-morning specimen. Patients pulmonary infection. Treatment is recommended for patients with negative smear results are less contagious, although they meeting diagnostic criteria, especially if acid-fast sputum may still have tuberculosis. smears are positive and/or cavitary lung disease is present. KEY POII{T Most NTM infections require prolonged treatment with multi- . Guidelines for determining a patient with tuberculosis ple antimicrobials; susceptibilities and ATS guidelines should is no longer contagious include appropriate antimicro- be used to guide therapy. bial therapy for at least 2 weeks, clinical improvement KEY POITTS in signs and symptoms, and three negative sputum . Risk factors for nontuberculous mycobacteria infections smears collected at least 8 hours apart. include immunocompromise, chronic lung disease, and postoperative status; additionally, health care-associ- ated Mycobacterium chimaera infections have been Nontuberculous associated with heater-cooler units used during cardiac Mycobacteria I I nfections surgery. o Antibiotic susceptibility varies among species, so iden- Nontuberculous mycobacteria (NTM) comprise species other tifying nontuberculous mycobacterial organisms to a than My cobacterium tuberculosis complex and My cobacterium species level is important. leprae. NTM are divided into slow and rapid growers (Table 23). These organisms are found in water, soil, domestic and wild animals, milk, and food products. They can be colonizers, par- ticular$ in the airways of persons with chronic lung disease, Mycobacterium avium and cause a spectrum of infections (Table 2a). Complex lnfection Risk factors for NTM infections include immunocompro- Mycobacterium auiumcomplex is a common cause of chronic mise, chronic lung disease, and postoperative status. lung infection worldwide. Cavitary lung disease is seen classi- NTM diagnosis is difficult because a positive culture result caliy in White, middle-aged, or older adult men with underly from a nonsterile site without evidence of disease may reflect ing lung disease. Disseminated infection occurs predomi colonization rather than infection. However, when recovered nantly in patients with HIV and CD4 cell counts less than from a sterile site, active infection is likely. Because antibiotic 50/pL. The clinical presentation consists of fever, night sweats, susceptibility among species varies, it is important to identify weight loss, and gastrointestinal symptoms. 38

My cob a cte ri u m tu b e rcu I osis I nfecti o n TABLE 22. Preferred Treatment Regimens for Active Tuberculosis Treatment Phase Regimen Comments lnitial Daily lNH, RlF, PZA, and EMB'for Alternative regimens available at https://www.cdc.gov ltb/topic/treatmenV 56 doses (8 wk)or tbdisease.htm DOT 5 d/wk for 40 doses (8 wk) DOT should be used when medications are administered less than 7 d/wk' Pyridoxine 25-50 mg/d is given to all patients at risk for neuropathyb; 100 mgid for patients with peripheral neuropathy. Continuation INH and RIF 7 d/wk for 126 doses Based on expert opinion, patients with cavitation on the initial chest (18 wk)or radiograph and positive cultures at completion of 2 months of therapy should receive a 7-month (31-wk) continuation phase. DOT 5 d/wk for 90 doses (18 wk) DOT = d irectly observed thera py; EM B = etha m butol; lN H = isoniazid; PZA-- pyrazinam ide; RIF = rifa m pin. "EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs bPregnant women; breastfeeding infants; persons with HIV; patients with diabetes, alcoholism, malnutrition, or chronic kidney disease; patients of advanced age' tb/topic/treatmenvtbdisease.htm. Accessed Ja nua ry 26, 2021 .

"EMB can be discontinued if drug susceptibility studies demonstrate susceptibility to first-line drugs bPregnant women; breastfeeding infants; persons with HIV; patients with diabetes, alcoholism, malnutrition, or chronic kidney disease; patients of advanced age' tb/topic/treatmenvtbdisease.htm. Accessed Ja nua ry 26, 2021 . testing, hepatitis serology) should be performed before KEY POIilT initiating therapy. o In patients with multidrug-resistant tuberculosis It is essential to advise the patient of the possible (resistant to isoniazid and rifampin), experts agree that adverse effect profiles of the various medications (see at least a five-drug regimen should be provided for 5 to Table 21). In several studies, approximately 15% to 25% of 7 months after culture conversion (intensive phase of patients receiving the four-drug regimen experienced some treatment), followed by a four-drug regimen for a total type of adverse effect. Most adverse effects are mild, and treatment duration of 15 to 21 months (continuation therapy may be continued; up to l5o/" are severe enough phase). that therapy must be discontinued temporarily. If a hyper sensitivity reaction is observed, then all four drugs should be discontinued with sequential rechallenging to deter Immune Reconstitution Inflammatory mine the cause. Syndrome in Tuberculosis and HIV Tuberculosis in patients with HIV infection may be compli I(EY POITTS cated by immune reconstitution inflammatory syndrome. . Directly observed therapy is recommended for active Although the general recommendations for treatment are the tuberculosis treatment regimens when medication is same, antiretroviral therapy should be initiated within 2 weeks administered less than 7 days per week. for patients with aCD4 cell count less than 50/pL and by B to o American Thoracic SocietyiCDC guidelines recommend 12 weeks for those with CD4 cell counts of 50/pL or more. An 6 to 9 months of treatment in patients with drug- exception is HlV-positive patients with tuberculous meningi- susceptible active tuberculosis; a four-drug regimen is tis, in whom antiretroviral therapy should not be initiated given daily for 2 months, followed by a continuation during the first 8 weeks of tuberculosis therapy regardless of phase of isoniazid plus rifampin daily, usually for the CD4 cell count to avoid increased morbidity because of 4 months. immune reconstitution inflammatory syndrome. KEY POIf{T Drug-Resistant Tu berculosis o Tuberculosis in patients with HIV infection may be M. tuberculosis resistance to individual drugs arises by spon- complicated by immune reconstitution inflammatory taneous point mutations. Depending on the resistance, the syndrome, and antiretroviral therapy initiation should regimen must be altered. In isoniazid-resistant tuberculosis, be delayed to prevent this occurrence. the recommended regimen of rifampin, ethambutol, and pyrazinamide can be safely administered for 6 months, although adding a later generation fluoroquinolone to the Tumor Necrosis Factor Antagonist regimen is recommended. In those with isoniazid- and and Tuberculosis rifampin-resistant tuberculosis (MDR-TB), experts agree that a Patients being treated with a tumor necrosis factor inhibitor five-drug regimen guided by susceptibility of the isolate (such as infliximab, etanercept, adalimumab, or certolizumab) should be provided for 5 to 7 months, followed by a four drug have been reported to have an increased risk of reactivation regimen for a total treatment duration of 15 to 2l months after tuberculosis and death from disseminated disease. It is recom- conversion (see Table 21). mended that these patients be evaluated for active or latent

testing, hepatitis serology) should be performed before KEY POIilT initiating therapy. o In patients with multidrug-resistant tuberculosis It is essential to advise the patient of the possible (resistant to isoniazid and rifampin), experts agree that adverse effect profiles of the various medications (see at least a five-drug regimen should be provided for 5 to Table 21). In several studies, approximately 15% to 25% of 7 months after culture conversion (intensive phase of patients receiving the four-drug regimen experienced some treatment), followed by a four-drug regimen for a total type of adverse effect. Most adverse effects are mild, and treatment duration of 15 to 21 months (continuation therapy may be continued; up to l5o/" are severe enough phase). that therapy must be discontinued temporarily. If a hyper sensitivity reaction is observed, then all four drugs should be discontinued with sequential rechallenging to deter Immune Reconstitution Inflammatory mine the cause. Syndrome in Tuberculosis and HIV Tuberculosis in patients with HIV infection may be compli I(EY POITTS cated by immune reconstitution inflammatory syndrome. . Directly observed therapy is recommended for active Although the general recommendations for treatment are the tuberculosis treatment regimens when medication is same, antiretroviral therapy should be initiated within 2 weeks administered less than 7 days per week. for patients with aCD4 cell count less than 50/pL and by B to o American Thoracic SocietyiCDC guidelines recommend 12 weeks for those with CD4 cell counts of 50/pL or more. An 6 to 9 months of treatment in patients with drug- exception is HlV-positive patients with tuberculous meningi- susceptible active tuberculosis; a four-drug regimen is tis, in whom antiretroviral therapy should not be initiated given daily for 2 months, followed by a continuation during the first 8 weeks of tuberculosis therapy regardless of phase of isoniazid plus rifampin daily, usually for the CD4 cell count to avoid increased morbidity because of 4 months. immune reconstitution inflammatory syndrome. KEY POIf{T Drug-Resistant Tu berculosis o Tuberculosis in patients with HIV infection may be M. tuberculosis resistance to individual drugs arises by spon- complicated by immune reconstitution inflammatory taneous point mutations. Depending on the resistance, the syndrome, and antiretroviral therapy initiation should regimen must be altered. In isoniazid-resistant tuberculosis, be delayed to prevent this occurrence. the recommended regimen of rifampin, ethambutol, and pyrazinamide can be safely administered for 6 months, although adding a later generation fluoroquinolone to the Tumor Necrosis Factor Antagonist regimen is recommended. In those with isoniazid- and and Tuberculosis rifampin-resistant tuberculosis (MDR-TB), experts agree that a Patients being treated with a tumor necrosis factor inhibitor five-drug regimen guided by susceptibility of the isolate (such as infliximab, etanercept, adalimumab, or certolizumab) should be provided for 5 to 7 months, followed by a four drug have been reported to have an increased risk of reactivation regimen for a total treatment duration of 15 to 2l months after tuberculosis and death from disseminated disease. It is recom- conversion (see Table 21). mended that these patients be evaluated for active or latent 37