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Tuberculosis in solid organ transplant candidates and recipients

Tuberculosis in solid organ transplant candidates and recipients
Literature review current through: Jan 2024.
This topic last updated: Sep 06, 2023.

INTRODUCTION — The incidence of tuberculosis (TB) among solid organ transplant (SOT) recipients is higher compared with the general population but varies by geographic location [1-4]. The diagnosis of TB in SOT recipients presents challenges that may lead to treatment delay. These include atypical clinical presentations, increased likelihood of negative tuberculin skin tests and/or interferon-gamma release assays, and negative sputum smear results despite active disease [5-10]. The treatment of TB in transplant recipients also has its own challenges, which include pharmacokinetic interactions between immunosuppressive and antituberculous medications, allograft-related drug toxicities, and inadequate immune responses to Mycobacterium tuberculosis due to exogenous immunosuppression [5-7,10].

This topic reviews M. tuberculosis infections in SOT recipients. Nontuberculous mycobacterial infections in SOT recipients; bacterial, viral, and fungal infections in lung transplant recipients; and the evaluation, treatment, and prophylaxis of infection in SOT recipients are reviewed separately. (See "Nontuberculous mycobacterial infections in solid organ transplant candidates and recipients" and "Bacterial infections following lung transplantation" and "Prevention of cytomegalovirus infection in lung transplant recipients" and "Clinical manifestations, diagnosis, and treatment of cytomegalovirus infection in lung transplant recipients" and "Fungal infections following lung transplantation" and "Evaluation for infection before solid organ transplantation" and "Infection in the solid organ transplant recipient" and "Prophylaxis of infections in solid organ transplantation".)

EPIDEMIOLOGY

Overview — The prevalence of active TB among transplant recipients in developed countries has ranged from 1.2 to 6.4 percent but has been reported to be as high as 10 to 15 percent in endemic regions [5,6,10,11]. (See "Epidemiology of tuberculosis".)

The incidence of TB in SOT recipients is not well established and varies by geographic location, but the incidence has been shown to be significantly higher among transplant recipients compared with the general population [1-4]. In a prospective study of 4388 SOT recipients at 16 transplant centers in Spain, the incidence of TB was 512 cases per 100,000 patients per year compared with 19 cases per 100,000 inhabitants per year in the general population [1]. Among SOT recipients, lung transplant recipients had the highest incidence of TB (2072 cases per 100,000 patients per year).

Transmission — TB occurs most commonly in transplant recipients as a result of reactivation of latent infection in the recipient but also may arise from unrecognized infection in the allograft or acquisition of new infection after transplantation [5,6,12,13]. There are several reports of TB transmission from the donor allograft to the recipient [6,12,14-18], especially when the donor country of origin is highly endemic for TB [17,19]. A report by the US Organ Procurement Transplantation Network (OPTN) ad hoc Disease Transmission Advisory Committee (DTAC) found proven or probable TB transmission from 9 donors to 6 lung and 5 non-lung recipients over a 10-year period [17].

Timing following transplantation — In a prospective study of TB in SOT recipients, TB occurred a median of 183 days after transplantation (range 28 to 499 days), with 95 percent of cases occurring within the first year [1]. Among lung transplant recipients, the median time to onset was 3.5 months following transplantation compared with 11.5 months among renal transplant recipients [1]. Donor-derived TB typically occurs earlier than reactivation of latent TB that originated in the recipient. In a retrospective review of over 2000 cases of TB in SOT recipients, the median time to presentation was 22 months overall [4]. Among donor-derived cases of TB, the time to clinical presentation appears to be shorter, with a median of 2.7 months [16], and, in the OPTN DTAC report, the median time to TB diagnosis in proven or probable transmission cases was 104 days post-transplant [17]. Similar findings have been reported in another retrospective review [20].

CLINICAL MANIFESTATIONS

Presenting manifestations — About one-third to one half of all cases of active TB after transplant are disseminated or occur at extrapulmonary sites, a much higher rate than that seen in immunocompetent hosts [5,21]. Lung transplant recipients are most likely to develop pulmonary manifestations of TB, although disseminated disease also occurs in a substantial proportion of patients [5]. Furthermore, TB may have an atypical presentation in this population (eg, pyomyositis, cutaneous ulcers or abscess, tenosynovitis).

Fever occurred in 91 percent of SOT recipients with disseminated TB and 64 percent of those with localized TB; night sweats and weight loss were also common [5].

Radiographic findings — Only a small minority of transplant patients has classic cavitary changes on chest radiograph. Radiographic findings of pulmonary TB in SOT recipients have included a focal infiltrate (40 percent), a miliary pattern (22 percent), nodules (15 percent), pleural effusions (13 percent), diffuse interstitial infiltrates (5 percent), and cavities (4 percent) [5]. (See "Pulmonary tuberculosis: Clinical manifestations and complications" and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

DIAGNOSIS — The diagnosis of active TB in transplant recipients requires a high index of suspicion and often requires an invasive procedure, such as bronchoscopy with bronchoalveolar lavage or lung biopsy. TB should be considered in all transplant recipients with unexplained fevers, night sweats, and weight loss and in all lung transplant recipients with evidence of pulmonary infection. Staining and culture for acid-fast bacilli should be performed on all induced sputum and bronchoscopy specimens in such patients. Nucleic acid amplification methods can increase the rapidity of diagnosis when the suspicion for TB is high. In addition, mycobacterial infections should be considered in transplant recipients with atypical skin lesions or soft tissue infections. Skin biopsy specimens and/or abscess fluid should be sent for acid-fast bacilli staining and culture and histopathology. It should be noted that neither tuberculin skin testing nor interferon-gamma release assays distinguish between active and latent TB. (See "Diagnosis of pulmonary tuberculosis in adults".)

MANAGEMENT OF ACTIVE TUBERCULOSIS — The recommendations in the following section reflect the 2012 TBNET consensus statement [22], the 2019 guidelines of the American Society of Transplantation (AST) [10], and the 2014 guidelines of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) [23].

Recommendations for the treatment of active TB in transplant recipients are based largely on randomized trials in immunocompetent hosts [24]. Data regarding the safety and efficacy of TB therapy in SOT recipients come from retrospective studies, case reports, and case series [5,25-31]. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

The AST, ESCMID, and TBNET have all recommended that the approach to the treatment of TB in SOT recipients be similar to immunocompetent hosts [10,11]. However, the following important issues specific to SOT recipients should be noted:

The AST states that a rifamycin-containing regimen is strongly preferred for both severe and localized nonsevere TB due to the potent sterilizing activity of such regimens and the importance of preventing the emergence of resistance [10].

TBNET and ESCMID suggest a non-rifamycin-based regimen in cases of localized (eg, pulmonary) nonsevere TB when there is no suspicion or evidence of isoniazid (INH) resistance [11,23]. In patients not receiving a rifamycin, treatment options include a three-drug regimen of INH plus ethambutol plus either pyrazinamide or levofloxacin for 2 months, followed by a two-drug regimen of INH plus ethambutol or pyrazinamide for 12 to 18 months. In those receiving a three-drug regimen for the entirety, the duration of treatment can be shortened to 12 months.

Experts agree that rifamycins are indicated in patients with severe (eg, cavitary or multilobar disease) or disseminated TB or when there is suspicion or documentation of INH resistance [10,11].

Rifampin should be used with caution due to significant interactions between this class of drug and the calcineurin inhibitors and rapamycin (sirolimus). The rifamycins (especially rifampin) reduce serum concentrations of tacrolimus, cyclosporine, rapamycin (sirolimus), and everolimus via induction of the cytochrome p450 isoenzyme CYP3A4, and the combination of a rifamycin with these drugs has been associated with the development of rejection [10,11,25,32]. Rifamycins also reduce levels of glucocorticoids, although this has been less well characterized [11].

If rifampin is used, the dose of the calcineurin inhibitor or rapamycin should be increased approximately three- to fivefold, and serum concentrations should be monitored [11]. CYP3A4 induction by rifampin takes several days to occur, usually peaks within a week, and lasts for days to weeks [33,34]. Rifabutin is an attractive alternative to rifampin because it has similar activity against M. tuberculosis but is a weaker inducer of cytochrome p450 [10,11,35-37]. While there is less experience with rifabutin in the treatment of TB in transplant recipients, it appears effective in HIV-infected individuals [10,11]. (See "Rifamycins (rifampin, rifabutin, rifapentine)".)

Patients receiving a rifamycin-containing regimen should be treated for a minimum of six months. However, duration should be extended in patients with severe disseminated disease, cavitary disease with sputum that remains culture positive after two months of treatment, bone and/or joint disease, or central nervous system disease. Some experts recommend that treatment should be continued for at least nine months in all SOT recipients, since a shorter duration may be associated with increased mortality in this population [25].

Although streptomycin is often used as part of the initial treatment regimen in nontransplant patients with a contraindication to the rifamycins, this agent is generally avoided in SOT recipients because of the risk of nephrotoxicity [11].

The TB treatment regimen will depend on local resistance patterns and epidemiologic and susceptibility data from the individual patient's isolate. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection" and "Treatment of drug-resistant pulmonary tuberculosis in adults".)

Caution is advised against the overzealous reduction in immunosuppression while treating post-transplant TB given the challenge of immune reconstitution inflammatory syndrome (IRIS). Antituberculous therapy reverses the immunosuppressive effects associated with TB infection, and IRIS may manifest with a paradoxical worsening of pulmonary infiltrates, fever, pleural or pericardial effusion, or lymphadenopathy [38]. In a multicenter prospective study of TB in transplant recipients, IRIS developed in 9 of 64 patients (14.1 percent) at a median of 47 days after initiation of antituberculous medications [38]. The presence of two or more of the following factors was associated with increased risk of IRIS: liver transplantation, previous cytomegalovirus infection, and use of rifampin. There was no association noted between reduction of immunosuppression and IRIS, however, as very few patients had dose reductions. IRIS associated with mycobacterial infections is discussed in greater detail separately. (See "Immune reconstitution inflammatory syndrome".)

PROGNOSIS — The mortality of TB is higher among SOT recipients compared with immunocompetent individuals. In a literature review published in 1998 of TB in SOT recipients, 146 of 499 patients (29 percent) died [5]. Predictors of mortality included disseminated disease, prior rejection, and receipt of OKT3 or anti-T cell antibodies. However, in another study, disseminated disease was not associated with increased mortality [25].

Newer studies demonstrate decreasing mortality rates due to TB in SOT. In a prospective study of TB among SOT recipients, crude mortality was 19 percent, but mortality attributable to TB was only 10 percent [1]. In a multicenter study with 64 cases of TB in two subsequent SOT cohorts, the later cohort (2008 to 2011) had a mortality of 10 percent as well. Further, the increased risk of rejection caused by the interaction between the rifamycins and the calcineurin inhibitors was previously thought to contribute to the morbidity of TB in SOT recipients [6]. However, two multicenter studies in which the majority of patients received a rifampin-based regimen did not show a difference in rejection rates or mortality [39,40].

As stated above, if immunosuppression is reduced upon starting TB treatment, there is also the possibility of immune reconstitution inflammatory syndrome, as is seen in HIV patients who receive antiretroviral therapy along with antituberculous medicines [38]. (See "Immune reconstitution inflammatory syndrome".)

PREVENTION

Screening — There are two available testing methods that can be used to screen for latent TB, the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA); both tests have lower sensitivity in immunocompromised hosts than in immunocompetent hosts [41,42]. Neither the TST nor IGRA detects the mycobacterium directly; both are dependent on the host's cellular immune response to the pathogen. Just as TST can be negative due to cutaneous anergy, IGRA results are reported as indeterminate when there is an inadequate interferon-gamma response to the positive control, which can be the result of a diminished cellular immune response or technical issues in collecting the sample [43].

Our approach to screening for latent TB depends in part upon the patient's type and degree of organ dysfunction (algorithm 1):

For SOT candidates who do not have end-stage kidney disease or advanced liver disease, we use either the TST or the IGRA.

If the TST is performed and is negative, it should be repeated two weeks later if feasible in order to detect the booster effect [10,11]. Induration ≥5 mm is considered to be a positive result. In patients from a country with a high prevalence of TB or in those who have other TB risk factors, we favor performing the IGRA in addition to the TST if the TST is negative.

For most patients with a history of a positive TST, it is not necessary to perform an IGRA because a positive TST provides proof of latent TB. Patients who have received the Bacille Calmette-Guérin (BCG) vaccine after the first year of life are an exception because BCG vaccine receipt can cause a false-positive TST, and such patients should be evaluated with the IGRA. If either the IGRA or TST has been positive in an adult transplant candidate with no history of receiving BCG after infancy, the patient should be considered to have latent TB.

For SOT candidates with end-stage kidney disease or advanced liver disease, we use the IGRA to screen for latent TB. We do not do a TST because it appears to have lower sensitivity than the IGRA in such patients [8,44-47]. For those with a negative IGRA, we consider the risk of latent TB and treat those at high risk [48]. (See 'Treatment of latent tuberculosis' below.)

In a meta-analysis of studies of patients with end-stage kidney disease in countries with a low prevalence of TB, a positive IGRA result was associated more strongly with radiologic evidence of past TB (relative odds ratio [ROR] 4.29, 95% CI 1.83-10.3) and contact with active TB (ROR 3.36, 95% CI 1.61-7.01) than a positive TST result [47]. A study of 71 South Korean patients who were TST negative and IGRA positive prior to kidney transplant suggested that the IGRA may have a higher predictive value for progression to active TB after transplant [44]. In a Spanish study of 95 patients awaiting liver transplant, the rate of positive TST decreased with more advanced stages of liver disease, whereas IGRA positivity showed no association with stage of liver disease, suggesting that IGRA may be superior to TST in patients with advanced liver disease [45].

If the IGRA gives an indeterminate result, it should be repeated to make sure there are no technical or laboratory flaws. If the repeat result is also indeterminate, then the clinician cannot rely on the IGRA for clinical decision-making, except to assume that the patient is probably not able to mount an interferon-gamma response to mitogen [49]. For those with two indeterminate IGRAs, the decision regarding the need for treatment of latent TB will need to be made on a case-by-case basis according to the individual's risk-benefit ratio, with consideration of signs of prior infection (eg, granulomas on chest imaging), prior contact with people with known disease, other history of probable exposures, and risk of drug toxicities [48]. (See 'Treatment of latent tuberculosis' below.)

We prefer the IGRA in patients who received BCG since its results are not affected by receipt of BCG. In contrast, BCG may cause the TST to be positive, especially in individuals who received it upon starting primary school (as opposed to during infancy).

In patients with evidence of latent TB by TST and/or IGRA, a thorough evaluation for evidence of active TB is indicated. If the sputum is positive for TB by staining or culture, transplantation should ideally be delayed until the patient has been treated. While it is preferable for the treatment course to be completed before transplantation, we generally take the urgency of the underlying need for transplantation and the severity of TB infection into account when determining the timing of transplantation. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

Screening for latent TB is discussed in greater detail separately. (See "Use of interferon-gamma release assays for diagnosis of tuberculosis infection (tuberculosis screening) in adults".)

Treatment of latent tuberculosis

Whom to treat — Transplant candidates and recipients should be treated for latent TB when there is no evidence of active TB and any of the following criteria are met [10,11]:

Initial or boosted TST with induration ≥5 mm or a positive IGRA

History of untreated latent TB

Receipt of an organ from a donor known to have untreated latent TB

Other patients for whom we consider treatment for latent TB on an individual basis include:

Transplant candidates or recipients with recent close and prolonged contact with an individual with active TB, even with negative TST or IGRA, given the high risk of primary infection [10]

Patients who have an indeterminate IGRA on repeat testing for an initial indeterminate result who are at high risk for latent TB (see 'Screening' above)

Transplant candidates with chest radiographic evidence suggestive of previous TB (apical fibronodular lesions, calcified solitary nodule, calcified lymph nodes, or pleural thickening) who have not been treated should undergo aggressive evaluation, including a thorough epidemiologic history, to determine whether the abnormalities are most likely to represent TB or another granulomatous infection (eg, histoplasmosis). In regions in which endemic mycoses are common and TB is uncommon (eg, parts of the United States), such an evaluation is important to ensure that individuals are not treated unnecessarily for latent TB.

Regimen selection — For treatment of latent TB, we follow national guidelines [10,11,50] while taking into account issues of drug interactions and organ failure encountered in transplant patients.

When the transplant is unlikely to occur within the following 4 to 6 months, we typically prescribe rifampin for 4 months [51]. Other options pretransplant are isoniazid plus rifapentine for 12 weeks, or isoniazid plus rifampin for 3 months. The combination of isoniazid and rifapentine has been studied in healthy individuals over 12 years of age as weekly directly observed therapy [52-57]. There are now data for self-administration, and the combination has been used in transplant candidates as well [53,54,58].

All of these regimens are limited by the drug-drug interactions between rifamycins and both calcineurin inhibitors and rapamycin (sirolimus); rifamycin-containing regimens can be used prior to transplant but are not recommended after transplant.

If the treatment course will start, or likely continue, after transplant we typically use oral isoniazid 5 mg/kg (maximum dose 300 mg) daily for adults and 10 to 15 mg/kg (maximum dose 300 mg) daily for children for a duration of nine months; oral pyridoxine 25 to 50 mg daily should also be administered (table 1) [10,11,50]. An alternative regimen is isoniazid with pyridoxine for 6 months. The risk of severe hepatotoxicity from isoniazid is significant even in immunocompetent hosts [59]. In SOT candidates and recipients receiving isoniazid, serum aspartate aminotransferase, alanine aminotransferase (ALT), and bilirubin should be monitored at baseline and at least monthly thereafter [11]; some experts favor testing for hepatotoxicity by monitoring ALT levels every two weeks for six weeks, then monthly thereafter [10].

Timing of treatment — When possible, we treat transplant candidates with latent TB prior to transplantation, although it is also acceptable to treat following transplantation [10,11]. Patients may proceed to transplant before the full course of therapy for latent TB has been given. In these cases, therapy is typically continued post-transplant, but the regimen sometimes needs to be modified to minimize toxicities and drug-drug interactions.

For liver transplant candidates, treating prior to transplantation is especially challenging because of the potential hepatoxicity of isoniazid. Treatment prior to transplantation can be attempted with very close monitoring of liver function tests; rifampin for four months is an alternate option that can be used when feasible. However, in such cases, it may be safer to begin therapy after transplantation once liver function has normalized. (See 'Epidemiology' above and 'Clinical manifestations' above and "Infectious complications in liver transplantation", section on 'Tuberculosis prevention'.)

For most patients who have received an organ from a donor known to have untreated latent TB, we treat the recipient post-transplant (as well as the donor, if indicated). For patients with living donors, the donor can be treated for latent TB prior to transplantation if the transplant is not urgent. If the donor is fully treated prior to transplantation, it is not necessary to treat the recipient. For patients with deceased donors, untreated latent TB can be difficult to diagnose based on history from family members alone. In a study of 105 deceased donors from Germany, detection of antigen-specific cellular immunity to TB was compared using two different IGRA methods and flow cytometry [60]. Despite the variability in the assay results and higher rates of indeterminate results compared with living donors, there may be a role for positive IGRA results to guide decisions about chemoprophylaxis, which deserves further study.

Practices for the management of latent TB among transplant candidates and recipients vary in different countries, largely due to differences in the regional prevalence of TB. Treatment of latent TB in general is discussed in greater detail separately. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection".)

Efficacy — Randomized trials have proven the efficacy of treating latent TB in immunocompetent individuals, but only case reports, case series, and observational studies have suggested benefit in SOT candidates and recipients [5]. In a review of six randomized controlled trials in TB endemic areas, 20 of 641 transplant patients who received latent TB treatment developed active TB, compared with 62 or 544 who did not (relative risk = 0.25, p = 0.00001), with an absolute risk reduction of 0.08 [61]. The increased risk of reactivation and severe disease among SOT recipients argues for initiation of treatment for latent TB, particularly in regions in which TB is endemic. In most cases, the benefit of treatment of latent TB outweighs the risks in the transplant setting. The annual risk for active TB in immunocompromised transplant recipients with a positive TST may be as high as 7.4 percent without treatment [62]. In a European study of immunocompromised patients, the overall incidence of active TB was low, but no cases occurred in patients who received treatment for latent TB [63]. Moreover, studies have shown a low risk of isoniazid hepatotoxicity in renal transplant recipients without serious liver disease and in patients with compensated liver disease awaiting liver transplantation who have had close follow-up and monitoring [64-66].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diagnosis and treatment of tuberculosis" and "Society guideline links: Infections in solid organ transplant recipients".)

SUMMARY AND RECOMMENDATIONS

Active tuberculosis

The incidence of tuberculosis (TB) in solid organ transplant (SOT) recipients is not well established and varies by geographic location. The prevalence of active TB among transplant recipients in developed countries has ranged from 1.2 to 6.4 percent but has been reported to be as high as 10 to 15 percent in endemic regions. (See 'Epidemiology' above.)

One-third to one half of cases of TB after transplant are disseminated or extrapulmonary. Lung transplant recipients are most likely to develop pulmonary manifestations of TB. (See 'Clinical manifestations' above.)

TB should be considered in all transplant recipients with evidence of pulmonary or cutaneous lesions. Depending on the site(s) of involvement, appropriate clinical specimens should be sent (eg, staining and culture for acid-fast bacilli [AFB] on bronchoalveolar lavage fluid or abscess fluid; AFB staining and culture and histopathology on biopsy specimens). (See 'Diagnosis' above.)

In SOT patients with localized nonsevere TB without suspicion or evidence of isoniazid (INH) resistance, we suggest using the rifamycin-containing regimens used in immunocompetent hosts (Grade 2C). However, due to drug interactions, some advocate the avoidance of rifamycins in this scenario. When rifampin is not used, a longer than usual duration of treatment is required. (See 'Management of active tuberculosis' above.)

In patients with severe or disseminated TB or when there is suspicion or evidence of INH resistance, we suggest a regimen that includes a rifamycin; such a regimen is identical to that recommended for immunocompetent hosts (Grade 2C). (See 'Management of active tuberculosis' above.)

The rifamycins, particularly rifampin, reduce serum concentrations of tacrolimus, cyclosporine, rapamycin (sirolimus), and everolimus via induction of the cytochrome p450 isoenzyme CYP3A4. The combination of rifampin with members of this class of drugs can lead to the development of rejection unless dose adjustments and therapeutic drug monitoring are performed carefully. (See 'Management of active tuberculosis' above.)

Rifabutin is an attractive alternative to rifampin because it is a weaker inducer of cytochrome p450. However, there is less experience with rifabutin in the treatment of TB. Treatment should be continued for at least six months, and some experts recommend routine extension to nine months in transplant recipients. (See 'Management of active tuberculosis' above.)

The TB treatment regimen will depend on local resistance patterns and epidemiologic and susceptibility data from the individual patient's isolate. (See 'Management of active tuberculosis' above.)

Latent tuberculosis

Screening for latent TB should be performed in all SOT candidates. There are two available tests that can be used to screen for latent TB, the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA). Both tests have lower sensitivity in immunocompromised hosts than in immunocompetent hosts. Our approach to screening for latent TB depends in part upon the patient's type and degree of organ dysfunction and is discussed in detail above (algorithm 1). (See 'Screening' above.)

We recommend that SOT candidates and recipients be treated for latent TB if they meet any of the following criteria (Grade 1B) (see 'Treatment of latent tuberculosis' above):

TST (initial or boosted) with induration ≥5 mm and/or a positive IGRA

History of untreated latent TB

History of contact with an individual with active TB

Receipt of an organ from a donor known to be TST positive if the donor has no history of treatment for latent TB

We suggest that SOT candidates who are at high risk for primary TB (eg, recent history of contact with an individual with active TB) be treated for latent TB even if screening tests are negative (Grade 2C). (See 'Treatment of latent tuberculosis' above.)

For those with repeated (ie, two) indeterminate IGRAs, the decision regarding the need for treatment of latent TB will need to be made on a case-by-case basis according to the individual's risk-benefit ratio, with consideration of signs of prior infection (eg, granulomas on chest imaging), prior contact with people with known disease, other history of probable exposures, and risk of drug toxicities. (See 'Treatment of latent tuberculosis' above.)

For the treatment of latent TB for most transplant candidates we use rifampin for 4 months, weekly isoniazid plus rifapentine for 12 weeks, or isoniazid plus rifampin for 3 months; rifamycin-containing regimens can be used prior to transplant but are not recommended after transplant due to drug-drug interactions.

After transplant or when rifamycins cannot be used pretransplant, we use oral isoniazid 5 mg/kg (maximum dose 300 mg) daily for adults and 10 to 15 mg/kg (maximum dose 300 mg) daily for children for a duration of nine months; oral pyridoxine 25 to 50 mg daily should also be administered (table 1). Alternative regimens for latent TB treatment include isoniazid for 6 months. (See 'Treatment of latent tuberculosis' above.)

In SOT candidates and recipients receiving isoniazid, serum aspartate aminotransferase, alanine aminotransferase (ALT), and bilirubin should be monitored at baseline and at least monthly thereafter; some experts favor testing for hepatotoxicity by monitoring ALT levels every two weeks for six weeks, then monthly thereafter. (See 'Treatment of latent tuberculosis' above.)

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Topic 1407 Version 26.0

References

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