Tuberculosis in solid organ transplant candidates and recipients

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 TB 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".)

TERMINOLOGY — 

TB terminology is inconsistent in the literature. Relevant terms are defined in the table (table 1).

EPIDEMIOLOGY

Overview — The prevalence of TB disease among transplant recipients in resource-abundant settings 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 is higher among SOT recipients compared with the general population, and varies by geographic location [1-4]:

●In a study including 4388 SOT recipients at 16 transplant centers in Spain between 2003 and 2006, the incidence of TB was 512 cases per 100,000 patients per year compared with 19 cases per 100,000 people 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).

●In a study using California TB Registry Data from 2010 to 2020, the incidence of TB disease in SOT recipients was 56 per 100,000 person-years, compared with an incident of 5.4 cases per 100,000 person-years in the general population [12].

Transmission — TB disease occurs most commonly in transplant recipients as a result of reactivation of TB infection in the recipient; it may also arise from unrecognized TB infection in the allograft or acquisition of new infection after transplantation [5,6,13,14]. There are several reports of TB transmission from the donor allograft to the recipient [6,13,15-20], especially when the donor country of origin is highly endemic for TB [18,21]. A report by the US Organ Procurement Transplantation Network (OPTN) ad hoc Disease Transmission Advisory Committee (DTAC) found proven or probable TB transmission from nine donors to six lung and five non-lung recipients over a 10-year period [18].

In addition, outbreaks of donor-derived TB in bone allograft tissue recipients have occurred. In one outbreak from a single tissue donor with unrecognized TB in 2021, 77 percent of 113 product recipients developed microbiologic or radiographic evidence of TB disease, with three deaths attributed to TB [22]. In another outbreak in 2023 from a deceased donor, 5 of 36 recipients developed laboratory-confirmed TB disease with at least two TB-related deaths [23].

Timing following transplantation — In general, TB disease occurs earlier among lung transplant recipients than among renal transplant recipients. In addition, donor-derived TB disease typically occurs earlier than the reactivation of TB infection that originated in the recipient:

●In a Spanish prospective study of TB in SOT recipients cited above, 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].

●In the California study above, the median time from transplant to diagnosis of TB disease was 1.2 years, with the shortest time among lung transplant recipients (0.2 years) and longest in kidney transplantation (2.4 years) [12].

●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 [17], and, in the OPTN DTAC report, the median time to TB diagnosis in proven or probable transmission cases was 104 days post-transplant [18]. Similar findings were reported in another retrospective review [24].

TUBERCULOSIS DISEASE

Clinical manifestations

Presenting manifestations — About one-third to one half of all cases of tuberculosis (TB) disease after transplant are disseminated or occur at extrapulmonary sites, a much higher rate than that seen in immunocompetent hosts [5,25]. Lung transplant recipients are most likely to develop pulmonary manifestations of TB, although disseminated disease also occurs in a substantial proportion of patients [5]. The most common extrapulmonary TB sites among SOT recipients are pleura, cervical lymph nodes, and bone [12], but 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 disease in adults: Clinical manifestations and complications" and "Clinical manifestations, diagnosis, and treatment of miliary tuberculosis".)

Diagnosis — The diagnosis of TB disease 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.

Neither tuberculin skin testing nor interferon-gamma release assays distinguish between TB disease and TB infection. (See "Diagnosis of pulmonary tuberculosis in adults".)

Management — The recommendations in the following section reflect the 2012 Tuberculosis Network European Trials Group (TBNET) consensus statement [26], 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) [27].

Recommendations for the treatment of TB disease in transplant recipients are based largely on randomized trials in immunocompetent hosts [28]. Data regarding the safety and efficacy of TB therapy in SOT recipients come from retrospective studies, case reports, and case series [5,29-35]. (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 [11,27]. In patients not receiving a rifamycin, treatment options include a three-drug regimen of INH plus ethambutol plus either pyrazinamide or levofloxacin for two 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 [10,11,29,36]. 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 [37,38]. Rifabutin is an attractive alternative to rifampin because it has similar activity against M. tuberculosis but is a weaker inducer of cytochrome p450 [10,11,39-41]. Patients receiving a rifamycin in this setting should also be monitored for rare hematologic or hepatic toxicity and for rifabutin-associated optic neuritis. While there is less experience with rifabutin in the treatment of TB in transplant recipients, it appears effective in individuals with HIV [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 TB disease, or central nervous system TB 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 [29].

●Aminoglycosides (streptomycin, amikacin, kanamycin) or capreomycin generally are 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 [42]. 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 [42]. 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, very few patients had dose reductions. IRIS associated with mycobacterial infections is discussed in greater detail separately. (See "Overview of immune reconstitution inflammatory syndromes".)

Prognosis — TB disease impacts graft survival and patient survival. One study found a 2.8 times higher hazard of death in SOT recipients with posttransplant TB than those without TB; in addition, among kidney transplant recipients with TB, the hazard of graft failure was 3.4 times higher than in those without TB [12].

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 [29].

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 subsequent multicenter studies in which the majority of patients received a rifampin-based regimen did not show a difference in rejection rates or mortality [43,44].

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 [42]. (See "Overview of immune reconstitution inflammatory syndromes".)

TUBERCULOSIS INFECTION

Screening — There are two available testing methods that can be used to screen for tuberculosis (TB) infection, the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA); both tests have lower sensitivity in immunocompromised hosts than in immunocompetent hosts [45,46]. 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 response capacity to a non-immune (mitogen) stimulus or technical issues in collecting and processing the sample [47].

Our approach to screening for TB infection 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 TB infection. 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 TB infection.

●For SOT candidates with end-stage kidney disease or advanced liver disease, we use the IGRA to screen for TB infection. We do not do a TST because it appears to have lower sensitivity than the IGRA in such patients [8,48-51]. For those with a negative IGRA, we consider the risk of TB infection and treat those at high risk [52]. (See 'Treatment' 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 TB disease (ROR 3.36, 95% CI 1.61-7.01) than a positive TST result [51]. 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 TB disease after transplant [48]. 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 [49].

●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 [53]. For those with two indeterminate IGRAs, the decision regarding the need for treatment of TB infection 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 (such as residence in a TB-endemic region), and risk of drug toxicities [52]. (See 'Treatment' 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 TB infection by TST and/or IGRA, a thorough evaluation for evidence of TB disease 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 and response to therapy into account when determining the timing of transplantation. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

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

Treatment

Whom to treat — Transplant candidates and recipients should be treated for TB infection when there is no evidence of TB disease 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 TB infection

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

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

●Transplant candidates or recipients with recent close and prolonged contact with an individual with TB disease, 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 TB infection (see 'Screening' above)

Transplant candidates with chest radiographic evidence suggestive of previous TB (apical fibronodular lesions, calcified solitary nodules, calcified lymph nodes, or pleural thickening with calcification) 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 TB infection.

Regimen selection — For treatment of TB infection, we follow national guidelines [10,11,54] while taking into account issues of drug interactions and organ failure encountered in transplant patients.

●Treatment prior to transplant – If a transplant is unlikely to occur within four to six months, we typically prescribe rifampin for four months [55].

Other options are isoniazid (INH) plus rifapentine for 12 weeks (3HP), or INH plus rifampin for three months (3HR). The combination of INH and rifapentine was originally studied in healthy individuals over 12 years of age as weekly directly observed therapy [56-61]. There are now data for self-administration, and the combination has been used in transplant candidates as well, albeit with limited data on long-term post-transplant follow-up for efficacy [57,58,62,63].

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.

●Treatment after transplant – If the treatment course will start, or likely continue, after transplant (in the absence of suspected drug resistance) we typically use oral INH 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 2) [10,11,54].

●An alternative regimen is INH with pyridoxine for six months (although protection is likely as good as nine months) [54]. The risk of severe hepatotoxicity from INH is significant even in immunocompetent hosts [64].

●In SOT candidates and recipients receiving INH, 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].

●Multidrug-resistant TB exposure – For contacts exposed to multidrug- or rifampin-resistant TB, the World Health Organization (WHO) favors use of daily levofloxacin for six months [65]; however, there are no data on the use of this drug for TB prevention in organ transplant recipients. A study of levofloxacin versus INH for TB infection in liver transplant recipients was stopped due to a high incidence of tenosynovitis in the levofloxacin arm [66].

●Issues related to the treatment of drug-resistant TB infection are discussed further separately [67-69]. (See "Treatment of tuberculosis infection (latent tuberculosis) in nonpregnant adults without HIV infection", section on 'Drug-resistant tuberculosis infection (TBI)'.)

Timing of treatment — When possible, we treat transplant candidates with TB infection 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 TB infection 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 INH. 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 TB infection, we treat the recipient post-transplant (as well as the donor, if indicated). For patients with living donors, the donor can be treated for TB infection 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 TB infection 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 [70]. 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 TB infection among transplant candidates and recipients vary in different countries, largely due to differences in the regional prevalence of TB. Treatment of TB infection 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 TB infection 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 treatment for TB infection developed TB disease, compared with 62 or 544 who did not (relative risk [RR] 0.25), with an absolute risk reduction of 0.08 [71]. The increased risk of reactivation and severe disease among SOT recipients argues for initiation of treatment for TB infection, particularly in regions in which TB is endemic. In most cases, the benefit of treatment of TB infection outweighs the risks in the transplant setting. The annual risk for TB disease in immunocompromised transplant recipients with a positive TST may be as high as 7.4 percent without treatment [72]. In a European study of immunocompromised patients, the overall incidence of TB disease was low, but no cases occurred in patients who received treatment for TB infection [73]. Moreover, studies have shown a low risk of INH 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 [74-76].

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

●Tuberculosis (TB) disease

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

•Diagnosis – TB should be considered in transplant recipients with evidence of pulmonary or cutaneous lesions. Diagnostic specimens should be guided by the site(s) of involvement (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.)

•Management (see 'Management' above)

-In solid organ transplant (SOT) recipients with localized nonsevere TB without suspicion or evidence of isoniazid (INH) resistance, we suggest using a rifamycin-based regimen (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.

-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).

-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.

●TB infection screening – Screening for TB infection should be performed in all SOT candidates (algorithm 1). Tools include the tuberculin skin test (TST) and the interferon-gamma release assay (IGRA); both have diminished sensitivity in immunocompromised hosts. (See 'Screening' above.)

●TB infection treatment

•Whom to treat – We recommend that SOT candidates and recipients be treated for TB infection if they meet any of the following criteria (Grade 1B) (see 'Whom to treat' above):

-TST with induration ≥5 mm and/or a positive IGRA

-History of untreated TB infection

-History of contact with an individual with TB disease

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

For SOT candidates who are at high risk for primary TB (eg, recent history of contact with an individual with TB disease), we suggest treatment for TB infection even if screening tests are negative (Grade 2C).

•Regimen selection (see 'Regimen selection' above)

-Prior to transplant – For the treatment of TB infection prior to transplant we typically use rifampin for four months (4R); other options include INH plus rifapentine for 12 weeks (3HP) or INH plus rifampin for three months (3HR). Rifamycin-containing regimens are not recommended after transplant due to drug-drug interactions.

-After transplant – For treatment of TB infection after transplant, or if rifamycins cannot be used prior to transplant, we use oral INH for nine months (table 2).