HomeRecipients of solid-organ transplantation have a substantially elevated risk of TB that can range between 4 and 30 times that of the general population.56 This is a result of the potent impact of anti-rejection medications on host T-cell function and cell-mediated immune response.57 Most commonly, TB in this population represents reactivation of latent infection in the recipient. However, transmission of unrecognized infection in the allograft (donor-derived infection) and acquisition of new infection post-transplantation can also occur.
TB in transplant recipients is frequently atypical in its clinical presentation.58–60 Disseminated disease is present in up to 15-30% at TB diagnosis and cavitary disease is less frequent in this population.58,61 TB often occurs within the first year following organ transplantation, reflecting both reactivation of previous infection and the period of the most intense immune suppression. Donor-derived TB (ie, TB arising from the transplanted organ) typically presents within three months of organ transplantation.
TB treatment is more difficult and outcomes are worse in solid-organ transplant recipients compared to other populations.58,62 Overlapping drug toxicity and drug-drug interactions lead to adverse events in nearly one-third of transplant recipients receiving TB therapy.58,63 Graft dysfunction and organ rejection occur more frequently in transplant recipients with TB compared to those without TB; this is related in part to drug-drug interactions reducing the serum concentrations of immune-suppression therapies. Mortality from TB is higher in transplant recipients, with rates up to 20% in modern cohort studies.58,63,64
Drug-induced liver injury occurs frequently in transplant recipients, with rates especially high in liver recipients. INH can still be included as part of a first-line regimen, provided liver enzymes and liver function are closely monitored. Pyrazinamide (PZA) should be avoided in liver transplant recipients.59,63,65
Despite potential for drug-interactions, most experts recommend rifamycin-based for treatment of TB in transplant recipients.60,65–67 However, interactions between TB and immunosuppressive agents necessitates close collaboration with transplant physicians and pharmacists.60,66
Rifabutin, which exerts less potent drug-interactions than rifampin, is the preferred rifamycin for treatment of active TB in this population.68,69 The efficacy of rifabutin against TB has been demonstrated in clinical trials (albeit in non-transplant recipients) and is considered comparable to rifampin20,70–73 (see Chapter 5: Treatment of Tuberculosis Disease). Importantly, rifabutin use appears to lessen the risk of graft rejection in transplant recipients.70 Regular therapeutic drug monitoring of anti-rejection medications is recommended while on a rifamycin-containing TB treatment.
Dose reduction of immune suppression in transplant recipients is not needed to achieve cure of TB when using rifamycin-based TB treatment regimens. Furthermore, aggressive dose reduction of anti-rejection medications could potentially lead to an inflammatory immune-reconstitution syndrome that in some cases can be severe or life-threatening.74
Mold-active azoles (eg, voriconazole, posaconazole) are used as prophylaxis against fungal infection in some transplant recipients. Serum concentrations of these agents are substantially reduced by rifamycins. There is also a bi-directional interaction with rifabutin, which risks potential rifabutin toxicity. In some centers, azole prophylaxis is avoided.
Therapeutic drug monitoring of anti-TB drugs is also commonly performed in recipients of solid-organ transplants, due to the potential for altered pharmacokinetics in these complicated populations.
TB drugs for solid-organ transplant recipients should be administered daily throughout the treatment course and these patients should be provided with directly observed therapy (DOT) and/or close supportive care. Treatment extension to nine months is endorsed for this population but direct evidence to support this is lacking.67,75 Many experts recommend longer treatment courses in transplant recipients, reasoning that, as in untreated HIV infection, where there is also persistent cell-mediated immune dysfunction, treatment extension has been demonstrated in controlled trials to reduce relapse risk.16
Recommendations
-
We strongly recommend rifamycin-based therapy for optimal treatment of TB in solid-organ transplant recipients (good evidence).
-
We conditionally recommend rifabutin over rifampin to reduce the risk of potentially severe drug interactions with anti-rejection medications (poor evidence).
-
We conditionally recommend, given the potentially severe risk of drug-drug interactions, regular therapeutic drug monitoring of anti-rejection medications (poor evidence).
-
We conditionally recommend treatment extension to nine months for solid-organ transplant recipients (poor evidence).
Switch To: Français