Rifabutin for treating tuberculosis in solid organ transplant recipients: A retrospective observational study and literature review

Abstract

Background The treatment of tuberculosis (TB) in solid organ transplant (SOT) recipients is challenging owing to interactions between rifampin and immunosuppressive drugs. Rifabutin, a rifamycin with excellent activity against Mycobacterium tuberculosis and that induces cytochrome p450 less, may facilitate treatment. We report our experience with rifabutin for treating TB in SOT recipients and review the available literature. Methods A retrospective observational study of all SOT recipients with TB between January 2000 and December 2019. The clinical characteristics and outcomes of patients treated with and without rifabutin‐containing regimens were compared and a literature review was conducted. Results We included 31 SOT recipients with TB, among whom 22 (71%) were men and the median age was 62 years (interquartile range 50‐20). There were no significant differences between patients treated with rifabutin (n = 12), rifampin (n = 14), and non‐rifamycins (n = 5) in clinical cure rates (83.3%, 64.3%, and 100%, respectively; P = .21), side effects (25%, 37.5%, and 20%, respectively; P = .74), or mortality (16.7%, 35.7%, and 0%, respectively; P = .21). Only one patient, treated with rifampin, suffered graft rejection. The literature review identified 59 SOT recipients with TB treated with rifabutin‐containing regimens from 8 publications. Overall, the clinical cure, graft rejection, and mortality rates were 93.2%, 5.1%, and 6.8%, respectively. Conclusions Rifabutin‐containing regimens offer a reliable alternative to rifampin when treating TB in SOT recipients.

Mycobacterium tuberculosis in solid organ transplant donors and recipients

“…Multiple studies have demonstrated that the development of posttransplant TB is associated with significant mortality [8 ▪ ,9–11,13,51,53,54 ▪▪ ,55,56], graft rejection or graft failure [9,10,12,13,55–58]. A recent systematic review and meta-analysis estimated the prevalence of TB disease in SOT at 3%; however, these estimates were mostly from middle to high-incidence countries [3 ▪ ].…”

“…Posttransplant TB can present with fever alone mandating a high clinical suspicion, particularly in those with risk factors [11,13,53,56,58,59]. Pulmonary TB (PTB) is generally common (47–87%), followed by extrapulmonary TB (EPTB) (11–41%), disseminated (2–23%), and miliary TB (2–8%) [3 ▪ ,8 ▪ ,9,10,13,53,54 ▪▪ ,56,57]. However, EPTB and disseminated TB were observed in 85% and 66%, respectively, in a single-center study [11].…”

Mycobacteria: Selection of Transplant Candidates and Post–lung Transplant Outcomes

“…36,37 To address the concern of rifampin use after transplant, rifabutin has been substituted to treat active TB following SOT with success. 38,39 Nontuberculous mycobacteria…”

Drug‐level change and optimal dose adjustment of tacrolimus with the use of rifabutin for treating mycobacterial disease in solid organ transplant recipients

“…Therefore, a rifampin‐sparing regimen has been attempted in SOT recipients to avoid this risk of lower bioavailability of an immunosuppressive agent 16,17 . Alternatively, rifabutin can be chosen as a reliable substitute to rifampin in these patients, 18,19 considering that rifabutin has comparable potent activity against M. tuberculosis with rifampin, 20 although rifabutin is a less potent inducer of the cytochrome P450 3A4 microsomal enzyme 21–23 …”

“…[13][14][15] Therefore, a rifampin-sparing regimen has been attempted in SOT recipients to avoid this risk of lower bioavailability of an immunosuppressive agent. 16,17 Alternatively, rifabutin can be chosen as a reliable substitute to rifampin in these patients, 18,19 considering that rifabutin has comparable potent activity against M. tuberculosis with rifampin, 20 although rifabutin is a less potent inducer of the cytochrome P450 3A4 microsomal enzyme. [21][22][23] However, as previous studies on the clinical experience of the use of rifabutin in SOT recipients have been limited, little is known about the change in the drug level and need for dose adjustment of calcineurin inhibitor when calcineurin inhibitor used with rifabutin.…”