Tuberculosis (TB) treatment without rifampin in kidney (K) and kidney-pancreas (KP) transplantation (TX)
Marcelo Radisic1, Natalia Pujato1, Pablo M. Bravo1, Roxana Del Grosso2, Martin Hunter2, Santiago Beltramino3, Lucia Cornet1, Maria del Carmen Rial4, Rosa Livia Franzini4, Ana C. Dotta4, Luis Leon4, Javier Walther4, Pablo Uva5, Gustavo Werber3.
1Infectious Diseases, Instituto de Trasplante y Alta Complejidad (ITAC), Ciudad Autonoma de Buenos Aires, Argentina; 2Internal Medicine, Instituto de Trasplante y Alta Complejidad (ITAC), Ciudad Autonoma de Buenos Aires, Argentina; 3Intensive Care Unit, Instituto de Trasplante y Alta Complejidad (ITAC), Ciudad Autonoma de Buenos Aires, Argentina; 4Kidney Transplantation, Instituto de Trasplante y Alta Complejidad (ITAC), Ciudad Autonoma de Buenos Aires, Argentina; 5Kidney Pancreas Transplantation, Instituto de Trasplante y Alta Complejidad (ITAC), Ciudad Autonoma de Buenos Aires, Argentina
Introduction: TB is a diagnostic and therapeutic challenge in K/ KP Tx. Pharmacokinetic interaction between rifampin (RFP) and mTOR /calcineurin inhibitors (CNI) led to use of alternative regimens for TB treatment in this group of patients. Results obtained in TB treatment with RFP-free regimens in K/KP TX patients are presented.
Methods: Retrospective review of confirmed TB cases in K /KP Tx patients. (Jan 2006-Jul 2019), defined by M.tuberculosis positive culture or PCR; o elevated adenosine deaminase (ADA) and/or characteristic histopathology findings with clinical evolution consistent with TB. Cases defined by response to empiric treatment were excluded.
Results: 57 TB cases (50 in 2297adults with KTx (2.2%) /7 in 364 KPTx (1.92%), Two were postmortem diagnosis (excluded from analysis). “De novo” Treatment with RFP-free regimens: 30 patients (pts) (25 KTx, 5 KPTx). Mean age: 49.24 (∓11.50) years. Induction immunosuppression (IS): 22 pts. Maintenance IS: tacrolimus-mycofenolate (MF)-steroids (E) in 13 (43%), sirolimus-MF-E in 6 (20%), Other IS regimens: 11(36%). Belatacept in 4 patients. (13%). 22 pts without rejections (R) prior to TB, (8 pts with R: Rejection rate prior to TB 0.15 episodes/year/patient. TB onset after TX: Median 28 (range 2.4- 242.3) months. Late onset (> 6 months): 24 cases (80%). TB: pulmonary = 13 (43%); Diseminated = 7 (23%) Extrapulmonary = 10 (33%). All patients were treated with isoniazid (IHN), ethambutol (EMB), levofloxacin (L), 12 patientes also received pyrazinamide (PZN) during the first 2 months. 27 (90%) patients completed treatment with IHN-EMB-L x 6 months (1), 9 months (3) o 12 months (23). In these patients, graf function had no change (mean initial creatinine 1.5 mg%, mean creatinine at end of treatment 1.5 mg%, p=NS). One patient returned to dialysis at 4th month of treatment, and completed with IHN-RFP. 2 (7%) patients died while on treatment. Among the 28 patients who completed treatment, median (range) follow-up was 32 (8-150) months. No TB relapses were observed.
Conclusions: Rifampin-free TB treatment in K/KP Tx was safe and effective. Mortality was less than observed in series with a larger number of patients treated with rifampin. The use of RFP-free regimens also avoided cumbersome pharmacokinetic interactions with CNI/mTOR, with excellent results in grafts function.
