Tuberculosis prophylaxis with levofloxacin in liver transplant patients is associated with a high incidence of tenosynovitis: safety analysis of a multicenter randomized trial
Torre-Cisneros J(1), San-Juan R(2), Rosso-Fernández CM(3), Silva JT(2), Muñoz-Sanz A(4), Muñoz P(5), Miguez E(6), Martín-Dávila P(7), López-Ruz MA(8), Vidal E(1), Cordero E(3), Montejo M(9), Blanes M(10), Fariñas MC(11), Herrero JI(12), Rodrigo J(13), Aguado J(M2).
(1) Hospital Universitario Reina Sofía-IMIBIC-UCO, Córdoba.
(2) Hospital Universitario 12 de Octubre, Madrid.
(3) Hospital Universitario Virgen del Rocío, Sevilla.
(4) Hospital Universitario Infanta Cristina, Badajoz.
(5) Hospital Universitario Gregorio Marañon, Madrid.
(6) Complejo Hospitalario Universitario a Coruña.
(7) Hospital Universitario Ramón y Cajal, Madrid.
(8) Hospital Universitario Virgen de la Nieves, Granada.
(9) Hospital Universitario de Cruces, Bilbao.
(10) Hospital Universitario La Fe, Valencia.
(11) Hospital Universitario Marqués de Valdecilla, Santander.
(12) Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREehd) Clínica Universitaria de Navarra, Pamplona.
(13) Red Española de Investigación en Patología Infecciosa (REIPI), Hospital Universitario Carlos Haya, Málaga, Spain.
It is necessary to develop a safe alternative to isoniazid for tuberculosis prophylaxis in liver transplant recipients. This study was designed to investigate the efficacy and safety of levofloxacin.
An open-label, prospective, multicenter, randomized study was conducted to compare the efficacy and safety of levofloxacin (500 mg q24h for 9 months) initiated in patients awaiting liver transplantation and isoniazid (300 mg q24h for 9 months) initiated post-transplant when liver function was stabilized. Efficacy was measured by tuberculosis incidence at 18 months after transplantation. All adverse events related to the medication were recorded.
CONSORT guidelines were followed in order to present the results. The safety committee suspended the study through a safety analysis when 64 patients had been included (31 in the isoniazid arm and 33 in the levofloxacin arm). The reason for suspension was an unexpected incidence of severe tenosynovitis in the levofloxacin arm (18.2%). Although the clinical course was favorable in all cases, tenosynovitis persisted for 7 weeks in some patients. No patients treated with isoniazid, developed tenosynovitis. Only 32.2% of patients randomized to isoniazid (10/31) and 54.5% of patients randomized to levofloxacin (18/33, P = .094) completed prophylaxis. No patient developed tuberculosis during the study follow-up (median 270 days).
Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.
CITATION Clin Infect Dis. 2015 Jun 1;60(11):1642-9. doi: 10.1093/cid/civ156.