Tuberculosis prophylaxis with levofloxacin in liver transplant patients is associated with a high incidence of tenosynovitis: safety analysis of a multicenter randomized trial.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
Levofloxacin prophylaxis of tuberculosis in liver transplant candidates is associated with a high incidence of tenosynovitis that limits its potential utility.
Hospital Universitario Reina Sofía-IMIBIC-UCO, Córdoba.
Julian
J
Torre-Cisneros
Hospital Universitario 12 de Octubre, Madrid.
Rafael
R
San-Juan
Hospital Universitario Virgen del Rocío, Sevilla.
Clara M
CM
Rosso-Fernández
Hospital Universitario 12 de Octubre, Madrid.
J Tiago
JT
Silva
Hospital Universitario Infanta Cristina, Badajoz.
Agustin
A
Muñoz-Sanz
Hospital Universitario Gregorio Marañon, Madrid.
Patricia
P
Muñoz
Complejo Hospitalario Universitario a Coruña.
Enrique
E
Miguez
Hospital Universitario Ramón y Cajal, Madrid.
Pilar
P
Martín-Dávila
Hospital Universitario Virgen de la Nieves, Granada.
Miguel Angel
MA
López-Ruz
Hospital Universitario Reina Sofía-IMIBIC-UCO, Córdoba.
Elisa
E
Vidal
Hospital Universitario Virgen del Rocío, Sevilla.
Elisa
E
Cordero
Hospital Universitario de Cruces, Bilbao.
Miguel
M
Montejo
Hospital Universitario La Fe, Valencia.
Marino
M
Blanes
Hospital Universitario Marqués de Valdecilla, Santander.
M Carmen
MC
Fariñas
Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREehd) Clínica Universitaria de Navarra, Pamplona.
Jose Ignacio
JI
Herrero
Red Española de Investigación en Patología Infecciosa (REIPI), Hospital Universitario Carlos Haya, Málaga, Spain.
Juan
J
Rodrigo
Hospital Universitario 12 de Octubre, Madrid.
Jose Maria
JM
Aguado
D000328:Adult; D000368:Aged; D019072:Antibiotic Prophylaxis / Q000009:adverse effects* / Q000379:methods; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D064704:Levofloxacin / Q000008:administration & dosage / Q000009:adverse effects*; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013717:Tenosynovitis / Q000139:chemically induced* / Q000453:epidemiology*; D066027:Transplant Recipients; D016896:Treatment Outcome; D014376:Tuberculosis / Q000517:prevention & control*
D000995:Antitubercular Agents; D064704:Levofloxacin
investigator-driven clinical trial; levofloxacin; tenosynovitis; tuberculosis