Tolerability of Fluoroquinolones in Management of Latent Tuberculosis in Liver Transplant Candidates.

TO THE EDITOR—Recently, Torre-Cisneros and colleagues [1] raised concerns about the safety of using levofloxacin for tuberculosis prophylaxis in liver transplant patients. In their study, 11 out of 33 patients in the levofloxacin arm developed adverse effects, including 5 with tenosynovitis. Only 18 (54.5%) of the patients completed tuberculosis prophylaxis with levofloxacin, and the study was suspended due to safety concerns. Their findings differ from our experience, which we would like to share here. At Stanford, our standard of care is to treat latent tuberculosis prior to liver transplant whenever possible. Regimens include isoniazid (INH) × 9 months, rifampin (RIF) × 4 months, or a fluoroquinolone (FQ) × 9 months when there is concern for potential INH or RIF hepatotoxicity. Per our retrospective chart review, 44 liver transplant candidates with positive tuberculosis interferon-gammarelease-assays were started on tuberculosis prophylaxis during the pretransplant period from 2006 to 2014. Twenty-five patients received FQ (17 levofloxacin and 8 moxifloxacin), 10 received INH, and 9 received RIF (Table 1). Adverse events were observed in 14 of 25 FQtreated patients, including 4 (16%) that developed musculoskeletal symptoms ranging from diffuse joint pain to unilateral tendinopathy. Importantly, only one patient with musculoskeletal symptoms required permanent discontinuation of the drug. In the other 3 cases, symptoms resolved after a temporary hold of the FQ, close monitoring, and rechallenge; these patients subsequently completed the full 9-month course of prophylaxis. One additional patient required discontinuation of FQ due to severe fatigue. An additional 6 patients received FQs post-transplant for tuberculosis prophylaxis; of these, only one reported diffuse joint pain but was ultimately one of 5 patients that completed prophylaxis; one did not complete prophylaxis due to death unrelated to tuberculosis (data not shown). We did not observe hepatotoxicity (defined as liver enzyme abnormalities greater than twice the upper limit of normal) linked to FQ use, either preor post-transplant. None of the treated patients have developed tuberculosis reactivation with a median follow-up time of 46 months (range 21–75). As Torre-Cisneros et al have noted [1], levofloxacin, although linked to tendinitis and tendon rupture, is generally a safe drug. Adverse drug reactions linked to FQs do not always require discontinuation of therapy [2]. In fact, previous studies record the discontinuation rate of levofloxacin in clinical trials at approximately 4% [3]. Our experience is that some adverse effects reported by patients on FQ may be nonspecific and, although they require an abundance of caution, may not always necessitate cessation of the Table 1. Outcomes and Adverse Events Associated With Latent Tuberculosis Treatment in Liver Transplant Candidates