Levofloxacin for BK virus prophylaxis following kidney transplantation: a randomized clinical trial.
OBJECTIVE
BK virus infection is a significant complication of modern immunosuppression used in kidney transplantation. Viral reactivation occurs first in the urine (BK viruria) and is associated with a high risk of transplant failure. There are currently no therapies to prevent or treat BK virus infection. Quinolone antibiotics have antiviral properties against BK virus but efficacy at preventing this infection has not been shown in prospective controlled studies.


OBJECTIVE
To determine if levofloxacin can prevent BK viruria in kidney transplant recipients.


METHODS
Double-blind, placebo-controlled randomized trial involving 154 patients who received a living or deceased donor kidney-only transplant in 7 Canadian transplant centers between December 2011 and June 2013.


METHODS
Participants were randomly assigned to receive a 3-month course of levofloxacin (500 mg/d; n = 76) or placebo (n = 78) starting within 5 days after transplantation.


METHODS
The primary outcome was time to occurrence of BK viruria (detected using quantitative real-time polymerase chain reaction) within the first year after transplantation. Secondary outcomes included BK viremia, peak viral load, rejection, and patient and allograft survival.


RESULTS
The mean follow-up time was 46.5 weeks in the levofloxacin group and 46.3 weeks in the placebo group (27 patients had follow-up terminated before the end of the planned follow-up period or development of viruria because the trial was stopped early owing to lack of funding). BK viruria occurred in 22 patients (29%) in the levofloxacin group and in 26 patients (33.3%) in the placebo group (hazard ratio, 0.91; 95% CI, 0.51-1.63; P = .58). There was no significant difference between the 2 groups in regard to any of the secondary end points. There was an increased risk of resistant infection among isolates usually sensitive to quinolones in the levofloxacin group vs placebo (14/24 [58.3%] vs 15/45 [33.3%], respectively; risk ratio, 1.75; 95% CI, 1.01-2.98) as well as a nonsignificant increased risk of suspected tendinitis (6/76 [7.9%] vs 1/78 [1.3%]; risk ratio, 6.16; 95% CI, 0.76-49.95).


CONCLUSIONS
Among kidney transplant recipients, a 3-month course of levofloxacin initiated early following transplantation did not prevent BK viruria. Levofloxacin was associated with an increased risk of adverse events such as bacterial resistance. These findings do not support the use of levofloxacin to prevent posttransplant BK virus infection.


BACKGROUND
clinicaltrials.gov Identifier: NCT01353339.
Division of Nephrology, Kidney Research Centre, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada2Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of O.
Greg A
GA
Knoll
Department of Medicine, Toronto General Hospital, University of Toronto, Ontario, Canada.
Atul
A
Humar
Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Dean
D
Fergusson
Department of Medicine, Vancouver General Hospital, Vancouver, British Columbia, Canada.
Olwyn
O
Johnston
Department of Medicine, Western University and London Health Sciences Centre, London, Ontario, Canada.
Andrew A
AA
House
Department of Medicine, Toronto General Hospital, University of Toronto, Ontario, Canada.
S Joseph
SJ
Kim
Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Tim
T
Ramsay
Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Michaël
M
Chassé
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, Canada.
Xiaoli
X
Pang
Department of Medicine, St Michael's Hospital, Toronto, Ontario, Canada.
Jeff
J
Zaltzman
Department of Medicine, University of Alberta, Edmonton, Canada.
Sandra
S
Cockfield
Department of Medicine, McGill University Health Center, Montreal, Quebec, Canada.
Marcelo
M
Cantarovich
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Martin
M
Karpinski
Clinical Epidemiology Program, Ottawa Hospital Research Institute, and Department of Epidemiology and Community Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Louise
L
Lebel
Department of Medicine, St Paul's Hospital, Vancouver, British Columbia, Canada12Center for Health Evaluation and Outcomes Sciences, University of British Columbia, Vancouver, British Columbia, Canada13Tufts-New England Medical Center, Boston, Massachuset.
John S
JS
Gill
D000328:Adult; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D019072:Antibiotic Prophylaxis; D001739:BK Virus / Q000235:genetics / Q000302:isolation & purification*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D016030:Kidney Transplantation; D064704:Levofloxacin / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D027601:Polyomavirus Infections / Q000517:prevention & control*; D011446:Prospective Studies; D014412:Tumor Virus Infections / Q000517:prevention & control*; D014556:Urine / Q000821:virology; D019562:Viral Load; D014766:Viremia
D000900:Anti-Bacterial Agents; D064704:Levofloxacin