Ciprofloxacin for Prevention of BK Infection

BK virus is a member of the virus family polyomaviridae ("polyoma"). The virus, which can
manifest as a viral nephritis, was first described in a renal transplant recipient in 1971,
however it was not until the past decade that infection with BK virus became known as an
important contributor to graft dysfunction and graft loss after renal transplantation. It
has been widely accepted that emergence of BK virus correlates with the more potent
immunosuppressive agents currently used to lower acute rejection rates. In contrast to other
opportunistic infections after transplantation, for which routine prophylactic agents are
administered, there is no effective agent for the prevention of BK infection, nor is there
an effective agent for treating BK infection once it occurs.

Ciprofloxacin is a well known anti-infective agent in the fluoroquinolone class of
antibiotics. It is most active against gram-negative enteric pathogens, and is commonly used
for a variety of infectious indications.

Though classified as antibacterial agents, fluoroquinolones have been suggested to exhibit
anti-BK viral effects by interfering with helicase activity of the BK virus large T antigen.
Ciprofloxacin has been shown in previous studies to reduce urine BK viral load, and
BK-associated hemorrhagic cystitis in the stem cell transplant population. Ciprofloxacin has
also been associated with a lower incidence of BK viremia in one retrospective study in
kidney transplant recipients. Based on these reports, the investigators hope to find a
reduction BK viremia and BK nephropathy using a prospective, randomized study design.

Inclusion Criteria:

- Male or female subjects over the age of 18 years

- Recipients of a primary or repeat renal allograft either alone (from a deceased or
living donor) or as a dual-kidney transplant

- Signed informed consent form prior to any research assessment

Exclusion Criteria:

- Patients with known severe allergy to ciprofloxacin

- History of tendon rupture or tendinitis

- Use of antiarrythmic drugs known to prolong the QT interval such as class IA
antiarrhythmic drugs (e.g. quinidine, procainamide, disopyramide), class III
antiarrhythmic drugs (e.g. amiodarone, sotalol)

- Patients with history of previous non-renal transplantation

- Recipients administered rituximab within one year prior to transplantation, or
recipients expected to receive rituximab as part of desensitization strategy or for
the presence of historical donor specific antibodies

- QTc interval interval of greater than 500 msec on admission or post-operative EKG

- BK nephropathy with previous transplant

- BK viremia on admission

- Any condition present during the initial transplant hospitalization that in the
investigator's judgment would increase the risk associated with participation in the
study