PREVENTION OF ARRHYTHMIA DEVICE INFECTION TRIAL (PADIT) CLUSTER CROSSOVER
STUDY

Infection is a potentially catastrophic consequence of device surgery, managed
with device removal and lead extraction. Lead extraction is associated with
major complications (0.5-2.4% mortality!).
Pocket infections are reported in up to 0.7% of primo implants and up to 1.7%
in device replacements and lead repositioning.

Current AHA/ACC guidelines advocate a single dose of preoperative antibiotics
in patients undergoing arrhythmia device implantation. These guidelines state:
**primary prevention of device-related infection has not been examined in
prospective randomized trials. This is due in
part to the infrequency of infection. Nevertheless primary prophylaxis is
routinely given**.
There is however a rationale for using both cefazolin and vancomycin before the
procedure to increase the level of prophylaxis. Most device infections are due
to Gram-positive bacteria, mainly Coagulase-negative staphylococci (CoNS) and
S.aureus that are frequently
resistant to beta-lactam antibiotics.

The purpose of the study is to test whether a centre-wide policy of incremental
antibiotic therapy will reduce arrhythmia device infection in patients
undergoing arrhythmia device procedures compared to a policy of conventional
antibiotic prophylaxis

A prospective, randomized, unblinded cluster crossover design will track the
outcome of high infection risk patients undergoing an arrhythmia device
procedure. Centres will be randomised to conventional vs. incremental
antibiotic therapy for prevention of device infection, and will
cross over after 6 months to the alternate strategy. At one year centres will
be re-randomised and then 6 months following, will cross over again. The
crossover will mitigate the risk that changes in practice or in pathogens will
contaminate results.
A wash in period of one week prior to each therapy will allow for the
transition to the alternate therapy. As these therapies will be integrated into
standard management, during each treatment period the randomized antibiotic
therapy will be used on all patients undergoing a device implant
procedure at the centre.
Study outcomes will be adjudicated in a blinded fashion.

CONVENTIONAL THERAPY
a single preoperative dose of intravenous Cefazolin 1-2g iv 60 minutes prior to
skin incision.
In penicillin-allergic patients, Vancomycin will be used instead at a dose of
1-1.5g iv given over 60-90 minutes, 60-90 minutes prior to skin incision.

INCREMENTAL THERAPY
- Pre-procedure a single dose of both Cefazolin 1-2g iv 60 minutes prior to
skin incision plus a single dose of Vancomycin 1-1.5g iv given over 60-90
minutes, 60-90 minutes prior to incision.
Because only a single dose of Vancomycin is administered, there is no need to
adjust dosing in patients with renal failure.
Penicillin-allergic patients will only receive Vancomycin.

- intracavitary antibacterial wash with 1 gr cefazolin diluted in 50 ml sterile
saline in a bowl on the sterile field, and injected into the pocket.

- postoperative antibiotic prescription to last for 2 days after the procedure.
This can be either Cefalexin 500 mg PO TID OR Cephadroxil 1000 mg BID.
Penicillin-allergic patients will receive Clindamycin 150-300 mg TID.

All the antibiotics used as part of this research study are widely used in the
Netherlands to prevent surgical infections and are generally considered to be
low risk. However all antibiotics can sometimes have unwanted side effects.
Vancomycin can cause a rash or reduced blood pressure (3-11%) however; this
risk will be minimized by delivering the drug intravenously at a slow rate.
Other side effects of the antibiotic include a temporary drop in white blood
cells (1-2%), allergic rash (3%), fever (2%) and temporary reduction in kidney
function. Cefazolin, Cephadroxil and Cephalexin can cause a rash in 1-7% of
patients who receive them or diarrhea in 1-20%, which occasionally is severe.
Should you be allergic to penicillin, clindamycin may be provided which can
cause diarrhea in up to 20% of patients, which occasionally is severe.
Occasionally, people may also develop a rash or temporary liver problems,
usually with no symptoms.