Meeting NewsPerspective

Alternative antibiotic strategy modestly improves cardiac device infection rate

Andrew D. Krahn MD, FHRS
Andrew D. Krahn

BOSTON — A novel antibiotic strategy lowered the infection rate in patients undergoing surgery related to implantable cardiac devices, but the difference compared with the usual care IV cefazolin alone was not significant, according to new data from the PADIT trial.

The alternative antibiotic strategy consisted of a single preoperative dose of IV cefazolin and vancomycin, an intraoperative bacitracin pocket wash and oral cephalosporin for 2 days after cardiac device surgery.

Currently, the only guideline recommendation to prevent such infections is administration of IV cefazolin, but methicillin-resistant gram-positive microorganisms do not respond to cefazolin, Andrew D. Krahn, MD, FHRS, head of the division of cardiology at the University of British Columbia in Vancouver, said during a presentation at the Heart Rhythm Society Annual Scientific Sessions.

When these patients get infections, “they undergo risky invasive procedures, end up having to have the device removed, and need a long course of antibiotics and then surgery afterwards to implant the new device,” Krahn said during a press conference. “This occurs in 2% of patients. When something catastrophic happens to 2% of patients, you need a very large-scale study to address that question.”

The PADIT study was conducted to assess whether an incremental regimen of perioperative antibiotics would reduce device-related infections compared with IV cefazolin. Krahn and colleagues randomly assigned 28 centers in Canada and the Netherlands to administer the incremental regimen or IV cefazolin to 19,603 patients undergoing cardiac device procedures (mean age, 72 years; 34% women). Each site crossed over to the other strategy after 6 months. At 12 months, the sites were re-randomized, and then crossed over to the other strategy at 18 months.

All centers included high-risk patients, defined as those who had a repeat procedure in the arrhythmia device pocket such as a generator change, a lead or pocket procedure or an upgrade; or those implanted with a cardiac resynchronization therapy device. Six centers also included low-risk patients, defined as those who had a pacemaker or implantable cardioverter defibrillator implanted for the first time.

The primary outcome was hospitalization attributed to device infection. Patients were followed for 1 year after the 2-year enrollment period. The trial was designed with a projected infection rate of 2% per year, and the primary analysis included the high-risk patients, Krahn said.

According to data reported at the HRS Scientific Sessions, the primary outcome was modestly lower in the incremental group (0.78% vs. 1.03%; OR = 0.77; 95% CI, 0.56-1.05).

“The infection rates we expected to be about 2% were 1%,” Krahn said at the press conference. “The [incremental strategy] reduced the rate of infection by about 20%, but did not achieve statistical significance.”

The results were consistent across subgroups. “I interpret that as there is a modest effect, but it was too small for this kind of study to detect that effect and find it significant,” Krahn said. “We were seeking a definitive result that would have established this treatment as mandatory. That did not take place. I believe providers will look for the patients they believe to be at highest risk, and consider the incremental investment for them.”

Adverse events were low and similar between the groups aside from allergic reactions, which were higher in the incremental group (0.2% vs. 0.1%; P = .018).

“The downsides to doing [the incremental strategy] were pretty trivial,” Krahn said.

The lower-than-expected infection rate “may reflect the Hawthorne Effect: If you measure and tell people you’re watching, that creates a fastidious culture of attention to detail,” he said. – by Erik Swain

Reference:

Krahn AD, et al. LBCT01-01. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 9-12, 2018; Boston.

Disclosure: Krahn reports he received research grants from Boston Scientific and Medtronic and compensation for services from Medtronic.

Andrew D. Krahn MD, FHRS
Andrew D. Krahn

BOSTON — A novel antibiotic strategy lowered the infection rate in patients undergoing surgery related to implantable cardiac devices, but the difference compared with the usual care IV cefazolin alone was not significant, according to new data from the PADIT trial.

The alternative antibiotic strategy consisted of a single preoperative dose of IV cefazolin and vancomycin, an intraoperative bacitracin pocket wash and oral cephalosporin for 2 days after cardiac device surgery.

Currently, the only guideline recommendation to prevent such infections is administration of IV cefazolin, but methicillin-resistant gram-positive microorganisms do not respond to cefazolin, Andrew D. Krahn, MD, FHRS, head of the division of cardiology at the University of British Columbia in Vancouver, said during a presentation at the Heart Rhythm Society Annual Scientific Sessions.

When these patients get infections, “they undergo risky invasive procedures, end up having to have the device removed, and need a long course of antibiotics and then surgery afterwards to implant the new device,” Krahn said during a press conference. “This occurs in 2% of patients. When something catastrophic happens to 2% of patients, you need a very large-scale study to address that question.”

The PADIT study was conducted to assess whether an incremental regimen of perioperative antibiotics would reduce device-related infections compared with IV cefazolin. Krahn and colleagues randomly assigned 28 centers in Canada and the Netherlands to administer the incremental regimen or IV cefazolin to 19,603 patients undergoing cardiac device procedures (mean age, 72 years; 34% women). Each site crossed over to the other strategy after 6 months. At 12 months, the sites were re-randomized, and then crossed over to the other strategy at 18 months.

All centers included high-risk patients, defined as those who had a repeat procedure in the arrhythmia device pocket such as a generator change, a lead or pocket procedure or an upgrade; or those implanted with a cardiac resynchronization therapy device. Six centers also included low-risk patients, defined as those who had a pacemaker or implantable cardioverter defibrillator implanted for the first time.

The primary outcome was hospitalization attributed to device infection. Patients were followed for 1 year after the 2-year enrollment period. The trial was designed with a projected infection rate of 2% per year, and the primary analysis included the high-risk patients, Krahn said.

According to data reported at the HRS Scientific Sessions, the primary outcome was modestly lower in the incremental group (0.78% vs. 1.03%; OR = 0.77; 95% CI, 0.56-1.05).

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“The infection rates we expected to be about 2% were 1%,” Krahn said at the press conference. “The [incremental strategy] reduced the rate of infection by about 20%, but did not achieve statistical significance.”

The results were consistent across subgroups. “I interpret that as there is a modest effect, but it was too small for this kind of study to detect that effect and find it significant,” Krahn said. “We were seeking a definitive result that would have established this treatment as mandatory. That did not take place. I believe providers will look for the patients they believe to be at highest risk, and consider the incremental investment for them.”

Adverse events were low and similar between the groups aside from allergic reactions, which were higher in the incremental group (0.2% vs. 0.1%; P = .018).

“The downsides to doing [the incremental strategy] were pretty trivial,” Krahn said.

The lower-than-expected infection rate “may reflect the Hawthorne Effect: If you measure and tell people you’re watching, that creates a fastidious culture of attention to detail,” he said. – by Erik Swain

Reference:

Krahn AD, et al. LBCT01-01. Presented at: Heart Rhythm Society Annual Scientific Sessions; May 9-12, 2018; Boston.

Disclosure: Krahn reports he received research grants from Boston Scientific and Medtronic and compensation for services from Medtronic.

    Perspective

    The interesting finding in PADIT is that the rate of device infection was low in both arms. A lot of registries and Medicare data had raised concern about infection during device surgery to the point of where it was almost getting out of control. For quite some time, we have argued that this might be a false impression of the problem. The problem is serious because the consequences are great. Mortality in the year after device infection is very high, close to 20% of all-comers.

    What we lacked in previous studies is a clear understanding of the true denominator. While the rate may not have been changing from year to year, we were seeing more infections each year because many patients who got infections in previous years were still alive. These patients are still at risk and require more procedures. That’s the issue with categorizing the problem by event rate.

    I commend everyone involved with the study for keeping the event rates so low. This is a remarkable accomplishment, especially since many of the procedures were redo procedures. I will be interested to see more details about the patients when the findings are published.

    Also of interest is the progress of WRAP-IT, a randomized trial of patients undergoing device replacements or upgrades or de novo CRT defibrillator, as opposed to a cluster-randomization trial like PADIT. WRAP-IT will assess the effectiveness of the antibiotic envelope in reducing cardiac implantable electronic device infection. It should build more knowledge about the true event rates for truly high-risk patients.

    • Khaldoun Tarakji, MD, MPH
    • Cardiology Today Next Gen Innovator
      Staff Physician
      Section of Electrophysiology and Pacing
      Robert and Suzanne Tomsich Department of Cardiovascular Medicine
      Sydell and Arnold Miller Family Heart & Vascular Institute
      Cleveland Clinic

    Disclosures: Tarakji reports he is national principal investigator for the WRAP-IT trial and serves on advisory boards for AliveCor and Medtronic.

    Perspective

    Jagmeet P. Singh

    This study examined the impact of two different periprocedural antibiotic regimens at the time of device implant. The incremental strategy of adding a single dose of vancomycin preoperatively along with intraoperative bacitracin pocket wash and 2 days of oral cephalosporin postoperatively had no significant additional impact on reducing infections. Furthermore, there were no identifiable subgroups of high-risk patients that benefited more than the others. Notably, the overall infection rate was markedly lower than expected. We should aim to emulate our Canadian colleagues, who have done very well by reducing device infection rates quite dramatically.

    • Jagmeet P. Singh, MD, DPhil, FACC, FHRS
    • Cardiology Today Editorial Board Member
      Massachusetts General Hospital Heart Center
      Harvard Medical School

    Disclosures: Singh reports he receives consultant fees from Abbott, Boston Scientific, Biotronik, EBR, Impulse Dynamics, LivaNova, Medtronic and Toray Inc.

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