The past several years have seen a significant decrease in healthcare-associated infections, in particular central line-associated bloodstream infections and certain surgical site infections. There is, however, one major exception to this successful trend. Infections associated with cardiac implantable electronic devices have not only persisted, but have actually been increasing.
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Consider this fact alone: CIED implants increased by 96 percent over a 15-year period, and the incidence of CIED-related infection increased by more than double that rate (210 percent), according to a study in the Journal of the American College of Cardiology. Such infections may not only have potentially serious — even fatal — consequences for patients, but they may also result in higher healthcare costs for hospitals.
As noted by Ibrahim Hanna, MD, director of cardiac electrophysiology at Baptist Health Centers in Birmingham, Ala., "The rates [of CIED-related] infections have been steadily increasing. We're seeing not only more infections, but also more serious infections, despite the best efforts of physicians."
Risk factors behind the rising incidence
Which risk factors may be contributing to this dramatic increase in CIED infections? Several have been identified, in particular older implant patients burdened with more comorbidities. Because patients are living longer, they are more likely to need a CIED. In turn, implants may also need to be revised, replaced or upgraded at a later time.
Other factors may include longer procedures, as well as the presence of organisms increasingly resistant to antibiotics. Certain organisms, coagulase-negative Staphylococcus and S. aureus (S. epidermidis, MSSA, MRSA) for instance, which are known to be responsible for approximately 70 percent of CIED infections, are increasingly resistant to the antibiotic methicillin. As noted by Dr. Hanna, this increase in antibiotic resistance has made infections more difficult to prevent and more difficult to treat.
Risk factor importance assessed by odds ratio
Odds ratios quantify a patient's risk of infection based on their particular medical characteristics and history, the medications they take and medical procedures they have undergone. Renal failure, to cite one example, has an odds ratio of 11.97; a patient with renal failure is approximately 12 times more likely to get a CIED infection than a patient who does not have renal failure.
Other significant risk factors for CIED infection include early re-intervention (odds ratio 15.4), use of corticosteroids (13.9), diabetes (3.5) and device replacement or revision (3.67).
In relation to device replacement, Christopher Ellis, MD, director of cardiac electrophysiology at Vanderbilt University Medical Center in Nashville, Tenn., shares that "patients in the last five to 10 years are living longer, and I'm doing more and more device change-outs [replacements], and those specifically have much higher infection rates than a new implant." Two clinical studies published in the journals Circulation and Heart Rhythm had similar findings.
Worsened patient outcomes and increased treatment costs
Regardless of risk factor, the increase in infection rates has a significant impact not just on treatment outcomes, but also on healthcare costs.
Statistics reveal that preventing CIED infections can, in fact, be the difference between life and death. In a study published in the Archives of Internal Medicine, patients with CIED infection experience relatively higher admission mortality rates, as well as lower survival rates beyond three years, even after successful treatment of the infection.
As a result, "The economic consequences, including healthcare resource utilization, of CIED infections are substantial," according to the American Heart Association. Hospitals may be financially penalized by CMS when a patient undergoing a CIED procedure acquires an infection during their hospital stay.
In several studies, CIED infections cost a healthcare facility an average of approximately $52,000, with some costs exceeding well over $100,000. "The big question in the near future is who is going to pay for that," Dr. Ellis notes.
The solution may lie in novel perioperative technology
Dr. Hanna's practice has taken several approaches to help reduce instances of CIED infections to zero. One tool he has added to his arsenal is the TYRX Absorbable Antibacterial Envelope.
FDA-cleared in May 2013, the fully absorbable TYRX Envelope, made from a large-pore knitted mesh coated with a bioabsorbable polymer holds a CIED securely in place to provide a stable environment when implanted in the body. This stability, studies show, helps keep the CIED from moving or twisting, which can reduce its effectiveness.
Within two hours of implantation, the TYRX Envelope elutes therapeutic levels of the antibiotics minocycline and rifampin locally into the tissue pocket; this elution of antibiotics continues over a minimum of seven days. The TYRX Envelope is fully absorbed by the body about nine weeks after the procedure. Additionally, the TYRX Envelope requires no adjustment to standard surgical techniques during revision or upgrade procedures.
Dr. Ellis also started using the TYRX Envelope to more effectively protect his patients from CIED infections approximately four years ago.
Even though the Envelope may be used on any patient with an implanted device, many physicians, like Drs. Thomas, Ellis and Hanna, have opted to use it only on patients at the highest risk of developing a CIED infection.
"We don't use it on everybody, but we do use it on people with multiple risk factors for infection," Dr. Ellis explains. "By limiting use, we keep costs down and have gotten the best benefit we can from the product."
Proven effective at reducing CIED infection rates
"Strategies to reduce perioperative infections can significantly improve outcomes," declares George Thomas, MD, an electrophysiologist with Weill Cornell Medical Center in New York.
Physicians who already use the Envelope have seen positive results within their practices. Dr. Ellis notes his practice has experienced a much lower infection rate in CIED patients. A study he co-authored, appearing in the journal Pacing and Clinical Electrophysiology in 2015, demonstrated the Envelope's effects. In the trial, there were zero CIED infections among patients who received an absorbable TYRX Envelope (0.0 percent infection rate) while infection was reported in 6 patients who did not receive a TYRX Envelope (4.8 percent).
Similar results have also been observed by Dr. Hanna. In his practice, CIED infections have been "significantly reduced" by the TYRX Envelope. In fact, even though infection rates in his practice were low to begin with, a greater than 50 percent decrease was achieved by using the Envelope.
"It's quite substantial," Dr. Hanna states. "I have felt a significant change and improvement, even though we're still treating the same population and doing the same types of procedures. It's been effective in my own institution."
As found in a number of clinical studies, patients treated with a TYRX Envelope experience 70 percent to 100 percent fewer infections compared to those without it. While smaller studies have proven the Envelope's effectiveness, more trials are on the way. For example, Dr. Ellis, as of mid-April 2016, has enrolled his first patients in a four-site randomized controlled trial. The objective is to determine whether the Envelope can "stand on its own legs" and still prevent infections even if clinicians skip a perioperative antibacterial pocket wash and send patients home without any oral antibiotics.
Now in progress: The first global, large-scale study in at-risk patients
On a larger scale, a major new RCT is now underway that may build on the positive results seen in the earlier, smaller-scale studies. This study, called WRAP-IT (The World-Wide Randomized Antibiotic Envelope Infection Prevention Clinical Study), is the first large-scale study of its kind to evaluate an antibacterial envelope in CIED patients at risk for infection. This ongoing CIED replacement complication study, which is currently evaluating the effectiveness of the Envelope in CIED patients and assessing related treatment costs, is concentrating on the two most common complications related to CIED implants: infection and lead system events.
The study will compare the rate of major CIED infections through 12 months after the device is implanted, between patients treated with and without the TYRX Envelope. Medtronic, the manufacturer of the TYRX Envelope, will utilize the results of this study to evaluate not only the outcomes achieved by the TYRX Envelope, but also to evaluate its effect on consequent healthcare cost.
In this study, up to 7,764 subjects are expected to be enrolled in up to 225 investigational sites worldwide, including the U.S., Canada, Europe, Middle East, greater China, New Zealand, Latin America, Singapore, Malaysia and India. The study was initiated in January 2015, with patients being followed for a minimum of 12 months.
Meeting the challenge with new technology
In a single-center, retrospective cohort study from the University of Pittsburgh Medical Center, the TYRX Envelope when used as a standard of care was associated with significantly lower rates of CIED infections. In a hypothetical projection, the use of the Envelope as a standard of care prevented 6.2 infections, equating to roughly $340,000 in avoided treatment costs.
While the rising incidence of CIED infection — and its associated higher treatment costs — has proven persistent, the technological advances of the TYRX Envelope offer the potential to protect CIED implants from the cost and complications of infections. As studies show, the sustained local delivery of antibiotics where needed most, may improve patient outcomes and reduce treatment costs.