- Hello, dear colleagues, I'm Dan Atar, Professor of Cardiology at the Oslo University Hospital, and I welcome you to the third podcast of the "Cardiac Implantable Electronic Devices," CIED infection series. I invited Stefan Hagel, Infectious Diseases Specialist at the Jena University Hospital in Germany to discuss why antibiotics alone often fail to treat CIED infections.

- Hello, Dan. Thank you very much for the invitation, and greetings from Germany.

- So the topic is clear, CIEDs is implantable cardiac devices, but in fact, probably, implants, in general, can get infected. Why is this? What is causing this?

- You're completely right. Whenever there is foreign material in your body, there is an increased risk of an implant-associated infection. And the main reason for this phenomenon is that bacteria love to stick on the surface of the implants. And there are very nice animal studies showing that less than 100 bacteria are sufficient to make an implant-associated infection, compared to over 1 million bacteria necessary for infection without implants. And interestingly, there is a theory, it's called the race for the surface, and it says that a presence of a foreign body triggers a race between the bacteria on the one side, and on the other hand, the host cells for colonisation of the surface. And when the bacteria are faster than the host cells, they produce a biofilm and make an infection. And if the host cells are faster, there will be no infection.

- That is extremely interesting and so intriguing. I didn't know that 100 bacteria should be enough, but obviously, this is really a problem. So are CIED infections always visible?

- No, and this is the very, very big problem in daily care. We have the very easy cases, patients are presenting with a hot, swollen, warm pocket, and this makes it very easy. This is like straightforward diagnosis of a pocket infection. And these are approximately two thirds of all CIED infections, like it was shown in the ELECTRa Registry. And on the other hand, you have the very difficult cases, patients presenting with a positive blood culture, signs of infection, fever, maybe weight loss, but no local signs of a pocket infection. And this is where we have to really work like a detective to find the reason for this.

- So this is really speaking to my imagination. We are entering Sherlock Holmes topic now. Tell me more.

- Like, if you look at a patient with staph aureus bacteremia or also coagulase-negative staphylococci in more than one blood culture, or patients with infection where a septic embolic event was the major factor, for example, vertebral osteomyelitis, a TEE, a transesophageal echocardiography, must always be carried out to exclude a CIED lead infection. So even if the pocket doesn't show any signs of infection, it can be that the lead is infected and can seed some septic emboli. So this is very important, and in most of the cases, it's staphylococci. But also, if you have a recurrent bacteremia bloodstream infection with a gram-negative pathogen or with other gram-positive pathogens, and you do not find proper reason for the bacteremia, you always have to look for a possible CIED infection. For example, if you have a patient with a staph aureus bacteremia, he has a risk of 30% that the CIED will be infected in a later stage, maybe two weeks, three weeks, or four weeks after the initial event.

- That is amazing. And you know, what you are telling us is in many ways reminiscent of what we experience in our field in cardiology regarding endocarditis, and particularly endocarditis with artificial valves. You have the same elements. You have often a dental infection. You have the need for transesophageal echo, and you have very severe bacteremia. So I see a certain parallel there. But of course, with the lead infections, that's really difficult to capture. Why are antibiotics not effective?

- Here we have the major problem that bacteria can form a biofilm. And this is, like, where first, they attach to the surface, and within a few days, they produce a biofilm, and the biofilm is like a structure of different compounds, bacteria, DNA, proteins, polysaccharides. And within this biofilm, interestingly, some of the bacteria, they feel in a kind of winter sleep hibernation, and they can hide under the dead bacteria, and they can escape the immune system. So this is one problem. They can escape the host cells, and in addition, we cannot kill these dormant bacteria with our normal antibiotics, with the beta-lactam antibiotics. And this is the big problem, and the consequences that we have a recurrence rate of 50 to 100% if we do not make an extraction of all the foreign devices. And the risk of 30 day, mortality is seven times higher if you do not perform extraction of the device.

- And of course, we are talking about a life-threatening situation. I mean, waiting with this situation in a patient will deteriorate the prognosis for sure. So what is the right treatment if antibiotics alone are not effective?

- Really the key point is extraction of the complete device. This is, like, if you do not have a foreign material, a foreign device in your body, you do not have the problem of the biofilm. And this is very clearly stated in the EHRA consensus document, and here it says the key aspect to successful treatment for definite CIED infection is complete removal of all parts of the system and the transvenous hardware, including device and all the leads. So this is really the major point, and you can treat a patient two weeks, four weeks with antibiotics, and you will not get rid of this biofilm, and you will get the recurrence maybe half a year later, several months later. This is the major problem. And the sooner you do the extraction, the better it is for the patient, as you just said.

- I absolutely agree. Thank you very much. I mean, your insights are incredibly important, and you clearly explain that there are two types of infections, a localised one and a systemic one. Antibiotics are often ineffective against infections when there is a device involved. And the only right solution for many, if not most patients, is extraction. So if you want to learn more about lead extraction, there will be an upcoming podcast number four which will deal specifically with this, and there is also an interesting website, deviceinfection.com. I'd like to thank Stefan Hagel for these very interesting insights that you shared with us, and I hope to see the audience again in the next podcast.

- Thank you very much.