Let’s start from the beginning: What is XABO and what is it used for, or rather what is it used against?

Lucas: One of the main complications after implantation of a shunt for hydrocephalus treatment is infection of the shunt after surgery. Infections happens when bacteria settle on the surface of the shunt system, where they cannot easily be attacked by the body’s immune defenses. Once bacteria have settled on an object foreign to the body, they can form a type of protective shield around themselves that cannot be easily penetrated by our immune system. To prevent such infections, it is helpful to equip a shunt so that it provides protection against infections. A great way to achieve this is with antibiotic-impregnated catheters. XABO is such a catheter. Catheters like XABO provide an opportunity to address this very critical complication and reduce the likeliness of it occurring.

Is there already scientific evidence for catheters of this type?

Lucas: Yes, there is! There are also several years of clinical experience with these types of catheters from other manufacturers. Antibiotic-impregnated catheters have demonstrated that they can significantly reduce the infection rate. This was achieved in a study called BASICS, which was conducted in England at various hospitals and was supervised by Dr. Conor Mallucci.

So, XABO is designed to fight bacteria and therefore infections. Does XABO work against all bacteria or only specific ones?

Tom: XABO contains the antibiotics rifampicin and clindamycin hydrochloride. These two antibiotics are primarily effective against gram-positive bacteria.

Gram-positive bacteria. What does that mean to a layperson?

Tom: Depending on their outer shell, bacteria can be divided into two types of structure. Bacteria can be stained using a staining technique known as Gram staining. Depending on whether they can be stained or not, they are referred to as gram-positive or gram-negative bacteria. This differentiation does not mean that some of them are more dangerous and the others less, it is only a form of clinical classification, which also influences how sensitive these bacteria are to certain antibiotics.

Lucas: It is known that the bacteria that cause most of the shunt infections are those that reside on the skin – Staphylococcus epidermis – and those in the air – Staphylococcus aureus. These two strains are responsible for over 60% of shunt infections. Both of them are gram-positive bacteria. Through contact with the surrounding air, skin or blood they can contaminate the sterile catheters and valves during the operation. Nonetheless, other bacteria can of course still play a role in the infection of implants such as hydrocephalus shunts. They include gram-negative bacteria such as the familiar E. coli. 

In other words: About 2/3 of shunt infections are caused by gram-positive bacteria, and the two antibiotics in XABO are effective against this proportion of bacteria?

Lucas: Yes, the majority of shunt infections are caused by gram-positive bacteria. Therefore, the two antibiotics in XABO are very useful because they are highly effective against the most relevant bacteria. They also use two different mechanisms of action against the same target organisms. The two antibiotics differ in how they work, but they attack the same bacteria. Consequently, they actually support each other. There are publications that show that these two antibiotics together even tend to have a synergistic effect. In this case, 1 plus 1 is a bit more than 2.

Tom: Another important effect is that the use of the two antibiotics prevents resistance. Resistance to rifampicin develops relatively quickly. Therefore, it is very important to have another antibiotic that fights the same bacteria and thus prevents resistance.

When did the idea first arise that MIETHKE also needed an antibiotic catheter? Why did we develop it?

Lucas: From a purely technical point of view: Reducing infection rates makes sense. No doubt about it. And it has been well established that systemic oral or intravenous antibiotic administration does not work sufficiently well if bacterial contamination happens during the surgery. If infection has occurred on an implant surface, there’s very little you can do systemically. It doesn’t matter if it’s a hydrocephalus shunt or a hip implant. The implant has to be removed because otherwise the infection cannot be treated. This has serious consequences for the patients, because ultimately an infection leads to a challenging revision.

Tom: ...and that’s not necessary. Revisions are necessary from time to time, but they should not be caused by infections.

Lucas: The treatment of such an infection is very costly. It is not uncommon for people to require intensive care treatment for a prolonged period of time until the infection has completely cleared up. A revision surgery can only take place after the infection is under control, but according to current studies this revision surgery is then associated with an increased risk of infection. And therein lies the motivation for such a catheter: To prevent infections and thus improve the quality of life of hydrocephalus patients.

That sounds logical. However, antibiotics are often viewed with some concern. What about the whole issue of antibiotic-resistant germs?

Lucas: The criticism of excessive use of antibiotics has been repeatedly reported by media outlets and it is certainly not unfounded. Just think of the reporting on the use of antibiotics in agriculture and the agricultural industry. Antibiotics are often administered and prescribed even though it doesn’t make any sense. However, this does not contradict the fact that it is essential for today’s medicine that antibiotics are available. They are the only reason why certain operations can be performed at all. This is because they kill bacteria in a targeted manner with very few side effects and are thus extremely useful. With XABO, the antibiotics are also contained in a very small quantity, much less than would be necessary for systemic administration; and they are administered exactly in the place where they are needed for infection prophylaxis: On the catheter surface. An extremely sensible use of antibiotics.

Does this antibiotic-impregnated catheter then replace systemic antibiotics, i.e. those given orally or by infusion?

Lucas: The answer is a resounding “yes and no”: Of course, systemic application makes sense, for systemic infections or where local applications are insufficient. On the other hand, systemic antibiotic administration is not effective against this specific problem of infection on implants. There are studies where antibiotics were administered for several days before implantation to reduce the number of bacteria beforehand. But even this has had no demonstrable effect on infection rates. It has also been clearly demonstrated that systemic administration alone does not help in the treatment of infections that already occurred. Intravenous or oral administration of antibiotics usually does not reach a sufficient concentration on the surface of the implants. Many antibiotics cannot even cross the blood-brain barrier and therefore cannot reach the area where the infection takes place in the case of ventricular catheters. In addition, the bacteria manage to take cover when an antibiotic arrives. Many can form a biofilm on the implant surface to protect themselves from antibiotics for a while. Just like they protect themselves from the immune response. 

So, what you are saying is that the bacteria sort of sit on the implant, build a little armor, a protective shield, around themselves with the biofilm, and then the body and the systemic antibiotic can’t do anything from the outside for a while.

Lucas: Exactly. This has been studied very well for various implants and even systemic antibiotics can’t do anything about it. That is why it makes sense to place the antibiotic in such a way that it can act in a targeted manner at the boundary layer between the implant and the surrounding tissue.

Could these infections be prevented in any other way?

Lucas: Again: Yes and no. You can significantly reduce the probability of a shunt infection through measures taken in the operating room. This has been shown in a number of publications. These measures include hygiene, preparation of the surgical site, the experience of the physician, and various procedures during the operation. There are many ways to influence the outcome. But these potential influences cannot reduce the risk to zero.

Tom: In numbers, this means that we currently find infection rates – with conventional shunts - ranging from 6–12%, in this order of magnitude. A clinic in the 6% infection rate range for conventional shunts is good and has probably already implemented many of the measures. But they can’t get any lower for a variety of reasons. This is where XABO can help, because it can lower the infection rates even further.

Are there patient groups for whom XABO is particularly suitable?

Lucas: I would start by saying: actually everyone. There are no exclusion criteria other than known allergies to the antibiotics. But apart from that, the product is proven to be safe and effective for infants, children, and adults. However, the most vulnerable group in terms of infections are newborn babies and children. That’s why I think an antibiotic-impregnated catheter is most relevant for this group of patients.

Thank you for all your answers. At the end, a personal question for you: XABO has accompanied you two for a longer, certainly in phases intensive, time. What is your best memory, your best moment?

Lucas: Oh, I think there were many. From the first working prototype to different stages of the approval process. The whole project had many positive moments.

Tom: I was mainly involved in the preparation for serial production. It was definitely a real challenge for us, because it’s a completely new process. And maybe that’s what makes it special now: To manage it with the team like this: Hats off and thanks to everyone who supported us!

Lucas: ...and for me, positive things just keep coming my way, because Tom writes emails like: “We´re ready: Serial production is starting!’ That’s cool!

Thank you for your time and good luck on the home stretch!