Infection prevention for vascular catheters

It is well known that the resistance to antibiotics of healthcare-associated infections (HCAIs) is caused by the long-term misuse of antimicrobial agents in hospitals. Furthermore, there is no single intervention that will eradicate these infections. However, it has been discovered that tackling the source of the infection can achieve significant progress in lowering infection rates.

Bloodstream infections are commonly caused by bacteria colonising the surface of a vascular catheter or feeding line. In fact, more than 6,000 people in the UK contract bloodstream infections caused by feeding lines and vascular catheters every year. Healthcare professionals often have to resort to administering broad-spectrum systemic antibiotics to treat the infection. Although in most cases this eliminates the infection, it should not be regarded as a success because it can encourage the development of further infection by antibiotic-resistant strains.

As practioners for several years of infectious disease medicine and internal medicine in Houston, Texas, Dr Issam Raad** and I found that vascular catheter infections were becoming more prevalent and we wanted to find an effective solution to prevent them.

Our aim was to develop a tool to prevent an infection before it entered the bloodstream, thus reducing the need for a reactive approach with systemic antibiotics. We developed the Cook Spectrum Mino-cycline/Rifampin Impregnated Catheter as a new anti-infective central venous catheter that would give patients the best possible protection against infection — something that traditional catheters simply cannot offer.

In the initial development, we wanted to address issues related to catheter insertion and maintenance, such as:

• The unacceptably high rate of catheter-associated bloodstream infection, which stood at over 5% at that time;
• The 5-10% of morbidity and mortality at that time – another unacceptable figure;
• The difficulty of catheter management, including the removal of catheters, indwelling times, etc, and
• The soaring economic impacts of HCAIs, including the increased hospital stay and recovery time and the treatment costs of preventable catheter-related bloodstream infections, (CRBSIs) ­– something that had previously not been taken into consideration.

It was essential, as a next step, to choose a suitable coating or impregnation for the catheter. It was clear that antimicrobial agents that can combat bloodstream infections, including gram-positive, gram-negative and fungal organisms, should be used. Any antimicrobial agent also needed activity against the whole spectrum of bacteria, to provide the best protection possible. Vancomycin, for example, was not deemed suitable as it is active only against gram-positive organisms and its use has already been proven to result in other infections.

Antimicrobial durability was also vital, so we had to choose antibiotics that were most likely to adhere, which was also dependent on the catheter material. The ideal choice was a catheter impregnated with rifampin and minocycline. Impregnation of the catheter material ensures the antimicrobial combination is present on both the inner and outer surfaces of the catheter.

Bacteria are often the catalyst for HCAIs. But because minocycline and rifampin employ different mechanisms of action, the bacteria would need to develop resistance to both antibioticsto make the combination ineffective. According to reports, resistance emerges only when there is a low level of antibiotic in the presence of a high concentration of bacteria – this impregnated catheter reverses the antibiotic/bacteria ratio, and almost negates worries about resistance.

Furthermore, each antibiotic chosen for the new catheter has its own way of working. On the one hand, rifampin inhibits the DNA-dependent components of cells by binding its beta subunit, thus preventing it from transcribing to ribonucleic acid (RNA) and subsequent translation to proteins. Minocycline, on the other hand, is a member of the broad spectrum tetracycline group of antibiotics and interferes with the ability of bacteria to produce proteins that are essential to their survival.

The use of minocycline and rifampin synergistically in the treatment of HCAIs is new. More often rifampin is used for treating the meningitis form of tuberculosis and minocycline is mainly prescribed for treating acne and other skin diseases as well as Lyme disease. However, the emergence of organisms that are resistant to vancomycin – an antibiotic that was previously used in the treatment of infections – has seen the need for a different drug combination.

Minocycline and rifampin have been used as systemic antibiotics for several decades and their proven effectiveness is well suited for the prevention of bloodstream infections. Clinical evidence also indicates that a decrease in the use of systemic antibiotics, such as vancomycin, can reduce both cost and the likelihood of resistance.1

When designing the catheter, our first goal was to prevent bloodstream infections. By providing antibiotic coverage on both the external and internal surfaces of the catheter, minocycline and rifampin are particularly effective in reducing the rate of catheter colonisation and catheter-related bloodstream infection.

Catheters are particularly important devices in critical care medicine, as they are commonly used in patients in high dependency units who are at particular risk of contracting infections. Doctors regularly place catheters into large veins in the neck, chest or groin when the patient is in need of regular fluids or drugs.

Only a few steps are needed to ensure the correct use of catheters in the fight against catheter-related blood stream infections. They are:

• Using clinical safety data to determine the appropriate indwelling time for these catheters, and
• Employing best practice barrier techniques and other hygiene measures when inserting catheters.

The aim for the future is that the current short-term (30 day) use of this catheter is extended for long-term use. While short-term catheters needed a material that would stay in the body for only a short period of time, long-term catheters will need to utilise a material that is biocompatible with longer insertion durations.

Our greatest hope is that as a result of this catheter development work, there will be 6,000 fewer residents and catheter users in the UK with healthcare-acquired infections in future.