Hello and welcome to this session on treatment of chronic infections.

My name is Klaus Kirketerp-Møller and I am an orthopedic surgeon. In the field of orthopedic

surgery several chronic infections exits: Osteomyelitis, infection in bony tissue. Implant

related infections: Infection in arthroplasties, artificial joints. Infected osteosyntesis,

internally or externally fixated fractures and chronic wounds. Sometimes these infections

are combined, as a chronic wound is maintained by an infection in the deeper compartments

by an infected osteosytesis or osteomyelitis. Except from the chronic wound infections the

remaining infections mentioned are complicated by implant surfaces. Even chronic osteomyelitis

can be characterized as implant related as dead bony tissue serves as a foreign material.

As you have learned from the previous lessons we can be quite sure that chronic infections

are biofilm related and these orthopedic infections are no exception.

In theory the treatment of the foreign material related infections is straight forward: By

removal of the foreign body we will remove the bacterial biofilm and the immune defense

system together with antibiotics will take care of the planktonic bacteria. However there

are several issues that complicate matters since the foreign material has a supporting

function. In osteomyelitis removal of the infected bone will create a defect in the

bony structure and sometimes this defect is compromising stability and need to be replaced

and stabilized with new foreign material. In infected arthroplasties the arthroplasty

originally replaced a defect joint and simple removal will create significant morbidity

to the patient. In most cases these joints will be replaced again with new foreign material.

In infected osteosythesis, removal of the inserted material in some instances will cause

instability, an instability that in turn makes eradication of the infection more difficult.

I will not elaborate on the different protocols developed for these specific infections, time

and scope of this lecture does not permit that.

Bacteria in biofilm are extremely tolerant to antibiotics and the immune defense system.

How to deal with a situation where all defense systems are inefficient is still a challenge.

One strategy has been to remove all infected tissue surgically and in many cases this is

effective but not in all. Høgsberg et all published a paper in 2010 on chronic leg ulcers

treated with excision and split skin transplantation. This procedure includes deep revision of the

chronic wound tissue until apparently normal and non-infected tissue is reached. In cases

with presence of Pseudomonas aeruginosa before the procedure, only 33 per cent remained healed,

indicating that the bacteria resided deeper in the tissue. Strategies to deal with these

deeper residing microorganisms are still not clear. It is not only in chronic wounds that

the bacteria resides remote from the originally contaminated surface. In most cases of chronic

infections this could very well be one of the explanations for a relapse of infection

even after an initial successful treatment.

However the surgical procedure induces a change of milieu and this will force the microorganisms

to re-arrange and re-adapt. This might create a window of opportunity as described by Wolcott

et al. In the few hours following the surgical procedure antibiotics and the immune defense

system could prove to be effective. This could also explain why a chronic wound,

that have been present for months or even years, when treated with appropriate measures,

will start the healing process. We change the environment and the bacteria have to adapt

to that. When compression therapy is applied to a venous leg ulcer or proper off-loading

is provided to a diabetic foot ulcer, an ulcer, despite evidence of bacterial biofilm, can

heal.

I will postulate that challenging the bacteria with environmental changes is a very potent

treatment option that still needs exploring and development.

Antibiotic treatment is usually given systemically but the increased tolerance to antibiotics

in bacterial biofilm rise the problem that adequate tissue concentration of the antibiotic

is not possible. In order to overcome this problem local antibiotic treatment have been

developed. Different delivery systems are used, as simple flushing with antibiotics

seems to be inadequate. The antibiotic needs to be in a high concentration for some time,

even in antibiotics with concentration dependent kill-ratio. This is due to dilution by diffusion

and the fact that most antibiotics only kill bacteria in growth.

The ideal delivery system has not yet been identified but will have to deliver high concentrations

of antibiotics for a given time and the delivery should be complete. This is to ensure that

the period with sub-inhibitory concentrations is as short as possible to prevent resistance

due to a high selection pressure. Another option to give local treatment is

to use antiseptics. These substances can only be used locally but they too have the issue

with contact time. Tissue compatibility and toxicity is also a problem with some of these

and the fact that biofilm bacteria could reside far from the site of infection is still an

unsolved issue. Most local antiseptics unfortunately have either poor effect on biofilm or have

undesired toxic effect on the tissue. A promising, old but re-discovered agent is acetic acid.

This can be applied locally and act as an antiseptic. It has excellent anti-biofilm

activity, even on old experimental biofilm. We have published this anti biofilm property

of acetic acid but the clinical effect still needs to be proven in randomized clinical

trials. Combination of local antibiotic treatment

or antiseptics with systemically antibiotics is almost always necessary.

To summarize I would like to say that treating chronic infections in the orthopedic field

is not only a matter of bacterial biofilm and the tolerance to antibiotics but also

about preserving or restoring function. Strategies to accomplish this have been developed but

no one can guarantee eradication of the infection. Research in this area is more than welcome.

Thank you very much for your attention.

5.3 Treatment of Chronic infections by MD , Chief surgeon Klaus Kirketerp-Møller

细菌和慢性感染

与讲师见面