Chapter 8 Antimicrobial prophylaxis
Antimicrobial agents are compounds which inhibit the growth, or kill microorganisms. Some of the early antimicrobial agents were derived from microorganisms and were called antibiotics. Nowadays antimicrobial agents are compounds which are synthesized to target certain specific functions in the microbial cell and are not derived from microorganisms; they are, therefore, not termed antibiotics but are referred to as antimicrobial agents.
Antimicrobial agents can be used for either treatment or prevention of infectious disease but must be used properly and accurately. The empirical overuse of antibiotics has been accompanied by an enormous increase in the emergence of microbial resistance; this has made some antimicrobials useless for the treatment of some common diseases. The use of antimicrobials in the prevention of disease is called prophylaxis and is controversial. In many cases the use of prophylactic antimicrobials in oral surgery is a matter of clinical habit rather than based on sound evidence-based clinical science. There are four occasions when prophylactic antimicrobials are indicated and these are:
The majority of post-operative infections occur at the time of surgery. Secondary infection can occur following surgery (e.g. if a wound is disturbed or sutures are lost), but this is not usual. In a series of animal experiments in the 1960s it was demonstrated that post-operative infections are usually infected at the time of surgery. The source of the post-operative infection can either be endogenous or exogenous. Endogenous infections are derived from the patient’s own microflora and are introduced at the time of the operation; they then proliferate and an infection results. The commonest time when endogenous post-operative infection occurs is when the surgery is done on a site already infected with the person’s own microflora. Ideally surgery should not be done on areas that are not infected, but this is not always possible. Exogenous wound infections arise from microorganisms being introduced into the mouth from a source outside the oral cavity, and are usually caused by poor aseptic technique or by non-sterile instruments. Exogenous wound infections can often be prevented by careful preparation of the operation site with judicious use of antiseptics.
There are two types of post-operative infection: immediate or late. Immediate post-operative infections occur in the first 2–3 days following the operation. Late infections can occur weeks or months after the operation and are due to microorganisms remaining quiescent within the site and then being reactivated. Late infections of this kind are particularly associated with implants or surgically-placed prostheses and are often called latent infections.
The mechanism of antimicrobial prophylaxis is still controversial. Most antimicrobial agents work best on actively dividing microorganisms which does not usually apply to most immediate wound infections. Successful antimicrobial prophylaxis does appear to suppress microbial growth. A number of other mechanisms could explain how prophylactic antimicrobials work and include:
The above explanations all have some experimental evidence to support them, but it is all derived from in vitro experiments. The lack of any direct experimental evidence of the mechanism has led many people to question whether antimicrobial prophylaxis is necessary at all, especially with oral surgical operations where the incidence of post-operative infection is very low.
Despite the evidence that infection occurs at the time of operation many clinicians still give courses of antimicrobial prophylaxis at times that are inappropriate and will miss the critical time when antimicrobial protection is required. For example, a common time to give antimicrobials is if an extraction cannot be achieved by simple forceps action and a surgical operation is necessary. Often it is many hours after the operation by the time the antimicrobials are dispensed. All the available clinical evidence has shown that giving antimicrobials some time after the operation has no effect on the outcome. There are now a large number of double-blind clinical trials that have shown that only an antimicrobial given before the operation, in sufficient time for serum and tissue concentrations to be maximal, will have a prophylactic effect on post-surgical infection.
One important factor to consider when selecting the antimicrobial agent is that it should be able to penetrate the tissues concerned and in particular bone. Clindamycin, the cephalosporins and metronidazole all penetrate bone well, but amoxicillin does not and is not licensed for use in this tissue.
The macrolides also do not have good bone penetration. Amoxicillin is by far the most commonly given prophylactic antimicrobial and to reach appropriate prophylactic concentrations in bone, for example, it is nec/>