Mode of action of antimicrobial agents

Antimicrobial agents inhibit the growth of or kill microorganisms by a variety of mechanisms. In general, however, one or more of the following four specific target sites are involved: (1) the cell wall, (2) the cytoplasmic membrane, (3) ribosomes, and (4) nucleic acid replication sites. The detailed modes of action of antimicrobials are outside the scope of this book and the reader is referred to texts in the reading list for this information. A summary of the mode of action of commonly used antimicrobials in dentistry is given in Table 14.1

The choice of drug

The choice of drug is strictly dependent upon the nature of the infecting organism(s) and their sensitivity pattern(s). However, in a clinical emergency such as septicaemia or Ludwig’s angina, antimicrobial agents must be prescribed empirically until laboratory tests have been completed. In other conditions such as acute ulcerative gingivitis where a Gram-stained smear of the lesion is diagnostic, therapy with metronidazole should be instituted without further laboratory tests since it is extremely difficult to isolate and identify spirochaetes (see Chapter 5). In general another antimicrobial should be prescribed if the patient has had penicillin within the previous month. This is because of the natural selection and persistence of resistant bacterial populations when they are exposed to the drug.

Spectrum of activity of antimicrobial agents

Antimicrobial agents can be categorized into broad-spectrum and narrow-spectrum drugs depending on their activity against a range of Gram-positive and Gram-negative bacteria. Penicillin is a good example of a narrow-spectrum antibiotic with activity mainly against the Gram-positive bacteria. Similarly, metronidazole is a recent example of a narrow-spectrum drug which acts almost entirely against strict anaerobes and some protozoa.

On the other hand, broad-spectrum antimicrobial agents are active against many Gram-positive and Gram-negative bacteria; examples include tetracyclines, ampicillins and cephalosporins. Hence the broad-spectrum agents are often used for the blind or empirical treatment of infections when the likely causative pathogen is unknown. This, unfortunately, leads to abuse of broad-spectrum agents with consequential emergence of resistant organisms which were originally sensitive to the drug. The spectra of activity of some broad- and narrow-spectrum antimicrobial agents used in dentistry are shown in Table 14.2.

Penicillinase-resistant penicillins (e.g. flucloxacillin) All the above, including β-lactamase-producing staphylococci Ampicillin As for penicillin, also includes Haemophilus spp. Cephalosporins As for penicillin, also includes some coliforms Erythromycin Gram-positives mainly but some anaerobes not susceptible at levels obtained by oral administration Tetracycline Broad spectrum. Many Gram-positives and negatives Metronidazole All strict anaerobes are sensitive, including some protozoa. Of questionable value for facultative anaerobes

Is there an infective aetiology?

When there is no good clinical evidence of infection antimicrobial agents are rarely necessary, except in prophylaxis which is discussed above.

Have relevant specimens been taken before treatment?

As explained in Chapter 13, appropriate specimens should be collected before drug therapy is started as the population of pathogens may be reduced, and therefore less easily isolated, if specimens are collected after antimicrobial agents have been taken. Further, the earlier the specimens are taken, the more chance that the results will be available to help with patient management.

Timing the start of treatment

In patients with life threatening infections e.g. Ludwig’s angina, often intravenous therapy should be instituted immediately after specimen collection. Antimicrobial therapy may be withheld in chronic infections such as angular cheilitis until laboratory results are available.