Antimicrobial agents include antibacterial, antiviral, antifungal and antiprotozoal agents. Apart from the last group, dental practitioners are frequently called upon to prescribe these drugs and therefore should be conversant with the mode of action, spectrum of activity, side-effects and contraindications of at least the major groups of antimicrobials. This chapter summarizes the principles of antimicrobial therapy together with notes about the nature and use of antimicrobials frequently prescribed in dentistry.All antimicrobials demonstrate selective toxicity, in that the drug can be administered to humans with reasonable safety while having a marked lethal or toxic effect on specific microbes. The corollary of this is that to some extent all antimicrobials have adverse effects on humans and should therefore be used rationally and only when required.
Antimicrobial agents are classically divisible into two major groups as bactericidal agents which kill bacteria or bacteriostatic agents which inhibit multiplication without actually killing the pathogen. However, the distinction is rather hazy and is dependent on factors such as the concentration of the drug and the organism concerned and severity of infection. For instance, it is known that erythromycin is bacteriostatic at low concentrations and bactericidal at high concentrations.
Further, it is important to realize that host defence mechanisms play a major role in eradication of microbial pathogens from the body and it is not essential to use bactericidal drugs to treat most infections. A bacteriostatic drug which arrests the multiplication of pathogens and so tips the balance in favour of the host defence mechanisms is satisfactory in many situations.
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
|Cell wall||β-Lactams, e.g.penicillin, ampicillin, cephalosporin, cloxacillin||Cidal||Interfere with crosslinking of cell wall peptidoglycan molecules|
|Ribosomes||Erythromycin Fusidic acid (topical)||Statica or Cidalb||Interfere with translocation, thus inhibiting protein synthesis|
|Tetracycline||Static||Interferes with attachment of transfer RNA thus inhibiting protein synthesis|
|Cytomplasmic membrane||Polyenes, e.g. nystatin, amphotericin||Static||Disrupts yeast cell membrane|
|Nucleic acid replication||Metronidazole||Cidal||Interferes with DNA replication|
|Acyclovir||DNA synthesis in DNA viruses|
Antimicrobial agents should be prescribed on a rational clinical and a microbiological basis. In general, therapy should be considered for patients with orofacial infections when one or more of the following conditions are present: (1) patients with fever who may complain of malaise, fatigue, dizziness and weakness; (2) spreading infection without localization; (3) chronic infection despite drainage or débridement; (4) medically compromised patients; and (5) cases of osteomyelitis, bacterial sialadenitis and acute ulcerative gingivitis.
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.
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.
Whenever possible, a single antimicrobial agent should be used to reduce the incidence of possible side-effects, the emergence of resistant bacteria, and drug costs. However, there are certain clinical situations where a combination of drugs is valuable, e.g. the necessity of achieving a high bactericidal level when treating patients with infective endocarditis. Other examples include the use of gentamicin and metronidazole in the empirical treatment of a patient with serious abdominal sepsis, and combined drug therapy in the management of tuberculosis.
Antimicrobial prophylaxis has been defined as the use of a drug to prevent colonization or multiplication of microorganisms in a susceptible host. The value of prophylaxis depends upon a balance between the benefit of reducing the infection risk and consequent secondary morbidity against the possible toxic effects to the host, alteration of the host commensal flora, the emergence of resistant bacteria and cost. When used rationally, prophylaxis can reduce morbidity and the cost of medical care although when used inappropriately a false sense of security with increased costs is likely to result.
The functions of antimicrobial prophylaxis are: (1) to prevent the colonization of the host by a small number of virulent agents; or (2) to prevent implanted organisms reaching a critical mass sufficient to produce infection; or (3) to prevent the emergence of latent infection.
In dentistry, antibiotics are used as prophylactic agents in a number of situations, although in some instances their use is highly controversial as the efficacy of prophylaxis has not been proven scientifically.
Prophylactic antimicrobial agents are definitely indicated during dental treatment involving patients with at risk status with respect to infective endocarditis (see Chapter 12), facial fractures or compound skull fractures, and cerebral rhinorrhoea. Oral surgery performed in immunocompromised patients, or in patients who have recently received radiotherapy to the jaws, may also require prophylaxis. In the former situation the patients are susceptible to infection due to generalized immunodeficiency while in the latter instance the jaws succumb to infection due to severe ischaemia of the bone consequential to radiotherapy.
Prophylactic antimicrobial agents may possibly be required in patients with prosthetic hip replacements and ventriculoatrial shunts. Consideration should also be given to prophylactic drugs during insertion of implants or bone grafting. However, the advantages and disadvantages of antimicrobial therapy in such instances should be carefully weighed in each individual case. The routine administration of antimicrobial agents after uncomplicated third molar surgery is often given but is probably unnecessary.
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.
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.