7: Antimicrobial chemotherapy

Chapter 7 Antimicrobial chemotherapy

Antimicrobial compounds include antibacterial, antiviral, antifungal and antiprotozoal agents. All of these, apart from the last group, are prescribed in dentistry.

All antimicrobials demonstrate selective toxicity; i.e. 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 all antimicrobials have adverse effects on humans and should therefore be used rationally and only when required.

Antimicrobial therapy aims to treat infection with a drug to which the causative organism is sensitive. Antimicrobials can be administered on a ‘best-guess’ basis, with a sound knowledge of the:

This is called empirical antibiotic therapy and contrasts with rational antibiotic therapy in which antibiotics are administered after the sensitivity of the pathogen has been established by culture and in vitro testing in the laboratory. In general, empirical therapy is undertaken in the majority of situations encountered in dentistry.

Bacteriostatic and bactericidal antimicrobial agents

Antimicrobial agents are classically divisible into two major groups: bactericidal agents, which kill bacteria; and 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 (e.g. erythromycin is bacteriostatic at low concentrations and bactericidal at high concentrations), the pathogen in question and the severity of infection. Further, host defence mechanisms play a major role in the eradication of pathogens from the body, and it is not essential to use bactericidal drugs to treat most infections. A bacteriostatic drug that arrests the multiplication of pathogens and so tips the balance in favour of the host defence mechanisms is satisfactory in many situations.

Principles of antimicrobial therapy

Antimicrobial agents should be prescribed on a rational clinical and microbiological basis. In general, therapy should be considered for patients when one or more of the following conditions are present:

(Note: this is not an exhaustive list.)

Spectrum of activity of antimicrobial agents

Antimicrobial agents can be categorized as broad-spectrum and narrow-spectrum antibiotics, depending on their activity against a range of Gram-positive and Gram-negative bacteria. For example, penicillin is a narrow-spectrum antibiotic with activity mainly against the Gram-positive bacteria, as is metronidazole, which acts almost entirely against strict anaerobes and some protozoa.

Broad-spectrum antimicrobials (e.g. tetracyclines, ampicillins) are active against many Gram-positive and Gram-negative bacteria, and they are often used for empirical or ‘blind’ treatment of infections when the likely causative pathogen is unknown. This unfortunately leads to ‘abuse’ of broad-spectrum agents, with the consequent emergence of resistance in organisms that were originally sensitive to the drug. The spectrum of activity of some broad-spectrum and narrow-spectrum antimicrobial agents is shown in Table 7.2.

Table 7.2 Spectrum of activity of some commonly used antimicrobial agents

Drug Spectrum
Phenoxymethylpenicillin (penicillin V) 1. Aerobic Gram-positives (e.g. streptococci, pneumococci, β-lactamase-negative)
  2. Anaerobic Gram-positives (e.g. anaerobic streptococci)
  3. Anaerobic Gram-negatives (e.g. most Bacteroides, fusobacteria, Veillonella)
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

Antimicrobial prophylaxis

Antimicrobial prophylaxis is 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:

When used appropriately, prophylaxis can reduce morbidity and the cost of medical care. Irrational prophylaxis leads to a false sense of security, increased treatment cost and the possible emergence of resistant flora.

Pharmacodynamics of antimicrobials

Drug interactions

Drug interactions are becoming increasingly common owing to the extensive use of a variety of drugs. For instance, antibiotics such as penicillin and erythromycin can significantly reduce the efficacy of some oral contraceptives, and antacids can interfere with the action of tetracyclines. All clinicians should therefore be aware of the drug interactions of any antimicrobial they prescribe. The major drug interactions of antimicrobials commonly used in dentistry are given in Table 7.3.

Table 7.3 Some drug interactions of antimicrobials commonly used in dentistry

Drug affected Drug interacting Effect
Penicillins Probenecid, neomycin May potentiate the effect of penicillin. Reduced absorption
Erythromycin Theophylline Increase theophylline levels, leading to potential toxicity
Cephalosporins Gentamicin Additive effect leading to nephrotoxicity
  Furosemide (Lasix) Possible increase in nephrotoxicity
Tetracycline Antacids, dairy products, oral iron, zinc sulphate Reduced absorption
Metronidazole Alcohol ‘Antabuse’ effect
  Disulfiram, phenobarbital, phenytoin Reduced effect

Failure of antimicrobial therapy

Consideration should be given to the following potential problems if an infection does not respond to drugs within 48 h:

Antibiotic resistance in bacteria

Emergence of drug resistance in bacteria is a major problem in antibiotic therapy and depends on the organism and the antibiotic concerned. Whereas some bacteria rapidly acquire resistance (e.g. Staphylococcus aureus), others rarely do so (e.g. Streptococcus pyogenes). Resistance to some antibiotics is virtually unknown (e.g. metronidazole), but strains resistant to others (e.g. penicillin) readily emerge.

Antibiotic resistance develops when progeny of resistant bacteria emerge. As they will be at a selective advantage over their sensitive counterparts, and as long as the original antibiotic is prescribed, the resistant strains can multiply uninhibitedly (e.g. hospital staphylococci with almost universal resistance to penicillin). Such antibiotic resistance can be divided into:

Mechanisms of antibiotic resistance (Table 7.4)

Inactivation of the drug

This is very common, e.g. production of β-lactamase by staphylococci. The enzyme, which is plasmid coded, destroys the β-lactam ring responsible for the antibacterial activity of penicillins.

Table 7.4 Plasmid-mediated antibiotic resistance

Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 7: Antimicrobial chemotherapy
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