Chapter 7 Antimicrobial chemotherapy
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.
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.
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.
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:
The choice of drug is strictly dependent upon the nature of the infecting organisms and their sensitivity patterns. However, in a clinical emergency such as septicaemia or Ludwig’s angina, antimicrobial agents must be prescribed empirically until laboratory tests are completed. In general, another antimicrobial drug should be prescribed if the patient has had penicillin within the previous month because of the possible presence of penicillin-resistant bacterial populations previously exposed to the drug.
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.
|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|
However, there are certain clinical situations where a combination of drugs is valuable: for example, to achieve a high bactericidal level when treating patients with infective endocarditis; the use of gentamicin and metronidazole in the empirical treatment of a patient with serious abdominal sepsis; and combination therapy in the management of tuberculosis. In dentistry, combination therapy should be avoided as far as possible.
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.
Appropriate specimens should be collected before drug therapy is begun 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 likely it is that the results will be useful for patient management.
In patients with life-threatening infections, e.g. Ludwig’s angina, intravenous therapy should generally be instituted immediately after specimen collection. Antimicrobial therapy may be withheld in chronic infections until laboratory results are available (e.g. actinomycosis).
Consider the pharmacodynamic effects, including toxicity, when choosing a drug from a number of similar antimicrobial agents that are available to treat many infections (see below). An adequate medical history, especially in relation to past allergies and toxic effects, should be taken before deciding on therapy.
Ideally, treatment should continue for long enough to eliminate all or nearly all of the pathogens, as the remainder will, in most instances, be destroyed by the host defences. Conventionally, this cannot be precisely timed, and standard regimens last for some 3–5 days, depending on the drug. However, a short-course, high-dose therapy of certain antibiotics such as amoxicillin is as effective as a conventional 5-day course. The other advantages of short courses of antimicrobial agents are good patient compliance and minimal disturbance to commensal flora, leading to an associated reduction in side effects such as diarrhoea.
The drug must reach adequate concentrations at the infective focus. Some antibiotics, such as clindamycin, that penetrate well into bone are preferred in chronic bone infections; in meningitis, a drug that penetrates the cerebrospinal fluid should be given.
The pathway of excretion of an antimicrobial agent should be noted. For example, drugs metabolized in the liver, such as erythromycin estolate, should not be given to patients with a history of liver disease because they may cause hepatotoxicity, leading to jaundice.
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.
|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|
|Disulfiram, phenobarbital, phenytoin||Reduced effect|
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: