Fig. I I. I Efficacy of antimicrobials: examples of concentration-dependent and time-dependent killing (see text) (cfu = colony-forming units).

Remove barriers to cure, e.g. lack of free drainage of abscesses, obstruction in the urinary or respiratory tracts, infected intravenous catheters.

Decide whether chemotherapy is really necessary.

As a general rule, acute infections require chemotherapy whilst other measures may be more important for resolution of chronic infections. For example, chronic abscess or empyema respond poorly to antibiotics alone, although chemothera-peutic cover may be essential if surgery is undertaken in order to avoid a flare-up of infection or its dissemination during the breaking down of tissue barriers. Even some of the acute infections are better managed symptomatically than by antimicrobials; thus the risks of adverse drug reactions for previously healthy individuals may outweigh the modest clinical benefits that follow antibiotic therapy of salmonella gastroenteritis and streptococcal sore throat.

Select the best drug. This involves consideration of:

— specificity; ideally the antimicrobial activity of the drug should match that of the infecting organisms. Indiscriminate use of broad-spectrum drugs promotes antimicrobial resistance and encourages opportunistic infections (see p. 210). At the beginning of treatment, empirical 'best guess' chemotherapy of reasonably broad spectrum must often be given because of the absence of precise identification of the responsible microbe. The spectrum of cover should be narrowed once the causative organisms have been identified.

— pharmacokinetic factors; to ensure that the chosen drug is capable of reaching the site of infection in adequate amounts, e.g. by crossing the blood-brain barrier.

— the patient; who may previously have exhibited allergy to antimicrobials or whose routes of elimination may be impaired, e.g. by renal disease.

Administer the drug in optimum dose and frequency and by the most appropriate route(s). Inadequate dose may encourage the development of microbial resistance. In general, on grounds of practicability, intermittent dosing is preferred to continuous infusion. Plasma concentration monitoring can be performed to optimise therapy and reduce adverse drug reactions (e.g. aminoglycosides, vancomycin, 5-flucytosine).

Continue therapy until apparent cure has been achieved; most acute infections are treated for 5-10 days. There are many exceptions to this, such as typhoid fever, tuberculosis and infective endocarditis, in which relapse is possible long after apparent clinical cure and so the drugs are continued for a longer time, determined by comparative or observational trials. Otherwise, prolonged therapy is to be avoided because it increases costs and the risks of adverse drug reactions.

Test for cure. In some infections, microbiological proof of cure is desirable because disappearance of symptoms and signs occurs before the organisms are eradicated. This is generally restricted to especially susceptible hosts e.g. urinary tract infection in pregnancy. Microbiological culture must be done, of course, after withdrawal of chemotherapy.

Prophylactic chemotherapy for surgical and dental procedures should be of very limited duration, often only a single large dose being given. It should start at the time of surgery to reduce the risk of selecting resistant organisms prior to surgery (see p. 207).

Carriers of pathogenic or resistant organisms, in general, should not routinely be treated to remove the organisms for it may be better to allow natural re-establishment of a normal flora. The potential benefits of clearing carriage must be weighed carefully against the inevitable risks of adverse drug reactions.

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