Choice

The general rule is that selection of antimicrobials should be based on identification of the microbe and sensitivity tests. All appropriate specimens (blood, pus, urine, sputum, cerebrospinal fluid) must therefore be taken for examination before administering any antimicrobial.

This process inevitably takes time and therapy at least of the more serious infections must usually be started on the basis of the 'best guess'. With the worldwide rise in prevalence of multiply-resistant bacteria during the past decade, knowledge of local antimicrobial resistance rates is an essential prerequisite to guide the choice of local 'best guess' (or 'empirical') antimicrobial therapy. Publication of these rates (and corresponding guidelines for choice of empirical antibiotic therapy for common infections) is now an important role for clinical diagnostic microbiology laboratories. Such guidelines must be reviewed regularly to keep pace with changing resistance rates.

USE OF ANTIMICROBIAL DRUGS j |

When considering 'best guess' therapy, infections may be categorised as those in which:

1. Choice of antimicrobial follows automatically from the clinical diagnosis because the causative organism is always the same, and is virtually always sensitive to the same drug, e.g. meningococcal septicaemia (benzylpenicillin), some haemolytic streptococcal infections, e.g. scarlet fever, erysipelas (benzylpenicillin), typhus (tetracycline), leprosy (dapsone with rifampicin).

2. The infecting organism is identified by the clinical diagnosis, but no safe assumption can be made as to its sensitivity to any one antimicrobial, e.g. tuberculosis.

3. The infecting organism is not identified by the clinical diagnosis, e.g. in urinary tract infection or abdominal surgical wound infection.

In the second and third categories particularly, choice of an antimicrobial may be guided by:

Knowledge of the likely pathogens (and their current local susceptibility rates to antimicrobials) in the clinical situation. Thus cephalexin may be a reasonable first choice for lower urinary tract infection (coliform organisms — depending on the prevalence of resistance locally), and benzylpenicillin for meningitis in the adult (meningococcal or pneumococcal).

Rapid diagnostic tests. Use of tests of this type is about to undergo a revolution with the widespread introduction of affordable, sensitive and specific nucleic acid detection assays (especially those based on the Polymerase Chain Reaction, PCR). Classically, antimicrobials were selected in the knowledge that the organism was a Gram-positive or Gramnegative coccus or bacillus, observed by direct staining of body secretions or tissues. It is necessary to know the current local sensitivities to antimicrobial drugs for organisms so classified. Thus flucloxacillin may be indicated when clusters of Gram-positive cocci are found (indicating staphylococci), but vancomycin is preferred in many hospitals with a high prevalence of methicillin-resistant Staphylococcus aureus (MRSA). The use of Ziehl-Neelsen staining may reveal acid-fast tubercle bacilli. Light microscopy will remain useful in this way for many years to come, but use of PCR to detect DNA sequences specific for individual microbial species or resistance mechanisms greatly speeds up the institution of definitive, reliable therapy. These methods are already widely used for diagnosing meningitis (detecting Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae) and tuberculosis (including detection of rifampicin resistance).

Modification of treatment can be made later if necessary, in the light of culture and sensitivity tests. Treatment otherwise should be changed only after adequate trial, usually 2-3 days, for over-hasty alterations cause confusion and encourage the emergence of resistant organisms.

Route of administration. Parenteral therapy (which may be i.m. or i.v.) is preferred for therapy of serious infections because high therapeutic concentrations are achieved reliably and rapidly. Initial parenteral therapy should be switched to the oral route whenever possible once the patient has improved clinically and as long as they are able to absorb the drug i.e. not with vomiting, ileus or diarrhoea. Many antibiotics are, however, well absorbed orally, and the long-held assumption that prolonged parenteral therapy is necessary for adequate therapy of serious infections (such as osteomyelitis) is often not supported by the results of clinical trials.

Although i.v. therapy is usually restricted to hospital patients, continuation parenteral therapy of certain infections, e.g. cellulitis, in patients in the community is sometimes performed by specially-trained nurses. The costs of hospital stays are avoided, but this type of management is suitable only when the patient's clinical state is stable and oral therapy is not suitable.

Oral therapy of infections is usually cheaper and avoids the risks associated with maintenance of intravenous access; on the other hand, it may expose the gastrointestinal tract to higher local concentrations of antibiotic with consequently greater risks of antibiotic-associated diarrhoea. Some antimicrobial agents are available only for topical use to skin, anterior nares, eye or mouth; in general it is better to avoid antibiotics that are also used for systemic therapy because topical use may be especially likely to select for resistant strains. Topical therapy to the conjunctival sac is used for therapy of infections of the conjunctiva and the anterior chamber of the eye.

Other routes used for antibiotics on occasion include inhalational, rectal (as suppositories), intra-ophthalmic, intrathecal (to the CSF), and by direct injection or infusion to infected tissues.

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