The choice of effective chemotherapy involves the nature and site of the infection, the known or suspected causative organism, the characteristics of the patient, the available antibiotics, their pharmacokinetic profiles and their cost.
The nature and site of the infection
When the nature of the infection (and the likely causative organism) can be predicted from the clinical features of the illness, treatment can proceed without isolation of the causative organism, as in the prescription of penicillin for acute follicular tonsillitis or lobar pneumonia. In exacerbations of chronic bronchitis the causative organisms are almost always pneumococci and H. influenzae, and ampicillin or co-trimoxazole is, therefore, indicated without specific laboratory diagnosis.
If the patient is seriously ill, antibiotic therapy must be started on a 'best guess (empirical) basis. The presentation of the illness may assist in the selection of the most appropriate agent. If there are no clues as to the nature of the infection, treatment should be started with a combination of antibiotics such as gentamicin plus a penicillin, or with a cephalosporin such as cefotaxime.
The known or suspected causative organism
When there is uncertainty about the nature of the infection a bacteriological diagnosis should be made, whenever possible , so that the appropriate antibiotic can be given. If the organism is one such as Streptococcus pyogenes, which has a predictable susceptibility to the generally used antimicrobial agents, it is still wise to obtain an antibiotic sensitivity profile in view of emerging resistance.
Sensitivity tests will be required for bacteria known to vary in their susceptibility to antimicrobial agents (an increasing problem). The acquisition of resistance occurs particularly with staphylococci, Gram-negative bacilli and mycobacteria. Once the sensitivity of the organism has been determined, it is relatively rare for this to change during the course of treatment.
The age and sex of the patient, together with a knowledge of previous adverse reactions, and immune, renal and liver function must all be considered before a final selection of the antibiotic or antibiotics is made.
Children and pregnant women should not be given to tetracyclines or 4-quinolones. Co-trimoxazole is also best avoided in pregnancy and the elderly, and this compound, together with other sulphonamides, must not be given patients with glucose-6-phosphate dehydrogenase deficiency as haemolysis may be precipitated. Chloramphenicol should be prescribed only in the circumstances and is contraindicated in the neonate. Ampicillin must not be given to patients suffering from infectious mononucleosis and the aminoglycoside antibiotics should be used with caution in patients with renal disease and in the elderly. Clindamycin should not be used for trivial infection because of the risk of colitis.
The available antibiotics
Having considered the above factors, the clinician selects an appropriate antibiotic with reference to its microbiological and pharmacological properties, adverse reactions and cost. The British National Formulary published in the UK is a valuable guide.
More than one antibiotic (but rarely more than two) may be required for the initial treatment of septicaemia or for serious infections in the immunosuppressed. The use of two or more antibacterial drugs is only occasionally of proven value in other than the seriously ill. Thus, in tuberculosis, three agents are prescribed, at least initially, to reduce the emergence of resistant strains. Two drugs with different modes of action may also be used when it has been shown that the combination is synergistic.
Antimicrobial agents are often very expensive. In general, new agents are more expensive than older compounds, while parenteral preparations are always much more costly than the oral formulation. Unusual or new antibiotics should not be prescribed without good reason as the difference in cost compared with other agents can be over a hundred-fold. Particularly expensive agents include vancomycin, imipenem, the newer cephalosporins, aciclovir, zidovudine and the liposomal formulation of amphotericin.