Chemoprophylaxisand Preemptive Suppressive Therapy

It is sometimes assumed that what a drug can cure it will also prevent, but this is not necessarily so.

The basis of effective, true, chemoprophylaxis is the use of a drug in a healthy person to prevent infection by one organism of virtually uniform susceptibility, e.g. benzylpenicillin against a group A streptococcus. But the term chemoprophylaxis is commonly extended to include suppression of existing infection. To design effective chemoprophylaxis it is essential to know the organisms causing infection and their local resistance patterns, and the period of time the patient is at risk. A narrow-spectrum antibiotic regimen should be administered only during this period — ideally for a few minutes before until a few hours after the risk period. It can be seen that it is much easier to define chemotherapeutic regimens for short-term exposures (e.g. surgical operations) than it is for longer-term and less well defined risks. The main categories of chemoprophylaxis may be summarised as follows:

• True prevention of primary infection: rheumatic fever,8 recurrent urinary tract infection.

• Prevention of opportunistic infections, e.g. due to commensals getting into the wrong place (bacterial endocarditis after dentistry and peritonitis after bowel surgery). Note that these are both high-risk situations of short duration; prolonged administration of drugs before surgery would result in the areas concerned (mouth and bowel) being colonised by drug-resistant organisms with potentially disastrous results (see below). Immimocompromised patients can benefit from chemoprophylaxis, e.g. prophylaxis of Gramnegative septicaemia complicating neutropenia with an oral quinolone or of Pneumocystis carinii pneumonia with co-trimoxazole.

• Suppression of existing infection before it causes overt disease, e.g. tuberculosis, malaria, animal bites, trauma.

• Prevention of acute exacerbations of a chronic infection, e.g. bronchitis, in cystic fibrosis.

8 Rheumatic fever is caused by a large number of types of Group A streptococci and immunity is type-specific. Recurrent attacks are commonly due to infection with different strains of these, all of which are sensitive to penicillin and so chemoprophylaxis is effective. Acute glomerulonephritis is also due to group A streptococci. But only a few types cause it, so that natural immunity is more likely to protect and, in fact, second attacks are rare. Therefore, chemoprophylaxis is not used (see also p. 239).

• Prevention of spread amongst contacts (in epidemics and/or sporadic cases). Spread of influenza A can be partially prevented by amantadine; in an outbreak of meningococcal meningitis, or when there is a case in the family, rifampicin may be used; very young and fragile nonimmune child contacts of pertussis might benefit from erythromycin

Long-term prophylaxis of bacterial infection can be achieved often by doses that are inadequate for therapy, although prophylaxis of infection associated with surgical procedures should always employ high doses to ensure eradication of the high bacterial numbers that may be introduced to normally sterile sites. Details of the practice of chemoprophylaxis are given in the appropriate sections.

Attempts to use drugs routinely in groups specially at risk to prevent infection by a range of organisms, e.g. pneumonia in the unconscious or in patients with heart failure, in the newborn after prolonged labour, and in patients with long-term urinary catheters, have not only failed but have sometimes encouraged infections with less susceptible organisms. Attempts routinely to prevent bacterial infection secondary to virus infections, e.g. in respiratory tract infections, measles, have not been sufficiently successful to outweigh the disadvantages of drug allergy and infection with drug-resistant bacteria. In these situations it is generally better to be alert for complications and then to treat them vigorously, than to try to prevent them.

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