The treatment of tuberculosis in childhood.

992 The treatment of tuberculosis (TB) in children and adults has remained unchanged for more than 30 years, and although new drugs are at last entering clinical trials it will be 5-10 years before their precise place in therapy is established. It is therefore necessary to continue to use our current drugs with care and prudence and be particularly careful about preventing the further development of drug resistance. The principles of treatment in adults and children are the same, but there is an increasing appreciation that the spectrum of disease seen in childhood is different and that children also differ from adults with regard to the pharmacokinetics of drugs. Several populations of mycobacteria can be identified within TB lesions. 1 Within the walls of cavities there is a large population of actively multiplying organisms. A typical cavity might contain 10 8 bacilli, and this large population increases the probability that mutations will occur that select for drug resistance. Smaller populations of progressively less active or dormant organisms will be found in caseation tissue and within macrophages. Killing the metabolically active organisms is a relatively easy task, and isoniazid (INH) is responsible for the death of 90% of these bacilli within 48 hours. The elimination of the intermittently active or dormant organisms is more difficult and it is failure to sterilise lesions by killing these persistent bacilli that leads to relapse. Drugs that rapidly eliminate the great bulk of metabolically active bacilli are termed bactericidal drugs, and the most active bactericidal agent is INH, with rifampicin (RMP) being about half as active in this respect. 2 Drugs that eliminate persisting intermittently active or dormant bacilli are termed sterilising agents, the most important being RMP and pyrazinamide (PZA); without them 6-month short-course treatment is not possible. INH will also ultimately sterilise lesions but this requires at least a year of treatment. Five drugs, INH, RMP, PZA, ethambutol (EMB) and streptomycin (SM), are regarded as essential agents by the World Health Organization (WHO). 3 RMP, INH and PZA are the most important elements in our current 'first-line' regimen. For most forms of uncomplicated childhood TB these three drugs are adequate. PZA completes most of its activity within the first 2 months of treatment; it is therefore customary to talk of an 'intensive' phase of treatment with INH, RMP and PZA, the main focus being to eliminate the bulk of the bacilli, and a …