The increasing prevalence of strains of common pathogenic bacteria resistant to widely available, relatively cheap antimicrobials included in the model list is, in many cases, dangerously eroding their effectiveness.

It is becoming increasingly common for important pathogens to emerge in a country or locality that are shown, on susceptibility testing, to have developed resistance to all normally appropriate essential drugs. In these circumstances a reserve antimicrobial is needed. A reserve antimicrobial is an antimicrobial that is useful for a wide range of infections but, because of the need to reduce the risk of development of resistance and because of its relatively high cost, it would be inappropriate to recommend its unrestricted use.

The concept of reserve antimicrobials is of practical relevance only when information is available on the prevailing susceptibilities of important bacterial pathogens. Many schemes have been initiated for laboratory-based monitoring of resistance to antimicrobials but there is a need for international coordination. It has already been emphasized that reference laboratories need to be established in developing as well as developed countries in order to monitor the resistance of important bacterial pathogens (32, 33). Knowledge of prevailing susceptibility patterns is vital to the selection and use of antimicrobials and to the development of appropriate prescribing policies. Without these data the health of seriously ill patients could be jeopardized. Knowledge of susceptibility patterns should come from proper laboratory investigations. Research directed towards improving the link between the results of laboratory testing and prescribing policies is needed. Decisions on drug use should be taken on the basis of standardized therapeutic efficacy testing.

The finding of high levels of resistance to rifampicin + isoniazid, known as multidrug-resistant tuberculosis, in some countries or localities emphasizes the need for the use of second-line anti-tuberculosis drugs in such locations. However, WHO strongly recommends that the prescription and use of such drugs be restricted to specialized centres with well trained staff and appropriate facilities as defined in the WHO guidelines for DOTS (directly observed treatment, short course)-Plus programmes for treatment of multidrug-resistant tuberculosis and be based on scientifically justified treatment regimens (34, 35). These drugs must not be made available outside the public sector, and should be under the strict control of govern-mental DOTS-Plus pilot projects. Such projects should be implemented only in areas with successful DOTS programmes for tuberculosis control.

The Committee considered the following drugs and formulations essential for the treatment of multidrug-resistant tuberculosis, as de-fined above:

• amikacin: powder for injection, 1000mg in vial
• p-aminosalicylic acid: tablet, 500 mg; granules, 4 g in sachet
• capreomycin: powder for injection, 1000mg in vial
• ciprofloxacin: tablet, 250 mg, 500 mg
• °cycloserine: capsule or tablet, 250 mg
• °ethionamide: tablet, 125 mg, 250 mg
• kanamycin: powder for injection, 1000mg in vial
• levofloxacin: tablet, 250 mg, 500 mg
• ofloxacin: tablet, 200 mg, 400 mg.

° Example of a therapeutic group.

In some countries, strains of Plasmodium falciparum have developed resistance to all of the antimalarial drugs except for artemisinin and its derivatives. For patients with falciparum malaria resistant to chloroquine, sulfadoxine + pyrimethamine, mefloquine, or quinine with tetracycline, the use of artemisinin and its derivatives appears essential. In order to limit the development of resistance to these drugs and keep them effective for as long as possible, their use should be restricted to areas in which multidrug-resistant falciparum malaria exists. In such countries artemisinin and its derivatives should be used for the treatment of uncomplicated infections resistant to all other antimalarials, or for severe falciparum malaria where quinine is ineffective. The Committee recognizes the importance of using artemisinin and its derivatives in combination with other antimalarial drugs to help address the problem of drug resistance (36).

The need for the discovery and development of new anti-infective drugs, especially for those diseases mainly prevalent in developing countries, continues to be of high priority.