Dr M. Inoue, Japan

Transportation of meat and agricultural products has increased as a consequence of continuous population growth, urbanization, extensive movement of people, and liberalization of the market. As a result, outbreaks of new and existing infectious diseases on a global scale have been generated, including the spread of infection by resistant bacteria.

Development and clinical application of new antimicrobial drugs has been followed by the emergence of resistant bacteria several years later. Thus, a cycle of use of antimicrobial drugs and emergence of resistant bacteria has been repeated. Japan is not an exception to this trend.

Multiple drug-resistant Shigella emerged in the 1950s, multiple drug resistant Staphylococcus aureus appeared in the ig6os, and ampicillin-resistant enterobacterium and Pseudomonas aeruginosa emerged in the 1970s. Recently, attention has been drawn to the emergence of multiresistent S. aureus (MRSA), penicillin-resistant Streptococcus pneumoniae (PRSP), beta -lactamase-negative penicillin-resistant Haemophilus influenzae (called BLANAR) and GISA, as well as to that of carbapenem-resistant Pseudomonas aeruginosa and Serratia.

Resistant bacteria which have emerged as a result of carbapenem hydrolysis of bacteria, Pseudomonas aeruginosa, in particular, have raised a problem unique to Japan. However, such resistant bacteria have been confined to some specific hospitals, and have not been a uniform phenomenon of all bacteria isolated in Japan.

Emergence of drug-resistant bacteria is often closely associated with the status of the use of antimicrobial drugs. However, when biochemical analysis of the mechanism of drug resistance, analysis of drug-resistant genes and identification of resistant bacteria by DNA diagnosis are taken into consideration globally, the inevitable conclusion is that other factors are also involved.

An antimicrobial agent which is suspected of losing its effectiveness because of emergence of resistant bacteria would normally be eliminated during the development stage. Therefore, there must have been no reason for concern about the emergence of resistance at that time. If resistant isolates to these drugs emerged, it must be assumed that the users or some other factors, but not the drugs themselves, were responsible.

When the types of enzyme-producing genes isolated in Japan were compared with those isolated in Europe and the United States, where they have caused a problem, identical types were not detected. Instead, two types of enzymes which are unique to Japan, were found. These results indicate that the emergence of resistant bacteria depends upon differences in the kinds of antimicrobial drugs in each country.

Why do antimicrobial agents become ineffectual? How can resistant bacteria appear in clinical settings? The evidence suggests that several genes will undergo mutation until strong resistance against cefalosporin, which is currently used in clinical settings, is established. It also suggests that it is not easy for bacteria to acquire strong resistance.

The development of antimicrobial drugs has been slowing down. It has been suggested that we cannot expect in the near future the brilliant achievements we saw in the ig8os. It is therefore crucial that, by wisely using these drugs, we prevent the emergence of resistant bacteria and maintain the efficacy of antimicrobial drugs which are currently employed in the treatment of infectious diseases in clinical settings.

Accordingly, the Japanese Ministry of Health and Welfare has recommended that the Government develop a comprehensive law aimed at preventing infectious diseases. This legislation would focus on the treatment of disease, and would stipulate ways to prevent infection and to deal with diseases when they break out. The law would cover seventy types of infectious diseases, including VRE, MRSA, and PRSP infections, and categorize them into four types based on their infectious ability and symptoms. The proposed law represents a change from current legislation, which simply requires quarantine to prevent epidemics. In conclusion, applied research should be conducted in order to use our scientific knowledge and skills for the benefit of society.