Widespread Multi-Antimicrobial- Resistant Shigella in Asia: What Does It Mean? Chiang Mai, Thailand March 30 – April 2, 2004 Second International Conference on Improving Use of Medicines Okumura J 1), Osaka K 2), Okabe N 2) 1)University of Tokyo 2)National Institute of Infectious Diseases, Japan

Background Despite immense efforts to contain antimicrobial resistance (AMR), development of resistant microbes has been accelerated. For example, Shigella sonnei, spread by travelers, illustrates the problems caused by resistant microbes and the urgency of its containment. Second International Conference on Improving Use of Medicines

Objectives To understand the trend of development and distribution of resistant S. sonnei in Asia. To identify factors by which the world has been failing to contain AMR, in spite of holding a number of expert meetings and a mountain of documents on the agenda. To seek effective and practical measures to halt the spread of AMR before it reaches at critical level. Second International Conference on Improving Use of Medicines

Methods (1) Design: Retrospective, time series Samples: Imported S. sonnei which were isolated from travelers at quarantine stations in Japan 120, 87 and 159 samples each year during the period of 1997 – 1999 Second International Conference on Improving Use of Medicines

Methods (2) Checked AMR of the isolated S. sonnei by measuring Minimum Inhibitory Concentration (MIC): By using E-test ® (AB Biodisk) on agar media Antimicrobials are: Ampicillin (ABPC), Chloramphenicol (CP), Cefotaxime (CTX), Fosfomycin (FOM), Levofloxacin (LVFX), Norfloxacin (NFLX), Tetracycline (TC), Sulfamethoxazole-Trimethoprim (ST) Referred the National Committee for Clinical Laboratory Standards Second International Conference on Improving Use of Medicines E-test ®

Overall trend of AMR Second International Conference on Improving Use of Medicines n = 120n = 159n = 87

Trend and level of AMR in 3 countries Second International Conference on Improving Use of Medicines n=43n=26n=72n=7n=18n=38n=14n=17

Resistance by Antimicrobials in Indonesia Second International Conference on Improving Use of Medicines %

Resistance by Antimicrobials & Expenditure for Antimicrobials for Human in Thailand Second International Conference on Improving Use of Medicines Million Bhats FOM Resistant Strain %

Resistance to 2 nd or 3 rd line antimicrobials: All the S. sonnei developed resistance to NFLX also attained resistance to more than three antimicrobials (P<0.001). Second International Conference on Improving Use of Medicines FOM Total ResistantSensitive Resistance to: 4 or more or less Odds Ratio: 10.4 (95% CI: 4.0 – 27.2) P<0.001 Multiple Resistance and Susceptibility to FOM (Unit: Strain)

Lessons learned In spite of immense efforts to contain AMR during the last century, the problem has been unsolved and AMR strains become easily transmitted in the current highly mobile world. e.g.1, The World Health Assembly (WHA) Resolution of 1988 urged member states to take actions to contain AMR. e.g.2, The current efficacy of Antimicrobial Resistance Information Bank (A-R Info Bank) is questionable. The velocity of AMR development has been accelerated hence no effective antimicrobials may exist in the near future. There might be accumulated data on AMR in each country, which are however least likely used for the purpose of AMR containment. Second International Conference on Improving Use of Medicines

Implications Establishment of monitoring and information sharing systems is urgently needed, which cover sensitivity of antimicrobials, its consumption and usage. The system should be reciprocal one, which can be accessed by Internet. If Internet access is difficult, at least quarterly reports should be distributed. Strong political commitment and a sense of urgency of each stakeholder, are needed to establish and maintain the reciprocal system, such as smallpox eradication programme. Second International Conference on Improving Use of Medicines

Research Agenda For the monitoring system, key microbes should be determined with considering test cost, required skill, severity of problems. Also, targeted antimicrobials should be determined. The efficacy of the reciprocal monitoring system should be carefully monitored and evaluated: Baseline data analysis Regular submission and utilization of relevant data Changes in antimicrobial consumption and AMR development among key microbes Second International Conference on Improving Use of Medicines

Conclusions Before establishing the system, a certain period is needed for the preparation. However, by utilizing the existing platform (e.g., national data on AMR and Antimicrobial consumption in several countries), it can be initiated shortly in some regions. Each country should be responsible for their antimicrobial use and understand we live in highly mobile world. Second International Conference on Improving Use of Medicines