Antimicrobial resistance - Judicious use is the key.

Antibiotics are used as agents to prevent and treat infections caused by pathogenic bacteria and other microbes. Their discovery ranks as one of the most important developments of modern medicine. Thousands of years ago, the Chinese were aware of the therapeutic potential of mouldy soybean curd applied to carbuncles and furuncles, and the ancient Greeks routinely used agents with anti-infective properties (such as myrrh and inorganic salts) in the treatment of infected wounds (1). The discovery of penicillin by Alexander Fleming in 1928, followed by the discovery and clinical use of sulphonamides in the 1930s, heralded the age of modern antimicrobial chemotherapy (1,2). Penicillin use became widespread in the 1940s. The use of sulphonamides and cephalosporins became widespread in the 1950s and 1960s, respectively. Two pioneers in the early antimicrobial chemotherapy era recognized that antimicrobial resistance was a significant concern. Fleming (2) reported that microbes were educated to resist penicillin, and that a host of penicillin-fast organisms were bred out which could be passed to other individuals, eventually leading to a pneumonia or septicemia for which penicillin would be ineffective. In 1942, Dubos noted that a vacuum was created when entire microbial populations were severely reduced, causing a profound impact on the natural equilibrium between host and microbes (3). The phenomenon of antimicrobial resistance is an aspect of microbial ecology that developed almost immediately after the first antibiotics were used. This phenomenon represents a means of survival presented to a threatened microbial population, and occurs through genetic mutation, expression of a latent resistance gene or the acquisition of genes with resistance determinants (4,5). These three occurrences are not mutually exclusive and may coexist within a given bacterium. The widespread use of antibiotics provides selective pressure favouring the propagation of resistant organisms. These selective pressures create opportunities for resistant strains to emerge, multiply and be transmitted. Levy (6) reminded us of possible ecological imbalances that may be established, and suggested that the reversibility of the selection process is dependent on repopulation by the original susceptible bacteria. Antibiotic resistance is acknowledged as one of the most serious threats to the treatment of infectious diseases on a global basis. This threat prompted the World Health Organization to issue a warning that antibiotic resistance threatens to rob the world of opportunities to treat or cure many infectious diseases (7). Antibiotic-resistant organisms erode our therapeutic inventory and cause significant increases in the cost and toxicity of newer drugs (8). Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), multiply antibioticresistant Shigella and Salmonella species, resistant enteric gramnegative bacilli (Escherichia and Klebsiella-Enterobacter species) and penicillin-resistant Streptococcus pneumoniae (PRSP) are examples of microorganisms with increasing rates of resistance to commonly used antimicrobials. Traditionally, PRSP and multiply resistant Shigella and Salmonella species are more common in the community setting, while MRSA, VRE and resistant enteric Gram-negative bacilli are more common in health care facilities. The isolation of penicillin-resistant S aureus was reported shortly after penicillin became widely available. Initially a sporadic occurrence, this type of resistance (borne by a plasmid) spread rapidly through the 1950s and 1960s. By the 1970s, almost all hospital strains and a large number of community strains of S aureus were penicillin-resistant, and Canada was no exception. The development of semisynthetic penicillinaseresistant agents, methicillin and isoxazolyl penicillins in 1960 was followed by the report of MRSA in the early 1960s (9). MRSA has since been reported from both acute care and longterm care facilities in Canada throughout the past two decades (10,11). Recent data from the Canadian Nosocomial Infection Surveillance Program (CNISP) revealed that the proportion of S aureus isolates (representing both colonization and infection) reported as being methicillin-resistant increased from 1.0/100 isolates (0.5/1000 admissions) in 1995 (12) to 10/100 isolates (5.4/1000 admissions) in 2003 (Health Canada, unpublished data). The majority of MRSA reports (69%) (including both colonization and infection) were from central Canada, with the remainder from western (20%) and eastern (11%) Canada. This pattern of increase in the past eight years is disconcerting, with the majority of the isolates coming from acute care health care facilities. VRE was first reported in Canada in 1993 (13) and it has been recognized in all of the provinces, predominantly as colonization being found in surveillance cultures. The VRE Passive Reporting Network, established within the CNISP, identified 1315 instances of VRE throughout Canada between 1994 and 1998, with less than 5% representing infection (14). Since 1999 (the year a prospective surveillance system was established within the CNISP), the rate of VRE isolates has increased from 0.15/100 to 0.26/100 enterococcal isolates (15). This rate is still relatively low, especially when compared with rates from the United States, where prevalence of nosocomial VRE increased from 0.3% in 1989 to 23% in 1999 (16,17). Despite the geographical proximity of Canada and the United States,