RESEARCH Antimicrobial Drug Resistance in Pathogens Causing Nosocomial Infections at a University Hospital in Taiwan, 1981–1999 Po-Ren Hsueh, Mei-Ling Chen, Chun-Chuan Sun, Wen-Hwei Chen, Hui-Ju Pan, Li-Seh Yang, Shan-Chwen Chang, Shen-Wu Ho, Chin-Yu Lee, Wei-Chuan Hsieh, and Kwen-Tay Luh To determine the distribution and antimicrobial drug resistance in bacterial pathogens causing nosocomial infections, surveillance data on nosocomial infections documented from 1981 to 1999 at National Taiwan Uni- versity Hospital were analyzed. During this period, 35,580 bacterial pathogens causing nosocomial infections were identified. Candida species increased considerably, ranking first by 1999 in the incidence of pathogens causing all nosocomial infections, followed by Staphylococcus aureus and Pseudomonas aeruginosa. Can- dida species also increased in importance as bloodstream infection isolates, from 1.0% in 1981-1986 to 16.2% in 1999. The most frequent isolates from urinary tract infections were Candida species (23.6%), fol- lowed by Escherichia coli (18.6%) and P. aeruginosa (11.0%). P. aeruginosa remained the most frequent iso- lates for respiratory tract and surgical site infections in the past 13 years. A remarkable increase in incidence was found in methicillin-resistant S. aureus (from 4.3% in 1981-1986 to 58.9% in 1993-1998), cefotaxime- resistant E. coli (from 0% in 1981-1986 to 6.1% in 1993-1998), and cefotaxime-resistant Klebsiella pneumo- niae (from 4.0% in 1981-1986 to 25.8% in 1993-1998). Etiologic shifts in nosocomial infections and an upsurge of antimicrobial resistance among these pathogens, particularly those isolated from intensive care units, are impressive and alarming. The emergence of resistance to antimicrobial agents is a glo- bal public health problem, particularly in pathogens caus- ing nosocomial infections (1-5). Antimicrobial resistance results in increased illness, deaths, and health-care costs (1,2,6- 10). The distribution of pathogens causing nosocomial infec- tions, especially antimicrobial-resistant pathogens, changes with time and varies among hospitals and among different locations in the same hospital (11-15). The increasing number of immunocompromised patients and increased use of indwell- ing devices, as well as widespread use of antimicrobial agents in hospital settings, particularly in intensive care units (ICUs), contributes to antimicrobial resistance among pathogens caus- ing nosocomial infections (1,4,6,10). Surveillance data reported by the National Nosocomial Infections Surveillance (NNIS) System for 1993-1997 com- pared with January-November 1998 show a continuing increase in antimicrobial-resistant pathogens associated with nosocomial infections in ICU patients from U.S. hospitals (2). The increase is particularly marked for vancomycin-resistant enterococci (VRE) (55%), methicillin-resistant Staphylococcus aureus (MRSA) (31%), third-generation cephalosporin-resis- tant Escherichia coli (29%), imipenem-resistant Pseudomonas National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan aeruginosa (32%), and quinolone-resistant P. aeruginosa (89%) (2). Studies since 1990 have clearly demonstrated that Candida species continue to be an important cause of nosoco- mial infections, particularly of bloodstream infections (BSI). Furthermore, the proportion of BSI caused by Candida species other than C. albicans is increasing (14,16-20). We describe the distribution of major bacterial pathogens causing nosocomial infections from 1981 to 1999 in National Taiwan University Hospital and demonstrate the emergence of antimicrobial drug resistance among these pathogens during this period. Materials and Methods Data Collection National Taiwan University Hospital is a 2,000-bed tertiary referral center in Taipei, northern Taiwan. Available data for inpatient-days at the hospital ranged from 294,946 in 1990 to 566,165 in 1999. The number of ICU beds increased from 40- 50 before 1993 to 100-120 in 1998-99. The Nosocomial Infec- tion Control Committee of the hospital was established in 1980 to identify pathogens causing nosocomial infections and to obtain and analyze antimicrobial susceptibility results of these pathogens from the hospital’s clinical microbiology laboratory. NNIS definitions were used for nosocomial infections (e.g., Emerging Infectious Diseases • Vol. 8, No. 1, January 2002 63