RESEARCH bloodstream; respiratory tract, including lower respiratory tract and pneumonia; urinary tract; and surgical site infections) (21,22). Isolates were considered nosocomial if the culture was dated >2 days after admission. All isolates were identified by standard methods and confirmed by using Vitek or API prod- ucts (bioMerieux Vitek, Inc., Hazelwood, MO). For determin- ing the percentage of resistance, the same organisms from multiple blood cultures or from the same sources with identical antibiotype were considered a single isolate. The amount of use for each indicated antimicrobial agent (including oral and parenteral forms) was expressed in grams per 1,000 inpatient- days. Antimicrobial Susceptibility Testing Antimicrobial susceptibility testing of the bacterial isolates was performed by the disk diffusion method as described by the National Committee for Clinical Laboratory Standards (NCCLS) (23). S. aureus ATCC 25923, E. coli ATCC 25922, and P. aeruginosa ATCC 27853 were included as control strains. Interpretive criteria for susceptibility or resistance fol- lowed NCCLS guidelines (23). For this report, we present sus- ceptibility data for penicillin, oxacillin, vancomycin, gentamicin, cefotaxime, ceftazidime, imipenem, and ciproflox- acin. The susceptibility data for imipenem and ciprofloxacin were available only since 1993; those for other agents were available from 1981 to 1999. Antifungal susceptibility testing of amphotericin B and flu- conazole against 150 blood isolates of Candida species col- lected from October 1997 to September 1999 was performed by the E test (AB BIODISK, Solna, Sweden) according to the manufacturer’s instructions. Quality control was performed by testing C. parapsilosis ATCC 2019 and C. krusei ATCC 6258. MIC results were interpreted in accordance with NCCLS guidelines (24). Results During the 19-year period, 35,580 bacterial pathogens causing nosocomial infections were identified. The hospital’s overall rate of nosocomial infections during the 19-year period ranged from 3.9% to 6.1%. For the four major sites of nosoco- mial infections, data are presented as numbers of infection per 10,000 patient-days from 1991 to 1999 (Figure 1). BSI ranked first in nosocomial infection sites in 1999, followed by urinary tract, surgical site, and respiratory tract infections. Data for the catheter- and ventilator-days of the hospital- ized patients were not available. However, the mean percent- ages of patients who stayed in ICUs (six medical ICUs and six surgical ICUs) and used urinary catheters, arterial and central venous catheters, and ventilators were 75.0%, 77.9%, 63.2%, respectively, in 1996 and 79.4%, 81.4%, and 65.2%, respec- tively, in 1999. The incidence (number of infections/patient- days x 1,000) of urinary catheter-related urinary tract infection, vascular catheter-associated BSI, and ventilator-associated pneumonia in the ICUs was 4.4, 5.6, and 2.7, respectively, in 1996 and 6.0, 7.1, and 3.4, respectively, in 1999. Figure 1. Rates of four major nosocomial infections expressed as num- ber of infections per 10,000 patient-days at National Taiwan University Hospital from 1991 to 1999. BSI, bloodstream infection; UTI, urinary tract infection; SSI, surgical site infection; RTI, respiratory tract infec- tion. Gram-negative bacteria remained the predominant patho- gens (66.1% in 1981, 51.3% in 1993, and 53.4% in 1999); however, incidences of fungal infections have increased recently (Table 1). In a comparison of data grouped into four time periods (1981-1986, 1987-1992, 1993-1998, and 1999), E. coli decreased from 12.1% of all nosocomial infections in 1981-1986 to 9.5% in 1993-1998; however, infections caused by S. aureus increased from 5.2% (1981-1986) to 12.1% (1993-1998). Candida species showed a considerable increase (from 3.7% in 1981-1986 to 16.2% in 1999) and have ranked first since 1993, followed by S. aureus and P. aeruginosa (Table 1). Candida species, S. aureus, and Acinetobacter species were also important bloodstream isolates (Table 1), increasing from 1.0%, 5.2%, and 6.1%, respectively, in 1981-1986 to 16.2%, 13.0%, and 7.6%, respectively, in 1999. Although E. coli was also a frequent isolate, it declined in percentage of all BSI from 18.7% in 1981-1986 to 9.0% in 1999. Other patho- gens declining in percentage of BSI from 1981-1986 to 1999 included K. pneumoniae, P. aeruginosa, and Enterococcus spe- cies. From 1992 to 1999, 1,065 isolates of Candida species were recovered from patients with nosocomial BSIs. C. glabrata (8.8%) ranked fourth in incidence behind C. albicans (59.3%), C. tropicalis (17.6%), and C. parapsilosis (8.2%) in 1999. Only four blood isolates of C. krusei were identified during the 8-year period. The most frequent isolates from urinary tract infections in 1993-1998 were Candida species (23.6%), followed by E. coli (18.6%) and P. aeruginosa (11.0%). However, in 1999, E. coli (18.4%) replaced Candida species (14.3%) as the top-ranking pathogen causing urinary tract infections. P. aeruginosa remained the most frequent isolate for respiratory tract and sur- gical site infections in the past 13 years. Candida species increased in incidence in surgical site infections, from 1.8% in 1981-1986 to 6.4% in 1999. Among pathogens causing respira- tory tract infections, Acinetobacter species ranked fifth in 64 Emerging Infectious Diseases • Vol. 8, No. 1, January 2002