For the period from 1999 to 2002 in the United States, the in vitro susceptibilities of 52,637 Pseudomonas aeruginosa isolates to 10 antimicrobial agents were evaluated. The isolates were from 29 laboratories, 11 of which participated in The Surveillance Network for four consecutive years. Isolates were collected from adult patients (>18 years of age) in intensive care units (ICU), non-ICU inpatients, nursing home patients, and outpatients; data were analyzed to evaluate factors, such as year of isolation, patient age group, isolate specimen source, and patient type (hospitalized patients [ICU, non-ICU, or nursing home] or outpatients). Rates of resistance for the 4-year period were highest for isolates from patients in ICU and 18-to 39-year-old patients and for isolates from the lower respiratory tract. Resistance decreased with age. Resistance was lowest in isolates from outpatients, in isolates from >70-year-old patients, and from specimens from the upper respiratory tract. Multidrug resistance (MDR) (resistance to three or more antimicrobial agents) accounted for 24.9% of all isolates. The MDR rate was highest in isolates from patients in nursing homes (29.9%) and ICU (29.5%).Infection with Pseudomonas aeruginosa is a serious problem affecting hospitalized patients, particularly those who are critically ill and immunocompromised, such as patients with cystic fibrosis, neutropenia, iatrogenic immunosuppression, or disrupted anatomical barriers (3,8). P. aeruginosa only occasionally causes serious infections in otherwise healthy persons and is infrequently identified as normal microbial flora in healthy individuals (8). Rates of colonization with P. aeruginosa increase in hospitalized patients, particularly in those who have been hospitalized for extended periods of time and/or have received broad-spectrum antimicrobial therapy or cancer chemotherapy. These increasing resistance rates have greatly limited the number of therapeutic choices (9, 10, 11).P. aeruginosa is a common human saprophyte that is able to adapt to a multitude of physical and nutritional environments and survive in large numbers in close proximity to its host. For these reasons, it is found in a broad range of infections. Infections caused by P. aeruginosa range from superficial skin infections to more serious infections, such as meningitis, endocarditis, and osteomyelitis, to fulminant sepsis (15). Antimicrobial resistance among clinical isolates of P. aeruginosa may complicate the treatment of infections and can adversely affect clinical outcomes and patient treatment costs (1, 5). New antimicrobial agents with activity against P. aeruginosa will not be available in the near future, making ongoing surveillance of the activities of currently available agents of critical importance.Although several surveillance studies have reported on the relative in vitro activities of various antimicrobial agents (4, 6, 7, 13, 16), an extensive comparative statistical analysis of resistance to antimicrobial agents relative to factors associated with resis...