Pseudomonas aeruginosa is an opportunistic pathogen that causes a variety of nosocomial infections. Cefepime (FEP) and ceftazidime (CAZ) are broad-spectrum cephalosporins that display similar MICs for wild-type P. aeruginosa strains. Although the rates of susceptibility of these two antipseudomonal cephalosporins appear to be identical for P. aeruginosa isolates in the United States (20), several European studies have recently reported an unusual discordance in the MICs of FEP and CAZ (4, 6, 7), with P. aeruginosa isolates being less susceptible to the former cephalosporin.The most frequent mechanisms of resistance to extendedspectrum cephalosporins in P. aeruginosa are derepression of the chromosomal AmpC ß-lactamase, the impermeability of the outer membrane, and increased efflux (9). FEP, in contrast to CAZ, is efficiently extruded by various efflux pumps, including the MexCD-OprJ and MexXY-OprM efflux pumps (16,22). In addition, previous studies have noted the selectively reduced susceptibility to FEP among P. aeruginosa strains producing OXA ß-lactamases (2), as opposed to those that produce class A extended-spectrum ß-lactamases (32), which usually confer resistance to CAZ and FEP.In response to an increase in the incidence of carbapenemresistant and multidrug-resistant P. aeruginosa isolates in the Hospital de Bellvitge, Barcelona, Spain, since 2004, a microbiology surveillance program was introduced. Recently, however, P. aeruginosa isolates showing variable susceptibilities to carbapenems and a discordance in susceptibility between CAZ and FEP have been noted. A clustering of the P. aeruginosa non-FEP-susceptible and CAZ-susceptible (Fep ns Caz s ) phenotype was suspected in the hospital's intensive care unit (ICUs). Here we elucidate the clinical and molecular epidemiology of the isolates with this discordant phenotype and the resistance mechanisms involved.
MATERIALS AND METHODSHospital setting. The Hospital de Bellvitge is a university-affiliated public institution for adult patients located in Barcelona, Spain. It contains 900 beds for acute medical and surgical care but no wards for pediatrics, obstetrics, or burns. The hospital has two 12-bed medical-surgical ICUs managed by separate teams of medical and nursing staff. The paramedical care providers (physiotherapists, radiographic personnel, nutrition support team) have contact with patients in both ICU units. All rooms in the ICUs are single.Data collection-outbreak detection.