Dynamics of a nosocomial outbreak of multidrug-resistant Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta-lactamase

From November 1998 to August 1999, a large outbreak occurred in the general intensive care unit of the Ospedale di Circolo in Varese (Italy), caused b y Pseudomonas aeruginosa producing the PER-1 extended-spectrum beta -lactam ase. A total of 108 clinical isolates of P. aeruginosa resistant to broad-s pectrum cephalosporins were recovered from 18 patients. Epidemic isolates w ere characterized by synergy between clavulanic acid and ceftazidime, cefep ime, and aztreonam. Isoelectric focusing of crude bacterial extracts detect ed two nitrocefin-positive bands with pI values of 8.0 and 5.3. PCR amplifi cation and characterization of the amplicons by restriction analysis and di rect sequencing indicated that the epidemic isolates carried a bla(PER-1) d eterminant. The outbreak was of clonal origin as shown by pulsed-field gel electrophoresis analysis. This technique also indicated that the epidemic s train was not related to three other PER-1-positive isolates obtained at th e same hospital in 1997. Typing by enterobacterial repetitive intergenic co nsensus-PCR showed that minor genetic variations occurred during the outbre ak The epidemic strain was characterized by a multiple-drug-resistance phen otype that remained unchanged over the outbreak, including extended-spectru m cephalosporins, monobactams, aminoglycosides, and fluoroquinolones. Isola tion of infected patients and appropriate carbapenem therapy were successfu l in ending the outbreak Our report indicates that the bla(PER-1) resistanc e determinant may become an emerging therapeutic problem in Europe.