BACKGROUND The increasing prevalence of stable derepressed mutants over-producers of type I chromosomal cephalosporinase in inducible Enterobacteriaceae and Pseudomonas aeruginosa challenges the adequacy of third generation cephalosporins in the empirical treatment of certain nosocomial infections. We sought to determine the frequency of stable over-producers of type I enzyme and their associated resistance to fluoroquinolones and aminoglycosides. METHODS Disc-diffusion and MIC determinations to extended-spectrum beta-lactams, imipenem, ciprofloxacin and gentamicin were performed in all cell isolates of inducible enteric bacteria (Enterobacter spp., Citrobacter spp., Serratia spp., Morganella morganii, Providencia spp.) and P. aeruginosa collected during the period of study (1992-1993). RESULTS A total of 1,426 isolates of inducible enteric bacteria and P. aeruginosa were studied. Each one represented a single patient. Among the 511 isolates of enteric bacteria 15.1% of strains were found to be stable derepressed mutants (Serratia 2.2%; Morganella spp., 3%; Providencia and Proteus 3%; Citrobacter spp., 10%; Enterobacter spp., 23.6%); among the 916 P. aeruginosa isolates studied, 9.2% were stable over-producers. Among Citrobacter, Providencia and Proteus spp., 53.1% of stable over-producers were resistant to ciprofloxacin versus 20.2% of non-over-producers (p < 0.01); in P. aeruginosa, 35.3% of over-producers were resistant to gentamicin versus 25.0% in non-over-producers (p < 0.01). CONCLUSIONS The prevalence of stable derepressed mutants is high among enteric bacteria and P. aeruginosa with type I inducible beta-lactamase. These strains frequently exhibit resistance to fluoroquinolones and aminoglycosides, reducing considerably the available therapeutic options.