Nosocomial outbreak due to a multiresistant strain of Pseudomonas aeruginosa P12: Efficacy of cefepime-amikacin therapy and analysis of beta-lactam resistance

Over a 3-year period, 67 patients of the Hospital of Pau (Pau, Prance), inc luding 64 patients hospitalized in the adult intensive care unit (ICU), wer e colonized and/or infected by strains of Pseudomonas aeruginosa P12, resis tant to all potentially active antibiotics except colistin. Most patients w ere mechanically ventilated and presented respiratory tract infections. Sin ce cefepime and amikacin were the least inactive antibiotics by MIC determi nation, all ICU patients were treated with this combination, and most of th em benefited. Cefepime-amikacin was found highly synergistic in vitro. Ribo typing and arbitrary primer-PCR analysis confirmed the presence of a single clonal isolate. Isoelectrofocusing revealed that the epidemic strain produ ced large amounts of the chromosomal cephalosporinase and an additional enz yme with a pI of 5.7, corresponding to PSE-1, as demonstrated by PCR and se quencing. Outer membrane protein profiles on sodium dodecyl sulfate-polyacr ylamide gel electrophoresis showed the absence of a ca. 46-kDa protein, lik ely to be OprD, and increased production of two ca. 49- and 50-kDa proteins , consistent with the outer membrane components of the efflux systems, MexA B-OprM and MexEF-OprN. Thus, we report here a nosocomial outbreak due to mu ltiresistant P. aeruginosa P12 exhibiting at least four mechanisms of beta -lactam resistance, i.e., production of the penicillinase PSE-1, overproduc tion of the chromosomal cephalosporinase, loss of OprD, and overexpression of efflux systems, associated with a better activity of cefepime than cefta zidime.