Properties of multidrug-resistant, ESBL-producing Proteus mirabilis isolates and possible role of beta-lactam/beta-lactamase inhibitor combinations

At our institution, isolation rates of clinical strains of ESBL-producing P roteus mirabilis increased to 8.8% of all P. mirabilis isolates during the period 1997-1999. To evaluate the susceptibility of ESBL-producing P. mirab ilis strains against commonly used drugs, we studied 50 non-duplicated isol ates selected on the basis of synergy between clavulanate and beta -lactams (ceftazidime, aztreonam, cefotaxime, and ceftriaxone). The presence of ESB L-coding genes was confirmed by colony hybridization with bla(TEM-1) and bl a(SHV-1) probes. Minimum inhibitory concentrations of several antimicrobial agents for each isolate were obtained using the Etest method. All strains were encoding for TEM-derived enzymes. Gene sequencing showed that at least three different genes (TEM-15, TEM-20, and TEM-57) were present. These enz ymes have not been previously reported in P. mirabilis. Isolates were chara cterized by: (a) reduced susceptibility or resistance to third- and fourth- generation cephalosporins (MIC greater than or equal to 2 mg/l), (b) resist ance to piperacillin that was abolished by tazobactam (MIC greater than or equal to 256 vs. less than or equal to2 mg/l, respectively), (c) multiple a ntibiotic resistance that included gentamicin, fluoroquinolones and co-trim oxazole. Therapeutic failure and lack of eradication of ESBL-positive P. mi rabilis by third-generation cephalosporins has been repeatedly observed bot h at our Institution and elsewhere. Piperacillin-tazobactam, as well as ami kacin and meropenem appear to be important therapeutic options for infectio ns due to multidrug-resistant, ESBL-producing P. mirabilis isolates. (C) 20 01 Elsevier Science B.V. and International Society of Chemotherapy. All rig hts reserved.