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 Proteus mirabilis increased to 8.8% of all P. mirabilis isolates during the period 1997-1999. To evaluate the susceptibility of ESBL-producing P. mirabilis strains against commonly used drugs, we studied 50 non-duplicated isolates selected on the basis of synergy between clavulanate and beta-lactams (ceftazidime, aztreonam, cefotaxime, and ceftriaxone). The presence of ESBL-coding genes was confirmed by colony hybridization with bla(TEM-1) and bla(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-52) were present. These enzymes have not been previously reported in P. mirabilis. Isolates were characterized by: (a) reduced susceptibility or resistance to third- and fourth-generation cephalosporins (MIC > or = 2 mg/l), (b) resistance to piperacillin that was abolished by tazobactam (MIC > or = 256 vs. < or = 2 mg/l, respectively), (c) multiple antibiotic resistance that included gentamicin, fluoroquinolones and co-trimoxazole. Therapeutic failure and lack of eradication of ESBL-positive P. mirabilis by third-generation cephalosporins has been repeatedly observed both at our Institution and elsewhere. Piperacillin-tazobactam, as well as amikacin and meropenem appear to be important therapeutic options for infections due to multidrug-resistant, ESBL-producing P. mirabilis isolates.
Luzzaro
F
F
Laboratory of Medical Microbiology, Ospedale di Circolo e Fondazione Macchi and University of Insubria, Varese, Italy. fluzzaro@ospedale.varese.it
Perilli
M
M
Amicosante
G
G
Lombardi
G
G
Belloni
R
R
Zollo
A
A
Bianchi
C
C
Toniolo
A
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002511:Cephalosporins / Q000494:pharmacology; D019818:Clavulanic Acid / Q000494:pharmacology; D004352:Drug Resistance, Microbial; D018432:Drug Resistance, Multiple; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005798:Genes, Bacterial; D006801:Humans; D008826:Microbial Sensitivity Tests; D010397:Penicillanic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D011512:Proteus Infections / Q000188:drug therapy / Q000382:microbiology; D011513:Proteus mirabilis / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000078142:Tazobactam; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
D000900:Anti-Bacterial Agents; D002511:Cephalosporins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D019818:Clavulanic Acid; D010397:Penicillanic Acid; D001618:beta-Lactamases; C034413:beta-lactamase TEM-1; D000078142:Tazobactam