title: Molecular epidemiology and multidrug resistance mechanisms of Pseudomonas aeruginosa isolates from Bulgarian hospitals.
abstract: A panel of 29 multidrug-resistant (MDR) Pseudomonas aeruginosa isolates recovered from seven hospitals as part of a country-wide surveillance of antimicrobial resistance in Bulgarian hospitals was studied. Molecular typing through multiple-locus variable number tandem-repeat analysis (MLVA6) yielded 23 different profiles. Phenotypic and genotypic tests for the detection of acquired carbapenemases yielded negative results in all cases. In contrast, 76% of the isolates produced other acquired β-lactamases, including extended-spectrum β-lactamases (ESBLs). Namely, 6 of the isolates (21%) produced a VEB-1 ESBL; 14 (48%) produced an OXA-10-type enzyme (7 OXA-10 and 7 OXA-10 ESBL variants, including 2 OXA-17 [A218G], 2 OXA-74 [C197T, A218G], and 3 OXA-142 [A218G, G470A]); 8 (28%) an OXA-2-type enzyme (all OXA-2); and 1 (3%) a PSE-1 carbenicillinase. Further analysis through multilocus sequence typing (MLST) revealed that the six VEB-1-producing strains, recovered from four hospitals, belonged to ST111 or ST244 international high-risk clones. Additionally, nearly all of the isolates (97%) lacked OprD production, explaining carbapenem resistance. Overexpression of AmpC was documented in 5 (17%) of the isolates, including most of the MDR isolates not producing any acquired β-lactamase. Particularly noteworthy was the very high prevalence of MexXY-OprM overexpression, documented in 72% of the isolates, whereas the prevalence of MexAB-OprM overexpression was lower (21%). In summary, while the production of metallo-β-lactamases is uncommon among P. aeruginosa isolates from Bulgarian hospitals, MDR profiles frequently result from the production of ESBLs combined with the lack of production of the carbapenem porin OprD and the overexpression of the MexXY-OprM efflux pump.
authors.affiliation: 1 Department of Microbiology, National Centre for Infectious and Parasitic Diseases , Sofia, Bulgaria .
authors.forename: Rossitza
authors.initials: R
authors.lastname: Vatcheva-Dobrevska
authors.forename: Xavier
authors.initials: X
authors.lastname: Mulet
authors.forename: Ivan
authors.initials: I
authors.lastname: Ivanov
authors.forename: Laura
authors.initials: L
authors.lastname: Zamorano
authors.forename: Elina
authors.initials: E
authors.lastname: Dobreva
authors.forename: Tzvetan
authors.initials: T
authors.lastname: Velinov
authors.forename: Todor
authors.initials: T
authors.lastname: Kantardjiev
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliver
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002031:Bulgaria / Q000453:epidemiology; D003428:Cross Infection / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D017720:Molecular Epidemiology; D058885:Multilocus Sequence Typing; D018272:Porins / Q000172:deficiency / Q000235:genetics; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D020080:Tandem Repeat Sequences; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D026901:Membrane Transport Proteins; C402791:MexXY protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D018272:Porins; C077157:OprD protein, Pseudomonas aeruginosa; D001618:beta-Lactamases