Pseudomonas aeruginosa GW-1 was isolated in 2000 in South Africa from blood cultures of a 38-year-old female who developed nosocomial pneumonia. This isolate harbored a self-transferable ca. 100-kb plasmid that conferred an expanded-spectrum cephalosporin resistance profile associated with an intermediate susceptibility to imipenem. A ␤-lactamase gene, bla GES-2 , was cloned from whole-cell DNA of P. aeruginosa GW-1 and expressed in Escherichia coli. GES-2, with a pI value of 5.8, hydrolyzed expanded-spectrum cephalosporins, and its substrate profile was extended to include imipenem compared to that of GES-1, identified previously in Klebsiella pneumoniae. GES-2 activity was less inhibited by clavulanic acid, tazobactam and imipenem than GES-1. The GES-2 amino acid sequence differs from that of GES-1 by a glycine-to-asparagine substitution in position 170 located in the omega loop of Ambler class A enzymes. This amino acid change may explain the extension of the substrate profile of the plasmid-encoded ␤-lactamase GES-2.Clavulanic acid-inhibited extended-spectrum ␤-lactamases (ESBLs) conferring resistance to expanded-spectrum cephalosporins have been reported, first in Enterobacteriaceae and then in Pseudomonas aeruginosa (11,23). Rare reports of TEM-and SHV-type ESBLs in P. aeruginosa are known (SHV2a, 23,31]), while they have been extensively described in Enterobacteriaceae (11). Three non-TEM-, non-SHV-type ESBLs have been reported in P. aeruginosa, i.e., PER-1, VEB-1, and OXA-18 ␤-lactamases (20,25,27,38). The PER-1 ␤-lactamase gene is widespread in Turkey, although not reported as plasmid mediated in P. aeruginosa (39). VEB-1 ␤-lactamase, originally described in Escherichia coli and Klebsiella pneumoniae isolates in Vietnam, has been found in P. aeruginosa and enterobacterial isolates in Thailand (8,29,38).We have recently identified another Ambler class A ␤-lactamase, GES-1, in a K. pneumoniae isolate in French Guiana (28). It was found to be remotely related to other ESBLs. This ESBL differs by two amino acid substitutions from IBC-1 ␤-lactamase recently found in an Enterobacter cloacae isolate in Greece (7). bla VEB-1 , bla GES-1 , and bla IBC-1 are plasmid located and are part of gene cassettes integrated into class 1 integrons (7,28,29).Mobile cassettes contain genes most often mediating antibiotic resistance and a cassette recombination site, designated the 59-base element (59-be) (9, 10). The 59-be sites vary in length (57 to 141 bp) and structure, but they are all bounded by a core site (GTTRRRY) at the recombinant crossover point and an inverse core site (RYYYAAC) at the 3Ј end of the inserted gene (4, 9). Integrons are genetic elements capable of integrating individual gene cassettes by a site-specific recombination mechanism that involves a DNA integrase, IntI; an integron-specific recombination site, attI; and 59-be (4, 9, 10). The 5Ј conserved segment (5Ј-CS) of the integrons contains the integrase gene (intI) and the recombination site attI1. The 3Ј-CS of class 1 integrons carries the antiseps...

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Eight Pseudomonas aeruginosa clinical strains that produce the clavulanic-acid-inhibited beta-lactamase GES-2 were isolated from patients of a South African hospital from March to July 2000. They were clonally related and each harboured a 150 kb conjugative plasmid carrying a class 1 integron containing a gene cassette encoding GES-2, followed by those for beta-lactamase OXA-5 and an aminoglycoside modifying AAC(3)I-like enzyme. Hence, incidences of infection, several fatal, due to bacteria displaying clavulanate-inhibited resistance to extended-spectrum cephalosporins and reduced susceptibility to imipenem in Pretoria Academic Hospital, South Africa, can be explained, at least in part, by the spread of P. aeruginosa expressing the GES-2 beta-lactamase.

These data confirm the potent in vitro activity of fidaxomicin against C. difficile. Moreover, this study provides an important baseline for ongoing long-term surveillance of antimicrobial resistance and prospective tracking of prominent and emerging strain types.

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