ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, June 2004, p. 2344–2345
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0066-4804/04/$08.00⫹0 DOI: 10.1128/AAC.48.6.2344–2345.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.
Emergence of the Extended-Spectrum ␤-Lactamase GES-1 in a Pseudomonas
aeruginosa Strain from Brazil: Report from the SENTRY Antimicrobial
Surveillance Program
The extended-spectrum ␤-lactamase (ESBL) GES-1 was ini-
tially described from a Klebsiella pneumoniae strain in 1998 (5).
Since then, two closely related enzymes, IBC-1 and GES-2,
have also been described (4, 6). A GES-1-producing K. pneu-
moniae strain has been reported from a French hospital, al-
though the patient had just been transferred from French
Guiana, South America. blaGES-1 has also been found in a
Pseudomonas aeruginosa strain isolated in another French
medical center (3) and in K. pneumoniae in Lisbon, Portugal
(2).
The GES-1-producing P. aeruginosa, isolate 48-8896, was
recovered from a 63-year-old female who had a hysterectomy
(São Paulo, Brazil) and developed a wound infection while
receiving ceftriaxone, amikacin, and metronidazole. Blood cul-
tures were drawn and were positive for P. aeruginosa. Poly-
myxin B plus vancomycin was started empirically and the in-
fection was eradicated, but the patient died after being
hospitalized in the intensive care unit for 3 months. Isolate
48-8896 showed resistance to imipenem MIC, ⬎8 ␮g/ml),
meropenem (MIC, ⬎8 ␮g/ml), ceftazidime (MIC, ⬎16 ␮g/ml),
cefepime (MIC, ⬎16 ␮g/ml), piperacillin-tazobactam (MIC,
⬎64 ␮g/ml), and all antimicrobial agents evaluated (including
aminoglycosides and quinolones), except for polymyxin B
(MIC, ⱕ1 ␮g/ml). Phenotypic detection of ESBL was deter-
mined to be positive using the (ceftazidime/ceftazidime-clavu-
FIG. 1. Schematic representations of different blaGES-1-containing integrons (a, b, c). The location of the three G residues found in the P2 of
P. aeruginosa 48-8896 is highlighted. The 59 bp are represented with black dots.
2344
Vol. 48, No.
lanic acid and cefepime/cefepime-clavulanic acid) Etest strips
(AB BIODISK, Solna, Sweden).
Since several ␤-lactamase genes are part of gene cassettes
Downloaded from http://aac.asm.org/ on March 23, 2015 by GEORGIAN COURT UNIV
that are class 1 integron mediated and most of them contain an
aminoglycoside acetyltransferase gene cassette, primers lo-
cated in the 5⬘ conserved segment region (5⬘-CS) (5⬘-CCAAG
CTCTCGGGTAACATC-3⬘) and in the flanking region of the
aacA4 gene cassette (5⬘-AACTTGCGAGCGATCCGATG-3⬘)
were used. PCR amplification and subsequent sequencing
analyses of the 1,211-bp PCR product showed a blaGES-1 in the
first position of a class 1 integron (Fig. 1).
The integron harboring blaGES-1 showed a similar adjacent
and upstream context as described in the first report of GES-1
(K. pneumoniae ORI-1) (5). Beyond blaGES-1 was intI1, encod-
ing the integrase of a class 1 integron. Between blaGES-1 and
intI1 was an attI1 site and two promoters (P2 and Pant). How-
ever, the P2 promoter appears to have an absence of three G
residues, and the space between the ⫺35 and ⫺10 sequences is
14 bp (Fig. 1). The secondary promoter (P2) is created by the
insertion of the three Gs, increasing the space between the
⫺35 and ⫺10 regions to 17 bp (1). This evidence suggests that
P2 was probably not contributing to the transcription of
blaGES-1, as previously described in other integrons harboring
this ESBL gene (3, 5). As determined in this study, beyond the
blaGES-1 integron lies a chloramphenicol-acetyltransferase
VOL. 48, 2004 LETTERS TO THE EDITOR 2345

gene cassette, catB8, followed by the 3⬘-CS region of the class
1 integron, which is unique among blaGES-1 genes.
The detection of a GES-1-producing P. aeruginosa isolate in
Latin America (Brazil) was a very worrisome finding, since it
heralds the possibility for the emergence and future dissemina-
tion of new GES derivatives with broader spectrums of hydroly-
ses, such as the carbapenem-hydrolyzing enzyme GES-2 (6).
The SENTRY program was funded by an educational research grant
from Bristol-Myers Squibb.
2. Duarte, A., F. Boavida, F. Grosso, M. Correia, L. M. Lito, and J. M. Cristino.
2003. Outbreak of GES-1-lactamase-producing multidrug-resistant Klebsiella
pneumoniae in a university hospital in Lisbon, Portugal. Antimicrob. Agents
Chemother. 47:1481–1482.
3. Dubois, V., L. Poirel, C. Marie, C. Arpin, P. Nordmann, and C. Quentin. 2002.
Molecular characterization of a novel class 1 integron containing blaGES-1 and
a fused product of aac3-Ib/aac6⬘-Ib⬘ gene cassettes in Pseudomonas aerugi-
nosa. Antimicrob. Agents Chemother. 46:638–645.
4. Giakkoupi, P., L. Tzouveleskis, A. Tsakris, V. Loukova, D. Sofianou, and E.
Tzelepi. 2004. IBC-1, a novel integron-associated class A ␤-lactamase with
extended-spectrum properties produced by an Enterobacter cloacae clinical
strain. Antimicrob. Agents Chemother. 44:2247–2253.
5. Poirel, L., I. Le Thomas, T. Naas, A. Karim, and P. Nordmann. 2000. Bio-
chemical sequence analyses of GES-1, a novel class A extended-spectrum

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␤-lactamase, and the class 1 integron In52 from Klebsiella pneumoniae. Anti-
microb. Agents Chemother. 44:622–632.
REFERENCES 6. Poirel, L., G. F. Weldhagen, T. Naas, C. De Champs, M. G. Dove, and P.
1. Collis, C. M., and R. M. Hall. 1995. Expression of antibiotic resistance genes Nordmann. 2001. GES-2, a class A ␤-lactamase from Pseudomonas aeruginosa
with increased hydrolysis of imipenem. Antimicrob. Agents Chemother.
in the integrated cassettes of integrons. Antimicrob. Agents Chemother. 39:
45:2598–2603.
155–162.
Mariana Castanheira
Rodrigo E. Mendes
Timothy R. Walsh*
Department of Pathology & Microbiology
University of Bristol
Bristol, United Kingdom

Ana C. Gales
Disciplina de Doencas Infecciosas e Parasitarias
Universidade Federal de Sao Paulo
Sao Paulo, Brazil

Ronald N. Jones
The JONES Group/JMI Laboratories
North Liberty, Iowa

*Phone: 44 117 928-7522

Fax: 44 117 928-7896
E-mail: t.r.walsh@bristol.ac.uk