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Antimicrob Agents Chemother. 2010 July; 54(7): 3072.
Published online 2010 April 26. doi:  10.1128/AAC.00513-10
PMCID: PMC2897310

Emergence of KPC-Producing Pseudomonas aeruginosa in the United States [down-pointing small open triangle]

Laurent Poirel, Patrice Nordmann,* and Emilie Lagrutta
Service de Bactériologie-Virologie
INSERM U914 “Emerging Resistance to Antibiotics”
Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris
Faculté de Médecine et Université Paris-Sud
Kremlin-Bicêtre, France
Timothy Cleary
Department of Pathology
University of Miami, Jackson Memorial Hospital
Miami, Florida 33136-1096

Recent years have shown the emergence and dissemination of isolates of Enterobacteriaceae producing carbapenemases in different parts of the world (3). In many cases, those carbapenemases were KPC β-lactamases (5). Those enzymes hydrolyze all β-lactams, including carbapenems at a significant level, with the exception of cephamycins. The blaKPC-like genes have been reported most often from enterobacterial species (mostly Klebsiella pneumoniae species) recovered from several states in the United States (5). Besides the United States, KPC-producing K. pneumoniae isolates are found to be endemic in Greece and Israel, and there are, in addition, scattered reports from all over the world, including Western Europe, China, and South and Central America (5). In Colombia, the first identification of KPC-2-positive Pseudomonas aeruginosa isolates has been reported (6). We describe here the first identification of a KPC-producing P. aeruginosa isolate now in the United States.

In October 2009, a 68-year-old African-American man with history of diabetes and hypertension was admitted with a myocardial infarction to a 1,500-bed teaching hospital in south Florida. Mechanical ventilation was required upon admission to the medical intensive care unit. He did not report any recent history of hospitalization or travel. The patient received an empirical antibiotic therapy consisting of ceftriaxone and vancomycin. Four weeks after admission, he developed hypothermia and blood and urine cultures grew P. aeruginosa. The patient subsequently received an empirical therapy based on meropenem. MICs of the P. aeruginosa P13 isolate measured by the Etest method (AB Biodisk, Solna, Sweden) and interpreted according to CLSI standards showed multidrug resistance including resistance to all carbapenems (carbapenem MICs of >256 μg/ml) (2). That isolate remained susceptible only to amikacin, gentamicin, and colistin. Consequently, the therapy was based on colistin and amikacin, and his subsequent blood cultures remained negative.

Molecular investigations were then performed on this isolate. PCR primers were used for the detection of Ambler class A and class B β-lactamase genes, followed by sequencing, which identified the blaKPC-2 β-lactamase gene coding for carbapenemase KPC-2 (8). Analysis of the plasmid content of P. aeruginosa isolate 13 identified a single plasmid of ca. 66 kb that was successfully transferred to Escherichia coli by electroporation, with a selection performed on amoxicillin (100 μg/ml)-containing agar plates. The E. coli transformants expressing KPC-2 showed a 3-fold increase of MICs for imipenem, meropenem, and ertapenem, but they did not show any additional non-β-lactam resistance. PCR mapping performed as described previously (3) showed that the blaKPC-2 gene was part of the Tn4401b transposon originally identified from a K. pneumoniae isolate from New York (4) and also identified from the clonally related Colombian P. aeruginosa isolates (6). Pulsed-field gel electrophoresis (PFGE) performed as described previously, however, indicated that P. aeruginosa isolate P13 was clonally unrelated to P. aeruginosa PA2404 from Colombia (data not shown).

This is the first identification of a KPC-producing P. aeruginosa isolate in the United States. It is noteworthy that it did not correspond to an imported case. It therefore remains to be evaluated to what extent KPC-type enzymes have spread in P. aeruginosa in the United States, since the phenotypic detection of production of that carbapenemase remains impossible. Use of molecular techniques only may allow determination of to what extent diffusion of such a blaKPC gene may contribute to the emergence of multidrug-resistant P. aeruginosa isolates in the United States. Taking in account the recent identification of KPC-positive P. aeruginosa isolates in South America and Caribbean islands (1, 7) and the importance of immigration from these countries to the United States, it is very likely that this resistance determinant has already spread widely.

Acknowledgments

This work was mostly funded by the INSERM, France, and by grants from the Ministère de l'Education Nationale et de la Recherche (UPRES-EA3539), Université Paris XI, France, and the European Community (TROCAR, HEALTH-F3-2008-223031, and TEMPOtest-QC, HEALTH-2009-241742).

We thank M. V. Villegas for the gift of P. aeruginosa PA2404.

Footnotes

[down-pointing small open triangle]Published ahead of print on 26 April 2010.

REFERENCES

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